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Sample records for brazil presenting mutations

  1. Present situation of refractories in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Bittencourt, P. (Magnesita S.A., (Brazil))

    1992-11-10

    This paper outlines the present situation of refractories in Brazil, particularly the use of refractories in the steel industry which is one of the major industries in this country. Brazil is the 8th largest steel producer in the world, and about 64% of all the production is exported. Because of increasing competitions in the world market, high-level production techniques are required, and active improvements of refractories are also being carried out. The specific consumption of refractories in 1 ton of steel has gradually decreased to produce high-quality refractories. In Brazil, 95% of all demand except for special items such as submerged nozzles and blast furnace carbon blocks can be provided domestically. It is characteristic that raw materials for refractories, such as magnesite, bauxite, and graphite can also be self-supporting. Compositions and physical properties of typical refractories used for various purposes in iron and steel manufactures including blast furnaces, torpedo cars, BOF converters, electric are furnaces, and electric arc ladles are described, and the direction toward their conversion into new materials is shown. Moreover, the trends of refractories for the cement industry and for nonferrous metals such as aluminum are introduced. 6 figs., 15 tabs.

  2. Mutational Profile of Homozygous β-Thalassemia in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Carrocini, Gisele C S; Venancio, Larissa P R; Pessoa, Viviani L R; Lobo, Clarisse L C; Bonini-Domingos, Claudia R

    2017-01-01

    β-Thalassemia (β-thal) is a hemolytic anemia that is caused by point mutations in most cases. The Brazilian population is highly heterogeneous and knowledge of the mutations that make up the genotypic profile of individuals can contribute information about the formation of the population and clinical condition of patients. In this study, we evaluated the mutations present in homozygous β-thal patients from Rio de Janeiro, Brazil. We analyzed 24 samples of peripheral blood of patients with homozygous β-thal. To identify the mutations, we carried out allele-specific-polymerase chain reaction (AS-PCR) and DNA sequencing. We found 11 different mutations on the β-globin gene. Among the most frequent mutations observed were HBB: c.92 + 6T>C, followed by HBB: c.93-21G>A, HBB: c.118C>T and HBB: c.92 + 1G>A. We also identified the rare mutation HBB: c.75T>A that was reported in an individual carrying Hb S (HBB: c.20A>T)/β-thal (HBB: c.75T>A) but not in Brazilian thalassemic patients, thus, this is the first report of this mutation in Brazilian β-thal patients. For its multiethnic character, Brazil has different mutations that cause β-thal and that are distributed with different frequencies according to the regions of the country. Our findings contribute to the description of the mutational profile of Brazilian thalassemic patients, showing wide heterogeneity and genetic variability.

  3. The Lebanese mutation as an important cause of familial hypercholesterolemia in Brazil

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    F.L. Alberto

    1999-06-01

    Full Text Available Familial hypercholesterolemia (FH is a common autosomal disorder that affects about one in 500 individuals in most Western populations and is caused by a defect in the low-density-lipoprotein receptor (LDLr gene. In this report we determined the molecular basis of FH in 59 patients from 31 unrelated Brazilian families. All patients were screened for the Lebanese mutation, gross abnormalities of the LDLr gene, and the point mutation in the codon 3500 of the apolipoprotein B-100 gene. None of the 59 patients presented the apoB-3500 mutation, suggesting that familial defective ApoB-100 (FDB is not a major cause of inherited hypercholesterolemia in Brazil. A novel 4-kb deletion in the LDLr gene, spanning from intron 12 to intron 14, was characterized in one family. Both 5' and 3' breakpoint regions were located within Alu repetitive sequences, which are probably involved in the crossing over that generated this rearrangement. The Lebanese mutation was detected in 9 of the 31 families, always associated with Arab ancestry. Two different LDLr gene haplotypes were demonstrated in association with the Lebanese mutation. Our results suggest the importance of the Lebanese mutation as a cause of FH in Brazil and by analogy the same feature may be expected in other countries with a large Arab population, such as North American and Western European countries.

  4. Childhood presentation of COL4A1 mutations

    NARCIS (Netherlands)

    Shah, S.; Ellard, S.; Kneen, R.; Lim, M.; Osborne, N.; Rankin, J.; Stoodley, N.; van der Knaap, M.S.; Whitney, A.; Jardine, P.

    2012-01-01

    Aim To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. Method We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family

  5. Childhood presentation of COL4A1 mutations

    NARCIS (Netherlands)

    Shah, Siddharth; Ellard, Sian; Kneen, Rachel; Lim, Ming; Osborne, Nigel; Rankin, Julia; Stoodley, Neil; van der Knaap, Marjo; Whitney, Andrea; Jardine, Philip

    2012-01-01

    To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were

  6. Characterization of beta-thalassemia mutations in patients from the state of Rio Grande do Norte, Brazil

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    Zama Messala Luna da Silveira

    2011-01-01

    Full Text Available 35 unrelated individuals were studied for characterization as either heterozygous or homozygous for beta-thalassemia. Molecular analysis was done by PCR/RFLP to detect the mutations most commonly associated with beta-thalassemia (β0IVS-I-1, β+IVS-I-6, and β039. In the patients who showed none of these mutations, the beta-globin genes were sequenced. Of the 31 heterozygous patients, 13 (41.9% had the β+IVS-I-6 mutation, 15 (48.4% the β0IVS-I-1 mutation, 2 (6.5% the β+IVS-I-110 mutation and 1 (3.2% the β+IVS-I-5 mutation. IVS-I-6 was detected in the four homozygotes. The mutation in codon 39, often found in previous studies in Brazil, was not detected in the present case. This is the first study aiming at identifying mutations that determine beta-thalassemia in the state of Rio Grande do Norte.

  7. Clinical presentation and mutations in Danish patients with Wilson disease

    DEFF Research Database (Denmark)

    Møller, Lisbeth Birk; Horn, Nina; Jeppesen, Tina Dysgaard

    2011-01-01

    consistently indicative of WND, with the exception of the 24-h urine-Cu test, which is always outside the normal range. Mutations were identified in 100% of the screened ATP7B alleles (70 unrelated), including five novel mutations: p.1021K; p.G1158V; p.L1304F; IVS20-2A>G; Ex5_6del. In all, 70% of mutations...... were found in exons 8, 14, 17, 18, and 20. The most frequent mutation, p.H1069Q, comprised 18%. We propose a new and simple model that correlates genotype and age of onset. By assuming that the milder of two mutations is 'functionally dominant' and determines the age of onset, we classified 25....../27 mutations as either severe (age of onset 20 years), and correctly predicted the age of onset in 37/39 patients. This method should be tested in other Wilson populations....

  8. BRAF and KIT somatic mutations are present in amelanotic melanoma.

    Science.gov (United States)

    Massi, Daniela; Pinzani, Pamela; Simi, Lisa; Salvianti, Francesca; De Giorgi, Vincenzo; Pizzichetta, Maria A; Mirri, Francesco; Steffan, Agostino; Orlando, Claudio; Santucci, Marco; Canzonieri, Vincenzo

    2013-10-01

    The genotypic profile of rare amelanotic melanomas (AMs) has been poorly investigated, thus preventing either an accurate identification as a distinctive melanoma subtype or therapy stratification. Here, we investigated the presence of the BRAF(V600E) mutation by real-time quantitative PCR and KIT mutations (exons 11 and 17) by sequencing analysis in 33 AMs. AMs included 'truly' amelanotic lesions (n = 19), with no melanin pigmentation upon dermoscopic inspection and hypomelanotic lesions (n = 14), by definition partially pigmented lesions showing a melanin pigmentation area of less than 25% of the total surface area. The frequency of the BRAF(V600E) mutation was 70.3% in the 33 cases, a percentage that increased to 89% when only the subgroup of thin melanomas (≤ 1 mm in thickness, n = 9) was considered. KIT mutations were found in 12.1% of AMs, all of which developed in nonacral sites. The identification of a relatively high frequency of BRAF(V600E) and KIT mutations in AMs may have important consequences for implementation of the novel targeted therapies now available to treat this life-threatening disease.

  9. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients.

    Science.gov (United States)

    Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; Reis, Vitor Manoel Silva dos

    2013-01-01

    Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients.

  10. Plasmid-mediated quinolone resistance (PMQR) and mutations in the topoisomerase genes of Salmonella enterica strains from Brazil.

    Science.gov (United States)

    Ferrari, Rafaela; Galiana, Antonio; Cremades, Rosa; Rodríguez, Juan Carlos; Magnani, Marciane; Tognim, M C B; Oliveira, Tereza C R M; Royo, Gloria

    2013-01-01

    The objective of this study was to identify mutations in the Quinolone Resistance Determining sources Regions (QRDR) of the gyrA, gyrB, parC, and parE genes and to determine if any of the qnr variants or the aac(6')-Ib-cr variant were present in strains of Salmonella spp. isolated in Brazil. A total of 126 Salmonella spp. strains from epidemic (n = 114) and poultry (n = 12) origin were evaluated. One hundred and twelve strains (88.8%) were resistant to nalidixic acid (NAL) and 29 (23.01%) showed a reduced susceptibility to ciprofloxacin (Cip). The mutations identified were substitutions limited to the QRDR of the gyrA gene in the codons for Serine 83, Aspartate 87 and Alanine 131. The sensitivity to NAL seems to be a good phenotypic indication of distinguishing mutated and non-mutated strains in the QRDR, however the double mutation in gyrA did not cause resistance to ciprofloxacin. The qnrA1 and qnrB19 genes were detected, respectively, in one epidemic strain of S. Enteritidis and one strain of S. Corvallis of poultry origin. Despite previous detection of qnr genes in Brazil, this is the first report of qnr gene detection in Salmonella, and also the first detection of qnrB19 gene in this country. The results alert for the continuous monitoring of quinolone resistance determinants in order to minimize the emergence and selection of Salmonella spp. strains showing reduced susceptibility or resistance to quinolones.

  11. Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

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    N. Magdalena

    2005-05-01

    Full Text Available Fanconi anemia (FA is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30% FA patients studied. Thirteen of the 80 (16.25% were homozygotes and 11 of the 80 (13.75% were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

  12. Prevalence and molecular characterization of β-thalassemia in the state of Bahia, Brazil: first identification of mutation HBB: c.135delC in Brazil.

    Science.gov (United States)

    Fonseca, Silvana F; Moura Neto, Jose P; Goncalves, Marilda S

    2013-01-01

    β-Thalassemia (β-thal) is a hereditary disease with at least 200 known causative molecular defects, with a limited number of distinct mutations predominating in any given population. The Brazilian population is one of the most heterogeneous in the world. Although occurrences of β-thal in this country have been recognized for a long time and previous studies have shown important regional differences related to the mutational profile, no extensive analysis of mutations of the HBB gene has been carried out in Brazil. We examined 1011 teenagers from Bahia, a state located in the northeast of Brazil. Hematological data were obtained using automated cell counting, hemoglobin (Hb) profiles were studied by high performance liquid chromatography (HPLC), and DNA was analyzed by automated sequencing. None of the four Mediterranean mutations that are most frequently found in South and Southeast Brazil (HBB: c.118C>T; HBB: c.93-21G>A; HBB: c.92+1G>A; HBB: c.92+6T>C), was found to be responsible for thalassemia in the cases that we studied. One heterozygote for a frameshift mutation at codon 44 (-C) was identified. This is the first study to determine the prevalence and profile of β-thal in Bahia State. For the first time in Brazil, we report the occurrence of the HBB: c.135delC mutation in the β-globin gene.

  13. Plasmid-mediated quinolone resistance (PMQR and mutations in the topoisomerase genes of Salmonella enterica strains from Brazil

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    Rafaela Ferrari

    2013-01-01

    Full Text Available The objective of this study was to identify mutations in the Quinolone Resistance Determining sources Regions (QRDR of the gyrA, gyrB, parC, and parE genes and to determine if any of the qnr variants or the aac(6'-Ib-cr variant were present in strains of Salmonella spp. isolated in Brazil. A total of 126 Salmonella spp. strains from epidemic (n = 114 and poultry (n = 12 origin were evaluated. One hundred and twelve strains (88.8% were resistant to nalidixic acid (NAL and 29 (23.01% showed a reduced susceptibility to ciprofloxacin (Cip. The mutations identified were substitutions limited to the QRDR of the gyrA gene in the codons for Serine 83, Aspartate 87 and Alanine 131. The sensitivity to NAL seems to be a good phenotypic indication of distinguishing mutated and nonmutated strains in the QRDR, however the double mutation in gyrA did not cause resistance to ciprofloxacin. The qnrA1 and qnrB19 genes were detected, respectively, in one epidemic strain of S. Enteritidis and one strain of S. Corvallis of poultry origin. Despite previous detection of qnr genes in Brazil, this is the first report of qnr gene detection in Salmonella, and also the first detection of qnrB19 gene in this country. The results alert for the continuous monitoring of quinolone resistance determinants in order to minimize the emergence and selection of Salmonella spp. strains showing reduced susceptibility or resistance to quinolones.

  14. Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

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    Srivastava Kumar

    2008-12-01

    Full Text Available Abstract Background The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. Methods We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. Results The R337H mutation was found in three patients but in none of the controls (p = 0.0442. Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16 and MDM2 (SNP309 genes that may further diminish TP53 tumor suppressor activity. Conclusion These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility.

  15. First report of the Phe1534Cys kdr mutation in natural populations of Aedes albopictus from Brazil.

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    Aguirre-Obando, Oscar Alexander; Martins, Ademir Jesus; Navarro-Silva, Mário Antônio

    2017-03-27

    Knockdown resistance (kdr), caused by alterations in the voltage-gated sodium channel (NaV), is one of the mechanisms responsible for pyrethroid (PY) resistance. In the Asian tiger mosquito, Aedes albopictus, at least four different mutations were described in the IIIS6 NaV segment in populations from Asia, North America and Europe. In contrast, in Aedes aegypti at least 12 non-synonymous mutations have been reported at nine different codons, mostly in the IIS6 and IIIS6 NaV segments. The Phe1534Cys kdr mutation in the IIIS6 NaV segment is the most prevalent in populations of Ae. aegypti worldwide, also found in Ae. albopictus from Singapore. Herein, we investigated the DNA diversity corresponding to the IIS6 and IIIS6 NaV segments in natural populations of Ae. albopictus from Brazil. DNA from eight Brazilian Ae. albopictus natural populations were individually extracted and pooled by states of origin, amplified, cloned and sequenced for the corresponding IIS6 and IIIS6 NaV segments. Additionally, samples from each location were individually genotyped by an allelic specific PCR (AS-PCR) approach to obtain the genotypic and allelic frequencies for the 1534 NaV site. No non-synonymous substitutions were observed in the IIS6 sequences. However, the Phe1534Cys kdr mutation was evidenced in the Ae. albopictus NaV IIIS6 segment sequences from Paraná (PR) and Rondônia (RO) states, but not from Mato Grosso (MT) state. The 1534Cys (kdr) allele varied from 3% (Marilena/PR and Porto Velho/RO) to 10% (Foz do Iguaçu/PR). To our knowledge, this paper reports the first occurrence and provides distribution data of a possible kdr mutation in Ae. albopictus in South America. The emergence of a likely kdr mutation in Ae. albopitus natural populations is a signal of alert for vector control measures since PY are the most popular insecticides adopted by residents. Additionally, once the kdr allele is present, its frequency tends to increase faster under exposition to those compounds

  16. Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome.

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    Woloszynek, Jill R; Rothbaum, Robert J; Rawls, Amy S; Minx, Patrick J; Wilson, Richard K; Mason, Philip J; Bessler, Monica; Link, Daniel C

    2004-12-01

    Shwachman-Diamond Syndrome (SDS) is a rare multisystem disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and metaphyseal chondrodysplasia. Recent studies show that mutations of SBDS, a gene of unknown function, are present in the majority of patients with SDS. In the present study, we show that most, but not all, patients classified based on rigorous clinical criteria as having SDS had compound heterozygous mutations of SBDS. Full-length SBDS protein was not detected in leukocytes of SDS patients with the most common SBDS mutations, consistent with a loss-of-function mechanism. In contrast, SBDS protein was expressed at normal levels in SDS patients without SBDS mutations. These data confirm the absence of SBDS mutations in this subgroup of patients and suggest that SDS is a genetically heterogeneous disorder. The presence (or absence) of SBDS mutations may define subgroups of patients with SDS who share distinct clinical features or natural history.

  17. Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.

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    Chaves, R G; Pereira, L da Veiga; de Araújo, F T; Rozenberg, R; Carvalho, M D F; Coelho, J C; Michelin-Tirelli, K; Chaves, M de Freitas; Cavalcanti, G B

    2015-10-01

    Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Escherichia coli Mutators Present an Enhanced Risk for Emergence of Antibiotic Resistance during Urinary Tract Infections

    OpenAIRE

    Miller, Keith; O'Neill, Alexander John; Chopra, Ian

    2004-01-01

    Mutators may present an enhanced risk for the emergence of antibiotic resistance in bacteria during chemotherapy. Using Escherichia coli mutators as a model, we evaluated their ability to develop resistance to antibiotics routinely used for the treatment of urinary tract infections (UTIs). Under conditions that simulate therapeutic drug concentrations in humans, low-level resistance to trimethoprim, gentamicin, and cefotaxime emerged more frequently in mutators than normal strains. Resistance...

  19. Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations.

    Science.gov (United States)

    Garcia, Daniel F; Camelo, José S; Molfetta, Greice A; Turcato, Marlene; Souza, Carolina F M; Porta, Gilda; Steiner, Carlos E; Silva, Wilson A

    2016-05-12

    Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of different mutations described in the GALT gene, some of them specific to certain populations, reflecting consequence of founder effect. This study reviews the main clinical findings and depicts the spectrum of mutations identified in 19 patients with CG, six with Duarte Galactosemia and one with type 2 Galactosemia in Brazil. Some individuals were diagnosed through expanded newborn screening test, which is not available routinely to all newborns. The main classical Galactosemia mutations reported to date were identified in this study, as well as the Duarte variant and seven novel mutations - c.2 T > C (p.M1T), c.97C > A (p.R33S), c.217C > T (p.P73S), c.328 + 1G > A (IVS3 + 1G > A), c.377 + 4A > C (IVS4 + 4A > C), c.287_289delACA (p.N97del) and c.506A > C (p.Q169P). This was expected, given the high miscegenation of the Brazilian population. This study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs.

  20. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients

    OpenAIRE

    Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; ABRANTES-LEMOS, Clarice Pires; Cançado,Eduardo Luiz Rachid; Reis,Vitor Manoel Silva dos

    2013-01-01

    BACKGROUND: Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES: Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors...

  1. Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.

    Science.gov (United States)

    Bleyer, Anthony J; Kmoch, Stanislav; Antignac, Corinne; Robins, Vicki; Kidd, Kendrah; Kelsoe, John R; Hladik, Gerald; Klemmer, Philip; Knohl, Stephen J; Scheinman, Steven J; Vo, Nam; Santi, Ann; Harris, Alese; Canaday, Omar; Weller, Nelson; Hulick, Peter J; Vogel, Kristen; Rahbari-Oskoui, Frederick F; Tuazon, Jennifer; Deltas, Constantinos; Somers, Douglas; Megarbane, Andre; Kimmel, Paul L; Sperati, C John; Orr-Urtreger, Avi; Ben-Shachar, Shay; Waugh, David A; McGinn, Stella; Bleyer, Anthony J; Hodanová, Katerina; Vylet'al, Petr; Živná, Martina; Hart, Thomas C; Hart, P Suzanne

    2014-03-01

    The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

  2. Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects.

    Science.gov (United States)

    Vaurs-Barrière, Catherine; Deville, Marlène; Sarret, Catherine; Giraud, Geneviève; Des Portes, Vincent; Prats-Viñas, José-Maria; De Michele, Giuseppe; Dan, Bernard; Brady, Angela F; Boespflug-Tanguy, Odile; Touraine, Renaud

    2009-01-01

    Pelizaeus-Merzbacher Disease is an X-linked hypomyelinatiing leukodystrophy. We report mutations in the thyroid hormone transporter gene MCT8 in 11% of 53 families affected by hypomyelinating leukodystrophies of unknown aetiology. The 12 MCT8 mutated patients express initially a Pelizaeus-Merzbacher-Like disease phenotype with a latter unusual improvement of magnetic resonance imaging white matter signal despite absence of clinical progression. This observation underlines the interest of determining both free T3 and free T4 serum concentrations to screen for MCT8 mutations in young patients (<3 y) with a severe Pelizaeus-Merzbacher-Like disease presentation or older severe mentally retarded male patients with "hypomyelinated" regions.

  3. Characterization of a Hepatitis B virus strain in southwestern Paraná, Brazil, presenting mutations previously associated with anti-HBs Resistance Caracterização de uma cepa de hepatite por vírus B no sudoeste do Paraná, Brasil, apresentando mutações previamente associadas à resistência anti-HBs

    Directory of Open Access Journals (Sweden)

    Dennis Armando Bertolini

    2010-02-01

    Full Text Available The present study investigated if hepatitis B virus (HBV mutants circulate in the southwestern region of the State of Paraná, Brazil, by analyzing samples from children who received immunoprophylaxis but were born to HBV carrier mothers. Samples from 25 children were screened for HBV serum markers and for HBV DNA by PCR. Only one sample was positive for HBsAg, anti-HBs and HBV DNA, although the child had been vaccinated. Analysis of the S gene sequence of this sample showed the presence of a proline at position 105, a serine at position 114, three threonines at positions 115, 116 and 140, and a glutamine at position 129. The presence of these amino acids, except for serine at position 114, has been related to monoclonal or polyclonal therapy with anti-HBs after liver transplantation, whereas the presence of threonine at position 116 has been described in immunized children from Singapore. This finding demonstrates the possible circulation of HBV strains resistant to hepatitis B immunoprophylaxis in southwestern Paraná, Brazil. The genotype of the sample was identified as genotype D, which is frequently found in the region studied. Since 36% of the children had received incomplete or no immunoprophylaxis, more extensive follow-up of children born to HBsAg-positive mothers is needed.O presente estudo investigou se mutantes do vírus da hepatite B (HBV circulam na região Sudoeste do Estado do Paraná, Brasil, analisando amostras de crianças que receberam a imunoprofilaxia por terem nascido de mães portadoras do HBV. Amostras de 25 crianças foram analisadas para os marcadores sorológicos do HBV e para o DNA-HBV por PCR. Somente uma amostra foi positiva para AgHBs, anti-HBs e DNA-HBV, apesar da criança ter sido vacinada. Análises da seqüência do gene S desta amostra mostrou a presença de uma prolina na posição 105, uma serina na posição 114, três treoninas nas posições 115, 116 e 140, e uma glutamina na posição 129. A presen

  4. Curriculum Studies in Brazil: Intellectual Histories, Present Circumstances. International and Development Education

    Science.gov (United States)

    Pinar, William F., Ed.

    2011-01-01

    This collection, comprised of chapters focused on the intellectual histories and present circumstances of curriculum studies in Brazil, is Pinar's summary of exchanges (occurring over a two-year period) between the authors and members of an International Panel (scholars working in Finland, South Africa, the United States). From these and the…

  5. PROP1 gene mutations in a 36-year-old female presenting with psychosis

    Directory of Open Access Journals (Sweden)

    Durgesh Prasad Chaudhary

    2017-03-01

    Full Text Available Combined pituitary hormonal deficiency (CPHD is a rare disease that results from mutations in genes coding for transcription factors that regulate the differentiation of pituitary cells. PROP1 gene mutations are one of the etiological diagnoses of congenital panhypopituitarism, however symptoms vary depending on phenotypic expression. We present a case of psychosis in a 36-year-old female with congenital panhypopituitarism who presented with paranoia, flat affect and ideas of reference without a delirious mental state, which resolved with hormone replacement and antipsychotics. Further evaluation revealed that she had a homozygous mutation of PROP1 gene. In summary, compliance with hormonal therapy for patients with hypopituitarism appears to be effective for the prevention and treatment of acute psychosis symptoms.

  6. Wilson's disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene

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    Ricardo Schmitt de Bem

    2013-08-01

    Full Text Available OBJECTIVE: Wilson's disease (WD is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1% followed by the c.3402delC at exon 15 (allelic frequency=11.4%. The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

  7. Prospective study of POLG mutations presenting in children with intractable epilepsy: prevalence and clinical features.

    Science.gov (United States)

    Uusimaa, Johanna; Gowda, Vasantha; McShane, Anthony; Smith, Conrad; Evans, Julie; Shrier, Annie; Narasimhan, Manisha; O'Rourke, Anthony; Rajabally, Yusuf; Hedderly, Tammy; Cowan, Frances; Fratter, Carl; Poulton, Joanna

    2013-06-01

    To assess the frequency and clinical features of childhood-onset intractable epilepsy caused by the most common mutations in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma. Children presenting with nonsyndromic intractable epilepsy of unknown etiology but without documented liver dysfunction at presentation were eligible for this prospective, population-based study. Blood samples were analyzed for the three most common POLG mutations. If any of the three tested mutations were found, all the exons and the exon-intron boundaries of the POLG gene were sequenced. In addition, we retrospectively reviewed the notes of patients presenting with intractable epilepsy in which we had found POLG mutations. All available clinical data were collected by questionnaire and by reviewing the medical records. We analyzed 213 blood DNA samples from patients fulfilling the inclusion criteria of the prospective study. Among these, five patients (2.3%) were found with one of the three common POLG mutations as homozygous or compound heterozygous states. In addition, three patients were retrospectively identified. Seven of the eight patients had either raised cerebrospinal fluid (CSF) lactate (n = 3) or brain magnetic resonance imaging (MRI) changes (n = 4) at presentation with intractable epilepsy. Three patients later developed liver dysfunction, progressing to fatal liver failure in two without previous treatment with sodium valproate (VPA). Furthermore, it is worth mentioning that one patient presented first with an autism spectrum disorder before seizures emerged. Mutations in POLG are an important cause of early and juvenile onset nonsyndromic intractable epilepsy with highly variable associated manifestations including autistic features. This study emphasizes that genetic testing for POLG mutations in patients with nonsyndromic intractable epilepsies is very important for clinical diagnostics, genetic counseling, and treatment decisions

  8. Novel mutation in the ATL1 with autosomal dominant hereditary spastic paraplegia presented as dysautonomia.

    Science.gov (United States)

    Shin, Jung-Won; Jung, Keun-Hwa; Lee, Soon-Tae; Moon, Jangsup; Seong, Moon-Woo; Park, Sung Sup; Lee, Sang Kun; Chu, Kon

    2014-10-01

    SPG3A, which is the second most common type of autosomal dominant hereditary spastic paraplegia (HSP), is caused by mutations in the atlastin GTPase 1 gene, ATL1. We report a case of a patient who presented as dysautonomia and had a novel splicing mutation c.35-3C>T in exon 2 of the ATL1. Orthostatic intolerance, urinary symptoms, hyperreflexia in the biceps and knee jerk, and decreased proprioception in both limbs were observed on neurological examinations. We tested the autonomic function and performed genetic tests for the SPG4 and SPG3A forms of HSP. This case is a genetically confirmed HSP with a novel mutation in SPG3A, and extends the phenotype of SPG3A. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Clinical presentation and follow up of children with congenital toxoplasmosis in Brazil

    OpenAIRE

    Sáfadi Marco A. P.; Berezin Eitan N.; Farhat Calil K.; Carvalho Eduardo S.

    2003-01-01

    We evaluated the clinical presentation and determined the ocular and neurologic sequelae in children with congenital toxoplasmosis in Brazil, taking into consideration the shortage of national publications on this disease. Follow-up evaluations were made of 43 children with congenital toxoplasmosis referred to Santa Casa de São Paulo, during a period of at least five years. Selection of the cases was based in clinical and laboratory criteria. A clear predominance of children with subclinical ...

  10. AFRICA-BRAZIL RELATIONS DURING THE MILITARY REGIME AND IN THE PRESENT-DAY

    OpenAIRE

    Rosi, Bruno Gonçalves; Universidade Candido Mendes

    2011-01-01

    This article examines the political and commercial relations between Brazil and Africa on two periods, the military regime and the present, aiming to briefly examine both and explore points of contact and current perspectives of the African policy. Este artigo analisa as relações politico-comerciais Brasil-África em dois momentos, o regime militar e a atualidade, procurando analisar brevemente ambos e explorar pontos de contato e perspectivas atuais da política africana.

  11. A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia

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    Tonyushkina Ksenia N

    2012-05-01

    Full Text Available Abstract Background Familial Hypocalciuric Hypercalcemia (FHH is a generally benign disorder caused by heterozygous inactivating mutations in the Calcium-Sensing Receptor (CaSR gene resulting in altered calcium metabolism. Objective We report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia. Case overview A female infant was admitted at 2 weeks of age for suspected non-accidental trauma (NAT. Laboratory testing revealed hypercalcemia (3.08 mmol/L, elevated iPTH (20.4 pmol/L and low urinary calcium clearance (0.0004. Radiographs demonstrated multiple healing metaphyseal and rib fractures and bilateral femoral bowing. The femoral deformity and stage of healing were consistent with prenatal injuries rather than non-accidental trauma (NAT. Treatment was initiated with cholecalciferol, 400 IU/day, and by 6 weeks of age, iPTH levels had decreased into the high-normal range. Follow up radiographs demonstrated marked improvement of bone lesions by 3 months. A CaSR gene mutation study showed heterozygosity for a T>C nucleotide substitution at c.1664 in exon 6, resulting in amino acid change I555T in the extracellular domain consistent with a missense mutation. Her mother does not carry the mutation and the father is unknown. At 18 months of age, the child continues to have relative hyperparathyroidism and moderate hypercalcemia but is otherwise normal. Conclusion This neonate with intrauterine fractures and demineralization, moderate hypercalcemia and hyperparathyroidism was found to have a novel inactivating missense mutation of the CaSR not detected in her mother. Resolution of bone lesions and reduction of hyperparathyroidism was likely attributable to the natural evolution of the disorder in infancy as well as the mitigating effect of cholecalciferol treatment.

  12. Antimicrobial resistance, integron carriage, and gyrA and gyrB mutations in Pseudomonas aeruginosa isolated from dogs with otitis externa and pyoderma in Brazil.

    Science.gov (United States)

    Arais, Lavicie R; Barbosa, André V; Carvalho, Cristiane A; Cerqueira, Aloysio M F

    2016-04-01

    Pseudomonas aeruginosa is associated with otitis and pyoderma in dogs and is frequently resistant to several antimicrobial drugs. Resistance genes can be carried by integrons with quinolone resistance mainly due to mutations in DNA topoisomerases II and IV. To evaluate the antimicrobial susceptibility, integron carriage, and gyrA and gyrB mutations in P. aeruginosa isolates from canine otitis and pyoderma. One hundred and four P. aeruginosa strains isolated from dogs with otitis externa (n = 93) and pyoderma (n = 11). Antimicrobial susceptibility against 16 antibacterial agents was evaluated through agar diffusion tests. Integron carriage, class and gyrA and gyrB mutations were analysed by PCR, restriction fragment length polymorphism (RFLP)-PCR and genetic sequencing assays. Isolates were mostly resistant to enrofloxacin (72.2%) and ticarcillin (59.7%). Lower resistance to ciprofloxacin (7.7%), tobramycin (3.8%) and polymixin B (0.0%) was detected. Ten (9.6%) multidrug-resistant (MDR) strains were detected. Eight (7.7%) strains carried class 1 integrons and this was associated with MDR (three isolates, P ≤ 0.05). Five of the integron-carrying strains exhibited aminoglycoside resistance genes. Mutations of gyrA and gyrB were observed in 10 isolates, seven of them resistant to all fluoroquinolones tested. Enrofloxacin and ticarcilin resistance was widespread in P. aeruginosa isolated from dogs in Brazil. Pseudomonas aeruginosa carrying integrons may present a significant challenge for treatment. © 2016 ESVD and ACVD.

  13. Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil.

    Directory of Open Access Journals (Sweden)

    Dirce Maria Carraro

    Full Text Available Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22% [7 in BRCA1 (13%, 4 in BRCA2 (7% and one in TP53 (2% gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes. Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients.

  14. Congenital Thrombotic Thrombocytopenic Purpura: Atypical Presentation And First ADAMTS 13 Mutation In A Tunisian Child

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    aida borgi

    2013-06-01

    Full Text Available Background: Congenital deficiency of ADAMTS13 is characterized by systemic platelet clumping, hemolytic anemia and multiorgan failure. Although, more than 100 mutations have been reported, atypical clinical presentation may be involved in diagnostic difficulties. Case report: A 2 year old Tunisian child presented with chronic thrombopenic purpura which failed to respond to corticosteroids. Hemolytic anemia with schizocytes, occurred ten months later, with no previous history of diarrhea or any neurological abnormality.  Renal function, coagulation screening tests and complement assay were normal. The count of platelet improved after fresh frozen infusion (FFP. Extensive investigations revealed a severe deficiency of ADAMTS 13 activity (level< 5%. Gene sequencing identified mutation in exon 18 of ADAMTS 13 gene. Prophylactic regimen with regular infusions of FFP was associated to favorable outcome. Conclusion: Early ADAMTS 13 activity testing and gene sequencing associated to precocious plasmatherapy are crucial to reduce morbidity and mortality of congenital TTP.

  15. Mutational Analysis in Pediatric Thyroid Cancer and Correlations with Age, Ethnicity, and Clinical Presentation.

    Science.gov (United States)

    Nikita, Maria Eleni; Jiang, Wen; Cheng, Shih-Min; Hantash, Feras M; McPhaul, Michael J; Newbury, Robert O; Phillips, Susan A; Reitz, Richard E; Waldman, Frederic M; Newfield, Ron S

    2016-02-01

    Well-differentiated thyroid cancer (WDTC) incidence in pediatrics is rising, most being papillary thyroid carcinoma (PTC). The objective of the study was to assess the prevalence of different mutations in pediatric WDTC and correlate the genotype with the clinical phenotype. This is a single-center retrospective study. Thyroid tissue blocks from 42 consecutive pediatric WDTC patients who underwent thyroidectomy between 2001 and 2013 were analyzed at Quest Diagnostics for BRAF(V600E), RAS mutations (N,K,H), and RET/PTC and PAX8/PPARγ rearrangements, using validated molecular methods. Thyroid carcinomas included PTC, follicular thyroid carcinoma (FTC), and follicular variant of PTC (FVPTC). Thirty-nine samples (29 females) were genotyped. The mean age at diagnosis was 14.7 years (range 7.9-18.4 years), and most were Hispanic (56.4%) or Caucasian (35.9%). The mean follow-up period was 2.9 years. Mutations were noted in 21/39 (53.8%), with both BRAF(V600E) (n = 9), and RET/PTC (n = 6) detected only in PTC. Mutations were detected in 2/5 FTC (PAX8/PPARγ and NRAS) and 3/6 FVPTC cases (PAX8/PPARγ). Of 28 PTC patients, 57.1% had mutations: 32.1% with BRAF(V600E), 21.4% with RET/PTC, and 3.6% with NRAS. Of patients with BRAF(V600E), 77.8% were Hispanic and 88.9% were >15 years, while all RET/PTC-positive patients were ≤15 years (p = 0.003). Tumor size, lymph node involvement, and distant metastasis at diagnosis (or soon after (131)I ablation) did not vary significantly based on the mutation. BRAF(V600E) was the most common mutation, especially in older and Hispanic adolescents. A larger, ethnically diverse pediatric cohort followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed.

  16. Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.

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    Ruben Attali

    Full Text Available We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+ stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.

  17. Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.

    Science.gov (United States)

    Attali, Ruben; Aharoni, Sharon; Treves, Susan; Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

    2013-01-01

    We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+) stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.

  18. Quaternary ecological and geomorphic changes associated with rainfall events in presently semi-arid northeastern Brazil

    Science.gov (United States)

    Auler, Augusto S.; Wang, Xianfeng; Edwards, R. Lawrence; Cheng, Hai; Cristalli, Patrícia S.; Smart, Peter L.; Richards, David A.

    2004-10-01

    Several geomorphic features and palaeobiotic remains in now semi-arid northeastern Brazil indicate major palaeoenvironmental changes during past periods of increased rainfall. 230Th mass spectrometric ages of speleothems and travertines have allowed the determination of the timing and duration of wetter than present conditions. The data demonstrate that wet events have occurred throughout much of the Pleistocene, present dry conditions having been established at the end of the Younger Dryas. A markedly different fauna comprising megafaunal elements not adapted to the present low arboreal scrubland caatinga vegetation existed in the area. Palaeobotanical remains embedded in travertine indicate forested vegetation at these wetter intervals, suggesting that the caatinga was then replaced or mixed with a semi-deciduous forest. Due to the abundance of travertine sites containing fossil botanical remains in northeastern Brazil, it is believed that forest expansion occurred over large areas of the now semi-arid zone, showing that the long hypothesised forested links between biodiversity-rich Amazon and Atlantic rainforests may indeed have existed during these moister phases. Copyright

  19. Adult Sandhoff disease with 2 mutations in the HEXB gene presenting as brachial amyotrophic diplegia.

    Science.gov (United States)

    Kang, Sa-Yoon; Song, Sook Keun; Lee, Jung Seok; Choi, Jay Chol; Kang, Ji-Hoon

    2013-12-01

    Sandhoff disease is a rare autosomal recessive metabolic disorder of GM2 gangliosides. It is caused by a lack of functional N-acetyl-β-D-glucosaminidase A and B because of mutations in the HEXB gene. We describe a 55-year-old woman with adult Sandhoff disease presenting as brachial amyotrophic diplegia. The assay of total hexosaminidase involving A and B showed decreased level of these activities. Hex-A was 4.6 nmol·min·mL (normal: 7.0-20.0 nmol·min·mL) and Hex-B was 0.1 nmol·min·mL (normal: 1.0-10.0 nmol·min·mL), respectively. Analysis of HEXB gene demonstrated 2 point mutations that were located at the exon 5 (c.619A>G) and exon 11 (c.1250C>T). Compound heterozygosity of these 2 mutations may trigger the development of distinct adult Sandhoff disease phenotype. Sandhoff disease should be considered in the differential diagnosis of lower motor neuron disease, such as brachial amyotrophic diplegia, even if the age at onset is more than 50 years.

  20. Splicing mutation in CYP21 associated with delayed presentation of salt-wasting congenital adrenal hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, B.; Patel, S.V.; Pelczar, J.V. [North Shore Univ. Hospital, Manhasset, NY (United States)] [and others

    1995-07-03

    Patients with salt-wasting congenital adrenal hyperplasia (SW-CAH) most commonly carry an A-G transition at nucleotide 656 (nt 656 A{r_arrow}G), causing abnormal splicing of exons 2 and 3 in CYP21, the gene encoding active steroid 21-hydroxylase. Affected infants are severely deficient in cortisol and aldosterone, and usually come to medical attention during the neonatal period. We report on 2 affected boys, homozygous for the nt 656 mutation, who thrived in early infancy, but suffered salt-wasting crises unusually late in infancy, at 3.5 and 5.5 months, respectively. Laboratory studies at presentation showed hyponatremia, hyperkalemia, dehydration, and acidosis; serum aldosterone was low in spite of markedly elevated plasma renin activity. Basal 17-hydroxyprogesterone levels were only moderately elevated, yet the stimulated levels were more typical of severe, classic CAH due to 21-hydroxylase deficiency. Genomic DNA from the patients was analyzed. Southern blot showed no major deletions or rearrangements. CYP21-specific amplification by polymerase chain reaction, coupled with allele-specific hybridization using wild-type and mutant probes at each of 9 sites for recognized disease-causing mutations, revealed a single, homozygous mutation in each patient: nt 656 A{r_arrow}G. These results were confirmed by sequence analysis. We conclude that the common nt 656 A{r_arrow}G mutation is sometimes associated with delayed phenotypic expression of SW-CAH. We speculate that variable splicing of the mutant CYP21 may modify the clinical manifestation of this disease. 22 refs., 1 fig., 1 tab.

  1. Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome.

    Science.gov (United States)

    Sunga, Annette Y; Ricker, Charité; Espenschied, Carin R; Castillo, Danielle; Melas, Marilena; Herzog, Josef; Bannon, Sarah; Cruz-Correa, Marcia; Lynch, Patrick; Solomon, Ilana; Gruber, Stephen B; Weitzel, Jeffrey N

    2017-04-01

    Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is caused by mismatch repair (MMR) gene mutations. However, data about MMR mutations in Hispanics are limited. This study aims to describe the spectrum of MMR mutations in Hispanics with LS and explore ancestral origins. This case series involved an IRB-approved retrospective chart review of self-identified Hispanic patients (n = 397) seen for genetic cancer risk assessment at four collaborating academic institutions in California, Texas, and Puerto Rico who were evaluated by MMR genotyping and/or tumor analysis. A literature review was conducted for all mutations identified. Of those who underwent clinical genetic testing (n = 176), 71 had MMR gene mutations. Nine mutations were observed more than once. One third (3/9) of recurrent mutations and two additional mutations (seen only once) were previously reported in Spain, confirming the influence of Spanish ancestry on MMR mutations in Hispanic populations. The recurrent mutations identified (n = 9) included both previously reported mutations as well as unique mutations not in the literature. This is the largest report of Hispanic MMR mutations in North America; however, a larger sample and haplotype analyses are needed to better understand recurrent MMR mutations in Hispanic populations. Copyright © 2017. Published by Elsevier Inc.

  2. Determination of thermotolerant coliforms present in coconut water produced and bottled in the Northeast of Brazil

    Directory of Open Access Journals (Sweden)

    Vandbergue Santos Pereira

    2017-10-01

    Full Text Available Abstract Coconut water is considered to be a natural isotonic drink and its marketing is gradually increasing. The objective of the present study was to evaluate the microbiological quality of the coconut water produced and bottled in the Northeast of Brazil. Products form ten industries from different states in the Northeast of Brazil were analyzed. The most probable number (MPN method was used to quantify the coliforms. Samples showing positive for coliforms were seeded on ChromAgar Orient plates and the bacteria identified from isolated colonies using the automated system Vitek 2 (BioMérieux, according to the manufacturer's instructions for the preparation of the inoculum, incubation, reading and interpretation. The samples showed thermotolerant coliform counts between 6.0×102 and 2.6×104 MPN/100 mL. The presence of Klebsiella pneumoniae, Morganella morganii and Providencia alcalifaciens was observed. The implementation of preventive methods and monitoring of the water quality by the industries is required.

  3. Human immunodeficiency virus type 1 (HIV-1 genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy

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    JC Couto-Fernandez

    2005-02-01

    Full Text Available In order to assess the human immunodeficiency virus type 1 (HIV-1 drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation. Viral resistance genotyping was performed using ViroSeqTM Genotyping System (Celera Diagnostic-Abbott, US. The HIV-1 subtyping based on polymerase (pol gene sequences (protease and reverse transcriptase-RT regions was as follows: subtype B (91.2%, subtype F (4.9%, and B/F viral recombinant forms (3.3%. The subtype C was identified in two patients (0.4% and the recombinant CRF_02/AG virus was found infecting one patient (0.2%. The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

  4. Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations

    NARCIS (Netherlands)

    van der Werf, Christine S.; Sribudiani, Yunia; Verheij, Joke B. G. M.; Carroll, Matthew; O'Loughlin, Edward; Chen, Chien-Huan; Brooks, Alice S.; Liszewski, M. Kathryn; Atkinson, John P.; Hofstra, Robert M. W.

    Purpose: Autosomal recessive congenital short bowel syndrome is caused by mutations in CLMP. No mutations were found in the affected males of a family with presumed X-linked congenital short bowel syndrome or in an isolated male patient. Our aim was to identify the disease-causing mutation in these

  5. Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

    OpenAIRE

    Chachá, Silvana Gama Florencio; Gomes-Gouvêa, Michele Soares; Malta, Fernanda de Mello; Ferreira, Sandro da Costa; Villanova, Márcia Guimarães; Souza, Fernanda Fernandes; Teixeira, Andreza Correa; Passos, Afonso Dinis da Costa; Pinho, João Renato Rebello; Martinelli, Ana de Lourdes Candolo

    2017-01-01

    BACKGROUND In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA ...

  6. Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis.

    Directory of Open Access Journals (Sweden)

    Fabiola Traina

    Full Text Available We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM. SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/DNMT3A/ASXL1 mutations independent of KIT (P = 0.04 and sole TET2 mutations (P<0.001. In conclusion, TET2, DNMT3A and ASXL1 mutations are also present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients.

  7. Common variable immune deficiency with mutated TNFSRF13B gene presenting with autoimmune hematologic manifestations

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    Elpis Mantadakis

    2016-10-01

    Full Text Available Patients with common variable immunodeficiency (CVID develop autoimmune hematologic manifestations. We report a 14-year-old boy with Evans syndrome, who presented at the age of 11.5 years with autoimmune hemolysis and was successfully managed with corticosteroids. Initially, the serum immunoglobulins were within the low-normal range for age, but two years after presentation he definitely fulfilled the diagnostic criteria for CVID, despite a negative history for serious infections. DNA sequencing by PCR of the TNFSRF13B gene that encodes the TACI receptor disclosed the heterozygous mutation C104R that is found in approximately 10–15% of patients with CVID. Common variable immunodeficiency should be considered in the differential diagnosis of autoimmune hematologic manifestations, since its timely diagnosis may considerably affect clinical management and patient outcome.

  8. Diabetes Is Associated with Worse Clinical Presentation in Tuberculosis Patients from Brazil: A Retrospective Cohort Study.

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    Leonardo Gil-Santana

    Full Text Available The rising prevalence of diabetes mellitus (DM worldwide, especially in developing countries, and the persistence of tuberculosis (TB as a major public health issue in these same regions, emphasize the importance of investigating this association. Here, we compared the clinical profile and disease outcomes of TB patients with or without coincident DM in a TB reference center in Brazil.We performed a retrospective analysis of a TB patient cohort (treatment naïve of 408 individuals recruited at a TB primary care center in Brazil between 2004 and 2010. Data on diagnosis of TB and DM were used to define the groups. The study groups were compared with regard to TB disease presentation at diagnosis as well as to clinical outcomes such as cure and mortality rates upon anti-tuberculosis therapy (ATT initiation. A composite score utilizing clinical, radiological and microbiological parameters was used to compare TB severity between the groups.DM patients were older than non-diabetic TB patients. In addition, diabetic individuals more frequently presented with cough, night sweats, hemoptysis and malaise than those without DM. The overall pattern of lung lesions assessed by chest radiographic examination was similar between the groups. Compared to non-diabetic patients, those with TB-diabetes exhibited positive acid-fast bacilli in sputum samples more frequently at diagnosis and at 30 days after ATT initiation. Notably, higher values of the TB severity score were significantly associated with TB-diabetes comorbidity after adjustment for confounding factors. Moreover, during ATT, diabetic patients required more frequent transfers to TB reference hospitals for complex clinical management. Nevertheless, overall mortality and cure rates were indistinguishable between the study groups.These findings reinforce the idea that diabetes negatively impacts pulmonary TB severity. Our study argues for the systematic screening for DM in TB reference centers in endemic

  9. PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis

    Science.gov (United States)

    Gall, Emilie Cornec-Le; Audrézet, Marie-Pierre; Renaudineau, Eric; Hourmant, Maryvonne; Charasse, Christophe; Michez, Eric; Frouget, Thierry; Vigneau, Cécile; Dantal, Jacques; Siohan, Pascale; Longuet, Hélène; Gatault, Philippe; Ecotière, Laure; Bridoux, Frank; Mandart, Lise; Hanrotel-Saliou, Catherine; Stanescu, Corina; Depraetre, Pascale; Gie, Sophie; Massad, Michiel; Kersalé, Aude; Séret, Guillaume; Augusto, Jean-François; Saliou, Philippe; Maestri, Sandrine; Chen, Jian-Min; Harris, Peter C.; Férec, Claude; Le Meur, Yannick

    2017-01-01

    Background PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. Study Design Case series, January 2010 to March 2016. Settings & Participants Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. Outcomes Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. Results The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54–0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10–3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%–14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%–81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n = 36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. Limitations Younger patients

  10. Acute myeloid leukaemia with mutated NPM1 presenting with extensive bone marrow necrosis and Charcot-Leyden crystals.

    Science.gov (United States)

    Taylor, Gordon; Ivey, Adam; Milner, Benedict; Grimwade, David; Culligan, Dominic

    2013-09-01

    Here, we report an unusual case of acute myeloid leukaemia with mutated NPM1 presenting with pancytopenia and leukoerythroblastosis, without circulating blasts and bone marrow necrosis with numerous Charcot-Leyden crystals, but no eosinophilia.

  11. Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations

    DEFF Research Database (Denmark)

    Meeths, Marie; Bryceson, Yenan T; Rudd, Eva

    2010-01-01

    Griscelli syndrome type 2 (GS2) is an autosomal-recessive immunodeficiency caused by mutations in RAB27A, clinically characterized by partial albinism and haemophagocytic lymphohistocytosis (HLH). We evaluated the frequency of RAB27A mutations in 21 unrelated patients with haemophagocytic syndromes...... without mutations in familial HLH (FHL) causing genes or an established diagnosis of GS2. In addition, we report three patients with known GS2. Moreover, neurological involvement and RAB27A mutations in previously published patients with genetically verified GS2 are reviewed....

  12. Juvenile-Onset Diabetes and Congenital Cataract: “Double-Gene” Mutations Mimicking a Syndromic Diabetes Presentation

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    Caroline Lenfant

    2017-11-01

    Full Text Available Monogenic forms of diabetes may account for 1–5% of all cases of diabetes, and may occur in the context of syndromic presentations. We investigated the case of a girl affected by insulin-dependent diabetes, diagnosed at 6 years old, associated with congenital cataract. Her consanguineous parents and her four other siblings did not have diabetes or cataract, suggesting a recessive syndrome. Using whole exome sequencing of the affected proband, we identified a heterozygous p.R825Q ABCC8 mutation, located at the exact same amino-acid position as the p.R825W recurring diabetes mutation, hence likely responsible for the diabetes condition, and a homozygous p.G71S mutation in CRYBB1, a gene known to be responsible for congenital cataract. Both mutations were predicted to be damaging and were absent or extremely rare in public databases. Unexpectedly, we found that the mother was also homozygous for the CRYBB1 mutation, and both the mother and one unaffected sibling were heterozygous for the ABCC8 mutation, suggesting incomplete penetrance of both mutations. Incomplete penetrance of ABCC8 mutations is well documented, but this is the first report of an incomplete penetrance of a CRYBB1 mutation, manifesting between susceptible subjects (unaffected mother vs. affected child and to some extent within the patient herself, who had distinct cataract severities in both eyes. Our finding illustrates the importance of family studies to unmask the role of confounding factors such as double-gene mutations and incomplete penetrance that may mimic monogenic syndromes including in the case of strongly evocative family structure with consanguinity.

  13. Clinical presentation and follow up of children with congenital toxoplasmosis in Brazil.

    Science.gov (United States)

    Sáfadi, Marco A P; Berezin, Eitan N; Farhat, Calil K; Carvalho, Eduardo S

    2003-10-01

    We evaluated the clinical presentation and determined the ocular and neurologic sequelae in children with congenital toxoplasmosis in Brazil, taking into consideration the shortage of national publications on this disease. Follow-up evaluations were made of 43 children with congenital toxoplasmosis referred to Santa Casa de São Paulo, during a period of at least five years. Selection of the cases was based in clinical and laboratory criteria. A clear predominance of children with subclinical presentation of the disease at birth (88%) was found. Of the 43 children, 22 (51%) developed neurological manifestations. Using skull radiography, we detected neuroradiologic alterations in seven children (16%) and with tomography in 33 children (77%). Neurological sequelae were identified in 15 children (54%) in the group with cerebral calcifications and in 7 (47%) in the group without cerebral calcifications. We observed chorioretinitis in 95% of the cases. Reactivation of cicatricial lesions and the emergence of new ocular lesions were observed in five cases. The most frequent neurological manifestation was a delay in neuropsychomotor development. Most remarkable was the finding that cerebral calcifications were not associated with a higher incidence of neurological sequelae among the children. Chorioretinitis was the main ocular sequel of the infection, found in nearly all children; it can manifest years from birth, even in children submitted to specific therapy druing the first year of life, highlighting the importance of a follow-up of these children.

  14. Clinical presentation and follow up of children with congenital toxoplasmosis in Brazil

    Directory of Open Access Journals (Sweden)

    Sáfadi Marco A. P.

    2003-01-01

    Full Text Available We evaluated the clinical presentation and determined the ocular and neurologic sequelae in children with congenital toxoplasmosis in Brazil, taking into consideration the shortage of national publications on this disease. Follow-up evaluations were made of 43 children with congenital toxoplasmosis referred to Santa Casa de São Paulo, during a period of at least five years. Selection of the cases was based in clinical and laboratory criteria. A clear predominance of children with subclinical presentation of the disease at birth (88% was found. Of the 43 children, 22 (51% developed neurological manifestations. Using skull radiography, we detected neuroradiologic alterations in seven children (16% and with tomography in 33 children (77%. Neurological sequelae were identified in 15 children (54% in the group with cerebral calcifications and in 7 (47% in the group without cerebral calcifications. We observed chorioretinitis in 95% of the cases. Reactivation of cicatricial lesions and the emergence of new ocular lesions were observed in five cases. The most frequent neurological manifestation was a delay in neuropsychomotor development. Most remarkable was the finding that cerebral calcifications were not associated with a higher incidence of neurological sequelae among the children. Chorioretinitis was the main ocular sequel of the infection, found in nearly all children; it can manifest years from birth, even in children submitted to specific therapy during the first year of life, highlighting the importance of a follow-up of these children.

  15. Clinical presentation and follow up of children with congenital toxoplasmosis in Brazil

    Directory of Open Access Journals (Sweden)

    Marco A. P. Sáfadi

    Full Text Available We evaluated the clinical presentation and determined the ocular and neurologic sequelae in children with congenital toxoplasmosis in Brazil, taking into consideration the shortage of national publications on this disease. Follow-up evaluations were made of 43 children with congenital toxoplasmosis referred to Santa Casa de São Paulo, during a period of at least five years. Selection of the cases was based in clinical and laboratory criteria. A clear predominance of children with subclinical presentation of the disease at birth (88% was found. Of the 43 children, 22 (51% developed neurological manifestations. Using skull radiography, we detected neuroradiologic alterations in seven children (16% and with tomography in 33 children (77%. Neurological sequelae were identified in 15 children (54% in the group with cerebral calcifications and in 7 (47% in the group without cerebral calcifications. We observed chorioretinitis in 95% of the cases. Reactivation of cicatricial lesions and the emergence of new ocular lesions were observed in five cases. The most frequent neurological manifestation was a delay in neuropsychomotor development. Most remarkable was the finding that cerebral calcifications were not associated with a higher incidence of neurological sequelae among the children. Chorioretinitis was the main ocular sequel of the infection, found in nearly all children; it can manifest years from birth, even in children submitted to specific therapy during the first year of life, highlighting the importance of a follow-up of these children.

  16. A case of TUBA1A mutation presenting with lissencephaly and Hirschsprung disease.

    Science.gov (United States)

    Hikita, Norikatsu; Hattori, Hideji; Kato, Mitsuhiro; Sakuma, Satoru; Morotomi, Yoshiki; Ishida, Hiroshi; Seto, Toshiyuki; Tanaka, Katsuji; Shimono, Taro; Shintaku, Haruo; Tokuhara, Daisuke

    2014-02-01

    Gene mutation of tubulin alpha-1A (TUBA1A), a critical component of microtubules of the cytoskeleton, impairs neural migration and causes lissencephaly (LIS). The approximately 45 cases of disease-associated TUBA1A mutations reported to date demonstrate a wide spectrum of phenotypes. Here we describe an 8-year-old girl with lissencephaly, microcephaly, and early-onset epileptic seizures associated with a novel mutation in the TUBA1A gene. The patient developed Hirschsprung disease and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which had not previously been described in TUBA1A mutation-associated disease. Our case provides new insight into the wide spectrum of disease phenotypes associated with TUBA1A mutation. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Sporotrichosis in Rio de Janeiro, Brazil: Sporothrix brasiliensis is associated with atypical clinical presentations.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; de Oliveira, Manoel Marques Evangelista; Freitas, Dayvison Francis Saraiva; do Valle, Antônio Carlos Francesconi; Zancopé-Oliveira, Rosely Maria; Gutierrez-Galhardo, Maria Clara

    2014-09-01

    There have been several recent changes in the taxonomy of Sporothrix schenckii as well as new observations regarding the clinical aspects of sporotrichosis. In this study, we determined the identification of the Sporothrix species associated with both classic and unusual clinical aspects of sporotrichosis observed in the endemic area of sporotrichosis in Rio de Janeiro, Brazil. To verify whether S. brasiliensis is associated with clinical manifestations of sporotrichosis, a cross-sectional study was performed in which Sporothrix isolates from 50 patients with different clinical manifestations were analyzed and their isolates were studied by phenotypic and genotypic methods. Data from these patients revealed a distinct clinical picture and therapeutic response in infections caused by Sporothrix brasiliensis (n = 45) compared to patients with S. schenckii sensu stricto (n = 5). S. brasiliensis was associated with disseminated cutaneous infection without underlying disease, hypersensitivity reactions, and mucosal infection, whereas patients with S. schenckii presented with less severe and more often localized disease, similar to the majority of previously described sporotrichosis cases. Interestingly, S. brasiliensis-infected patients overall required shorter durations of itraconazole (median 16 weeks) compared to the individuals with S. schenckii (median 24 weeks). These findings suggest that Sporothrix species are linked to different clinical manifestations of sporotrichosis and that S. brasiliensis is effectively treated with oral itraconazole.

  18. Sporotrichosis in Rio de Janeiro, Brazil: Sporothrix brasiliensis Is Associated with Atypical Clinical Presentations

    Science.gov (United States)

    Almeida-Paes, Rodrigo; de Oliveira, Manoel Marques Evangelista; Freitas, Dayvison Francis Saraiva; do Valle, Antônio Carlos Francesconi; Zancopé-Oliveira, Rosely Maria; Gutierrez-Galhardo, Maria Clara

    2014-01-01

    Background There have been several recent changes in the taxonomy of Sporothrix schenckii as well as new observations regarding the clinical aspects of sporotrichosis. In this study, we determined the identification of the Sporothrix species associated with both classic and unusual clinical aspects of sporotrichosis observed in the endemic area of sporotrichosis in Rio de Janeiro, Brazil. Methodology/Principal Findings To verify whether S. brasiliensis is associated with clinical manifestations of sporotrichosis, a cross-sectional study was performed in which Sporothrix isolates from 50 patients with different clinical manifestations were analyzed and their isolates were studied by phenotypic and genotypic methods. Data from these patients revealed a distinct clinical picture and therapeutic response in infections caused by Sporothrix brasiliensis (n = 45) compared to patients with S. schenckii sensu stricto (n = 5). S. brasiliensis was associated with disseminated cutaneous infection without underlying disease, hypersensitivity reactions, and mucosal infection, whereas patients with S. schenckii presented with less severe and more often localized disease, similar to the majority of previously described sporotrichosis cases. Interestingly, S. brasiliensis-infected patients overall required shorter durations of itraconazole (median 16 weeks) compared to the individuals with S. schenckii (median 24 weeks). Conclusions/Significance These findings suggest that Sporothrix species are linked to different clinical manifestations of sporotrichosis and that S. brasiliensis is effectively treated with oral itraconazole. PMID:25233227

  19. A homozygous mutation in the SCO2 gene causes a spinal muscular atrophy like presentation with stridor and respiratory insufficiency.

    Science.gov (United States)

    Pronicki, Maciej; Kowalski, Paweł; Piekutowska-Abramczuk, Dorota; Taybert, Joanna; Karkucinska-Wieckowska, Agnieszka; Szymanska-Debinska, Tamara; Karczmarewicz, Elzbieta; Pajdowska, Magdalena; Migdal, Marek; Milewska-Bobula, Bogumila; Sykut-Cegielska, Jolanta; Popowska, Ewa

    2010-05-01

    Infants with deficiency of cytochrome c oxidase (COX) due to SCO2 mutations observed so far usually demonstrated early cardiomyopathy, encephalopathy and lactic acidosis. Milder spinal muscular atrophy-like (SMA-like) phenotype was also rarely reported. The aim is to present 18 Polish patients with SCO2 mutations. Molecular study revealed p.E140K mutation in all cases (on 32 alleles); p.Q53X mutation and novel p.M177T change were identified in single patients. In three families no second mutation was found. Thirteen p.E140K homozygotes presented in infancy with floppiness and remarkable stridor. Survival motor neuron (SMN) gene deletion was excluded. Mild to moderate lactic academia was found. Neurological involvement manifested as spasticity and psychomotor retardation. In some patients strabismus, ptosis and episodes of seizures were seen. During second half of the year chronic respiratory failure with artificial respiration dependency appeared in all homozygotes. Heart involvement was never present at the beginning. Rapidly progressive hypertrophic cardiomyopathy developed in several patients at the terminal stage. The stridor was constant and striking feature. Skeletal muscle biopsy was performed in 16 patients including 11 homozygotes. Four pathological patterns were discerned - from neurogenic muscle changes, including spinal muscular atrophy (SMA) to unspecific findings. Histochemical cytochrome c oxidase (COX) deficit was not a constant feature. Significant decrease in respiratory chain complex IV activity was detected in muscle homogenate by spectrophotometric method only in 7 out of 12 examined cases. 1/Mutations of SCO2 gene should be considered as a possible cause of neurogenic skeletal muscle features (including SMA-like) in infants with encephalomyopathy even in the absence of heart involvement and COX deficit; 2/Inspiratory stridor may be symptomatic of SCO2 gene mutation(s). Copyright 2009 European Paediatric Neurology Society. Published by Elsevier

  20. A common FGFR3 gene mutation is present in achondroplasia but not in hypochondroplasia

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    Stoilov, I.; Kilpatrick, M.W.; Tsipouras, P. [Univ. of Connecticut Health Center, Farmington, CT (United States)

    1995-01-02

    Achondroplasia is the most common type of genetic dwarfism. It is characterized by disproportionate short stature and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. Recent studies mapped the achondroplasia gene on chromosome region 4p16.3 and identified a common mutation in the gene encoding the fibroblast growth factor receptor 3 (FGFR3). In an analysis of 19 achondroplasia families from a variety of ethnic backgrounds we confirmed the presence of the G380R mutation in 21 of 23 achondroplasia chromosomes studied. In contrast, the G380R mutation was not found in any of the 8 hypochondroplasia chromosomes studied. Futhermore, linkage studies in a 3-generation family with hypochondroplasia show discordant segregation with markers in the 4p16.3 region suggesting that at least some cases of hypochondroplasia are caused by mutations in a gene other than FGFR3. 27 refs., 2 figs.

  1. Alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models.

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    Kathryn Rozen-Gagnon

    2014-01-01

    Full Text Available Arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. To study the genetic mechanisms and determinants of these processes, we use chikungunya virus (CHIKV, a re-emerging human pathogen transmitted by the Aedes mosquito. We previously isolated a high fidelity (or antimutator polymerase variant, C483Y, which had decreased fitness in both mammalian and mosquito hosts, suggesting this residue may be a key molecular determinant. To further investigate effects of position 483 on RNA-dependent RNA-polymerase (RdRp fidelity, we substituted every amino acid at this position. We isolated novel mutators with decreased replication fidelity and higher mutation frequencies, allowing us to examine the fitness of error-prone arbovirus variants. Although CHIKV mutators displayed no major replication defects in mammalian cell culture, they had reduced specific infectivity and were attenuated in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and the variants exhibited significant defects in RNA synthesis. Consequently, these replication defects resulted in strong selection for reversion during infection of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV, which also reduced polymerase fidelity and generated replication defects in mosquito cells. However, replication defects were mosquito cell-specific and were not observed in Drosophila S2 cells, allowing us to evaluate the potential attenuation of mutators in insect models where pressure for reversion was absent. Indeed, the SINV mutator variant was attenuated in fruit flies. These findings confirm that residue 483 is a determinant regulating alphavirus polymerase fidelity and demonstrate proof of principle that arboviruses can be attenuated in mammalian and insect hosts by reducing fidelity.

  2. Clinical Heterogeneity in Patients With FOXP3 Mutations Presenting With Permanent Neonatal Diabetes

    Science.gov (United States)

    Rubio-Cabezas, Oscar; Minton, Jayne A.L.; Caswell, Richard; Shield, Julian P.; Deiss, Dorothee; Sumnik, Zdenek; Cayssials, Amely; Herr, Mathias; Loew, Anja; Lewis, Vaughan; Ellard, Sian; Hattersley, Andrew T.

    2009-01-01

    OBJECTIVE—Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by FOXP3 mutations. We aimed to determine the prevalence, genetics, and clinical phenotype of FOXP3 mutations in a large cohort with permanent neonatal diabetes (PNDM). RESEARCH DESIGN AND METHODS—The 11 coding exons and the polyadenylation region of FOXP3 were sequenced in 26 male subjects with diabetes diagnosed before 6 months of age in whom common genetic causes of PNDM had been excluded. Ten subjects had at least one additional immune-related disorder, and the remaining 16 had isolated diabetes. RESULTS—We identified four hemizygous FOXP3 mutations in 6 of 10 patients with associated immune-related disorders and in 0 of 16 patients with isolated diabetes (P = 0.002). Three patients with two novel mutations (R337Q and P339A) and the previously reported L76QfsX53 developed classic IPEX syndrome and died within the first 13 months. The novel mutation V408M was found in three patients from two unrelated families and had a mild phenotype with hypothyroidism and autoimmune enteropathy (n = 2) or nephrotic syndrome (n = 1) and survival to 12–15 years. CONCLUSIONS—FOXP3 mutations result in ∼4% of cases of male patients with permanent diabetes diagnosed before 6 months. Patients not only have classic IPEX syndrome but, unexpectedly, may have a more benign phenotype. FOXP3 sequencing should be performed in any male patient with the diagnosis of diabetes in the first 6 months who develops other possible autoimmune-associated conditions, even in the absence of full IPEX syndrome. PMID:18931102

  3. Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations.

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    Jason Q Core

    Full Text Available Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. As a test case, cultured skin-fibroblast nuclei of individuals possessing LMNA splice-site mutation (c.357-2A>G, LMNA nonsense mutation (c.736 C>T, pQ246X in exon 4, LMNA missense mutation (c.1003C>T, pR335W in exon 6, Hutchinson-Gilford Progeria Syndrome, and no LMNA mutations were analyzed. For each cell type, the percentage of dysmorphic nuclei, and other morphological features such as average nuclear area and average eccentricity were obtained. Compared to blind observers, our procedure implemented in Matlab codes possessed similar accuracy to manual counting of dysmorphic nuclei while being significantly more consistent. The automatic quantification of nuclear defects revealed a correlation between in vitro results and age of patients for initial symptom onset. Our results demonstrate the method's utility in experimental studies of diseases affecting nuclear shape through automated, unbiased, and accurate identification of dysmorphic nuclei.

  4. MYO5B Mutations in Patients With Microvillus Inclusion Disease Presenting With Transient Renal Fanconi Syndrome

    NARCIS (Netherlands)

    Golachowska, Magdalena R.; van Dael, Carin M. L.; Keuning, Hilda; Karrenbeld, Arend; Hoekstra, Dick; Gijsbers, Carolien F. M.; Benninga, Marc A.; Rings, Edmond H. H. M.; van Ijzendoorn, Sven C. D.

    2012-01-01

    Background and Objective: Microvillus inclusion disease (MVID) is a rare congenital enteropathy associated with brush border atrophy and reduced expression of enzymes at the enterocytes' apical surface. MVID is associated with mutations in the MYO5B gene, which is expressed in all epithelial

  5. Detection and Distribution of V1016Ikdr Mutation in the Voltage-Gated Sodium Channel Gene in Aedes aegypti (Diptera: Culicidae) Populations From Sergipe State, Northeast Brazil.

    Science.gov (United States)

    Dolabella, S S; Santos, R L C; Silva, M C N; Steffler, L M; Ribolla, P E M; Cavalcanti, S C H; Jain, S; Martins, A J

    2016-07-01

    Aedes aegypti (L.) resistance to pyrethroids was recorded in Brazil few years after its introduction as the adulticide in the National Dengue Control Program campaigns. Altered susceptibility to pyrethroids had been reported in the state of Sergipe, northeast Brazil, through biological assays, even before its use against Ae. aegypti in the state. Metabolic and target-site resistance mechanisms were also revealed in samples from Aracaju, the capital of Sergipe. Herein, we investigated the presence and distribution of the kdr mutation V1016Ikdr in Ae. aegypti populations from different municipalities of the state. Aedes aegypti eggs were collected from seven municipalities located in areas showing different climatic types and infestation levels. Approximately 20 Ae. aegypti females from each municipality (total of 135 subjects) were individually submitted to allele-specific polymerase chain reaction (AS-PCR) for the 1016 site of the voltage-gated sodium channel (NaV). The V1016Ikdr mutation was found in subjects from all the municipalities under study with a high frequency of heterozygotes in several locations. Homozygous recessive subjects (resistant kdr genotype) were found only in one municipality. The results suggest a wide distribution of the V1016Ikdr mutation in the northeast Brazil, which indicates urgent need for monitoring the effectiveness of the pyrethroids currently used for vector control. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. HIV-1 Drug Resistance Mutations Are Present in Six Percent of Persons Initiating Antiretroviral Therapy in Lusaka, Zambia

    NARCIS (Netherlands)

    Hamers, Raph L.; Siwale, Margaret; Wallis, Carole L.; Labib, Moheb; van Hasselt, Robbert; Stevens, Wendy S.; Schuurman, Rob; Wensing, Annemarie M. J.; van Vugt, Michèle; Rinke de Wit, Tobias F.

    2010-01-01

    Objective: To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008. Methods: Population sequencing of the HIV-1 pol gene was performed in the PharmAccess

  7. Sub-Saharan Africa descendents in Rio de Janeiro (Brazil): population and mutational data for 12 Y-STR loci.

    Science.gov (United States)

    Domingues, Patricia Mariana; Gusmão, Leonor; da Silva, Dayse Aparecida; Amorim, António; Pereira, Rinaldo W; de Carvalho, Elizeu F

    2007-05-01

    A male sample of 135 African descendents from the Rio de Janeiro population were typed for the 12 Y-chromosome short tandem repeat (STR) loci included in the PowerPlex Y System. A high haplotype diversity was observed (0.9971), with 91% of haplotypes being unique, demonstrating the usefulness and informative power of this Y-STR set in male lineage identification. Samples with shared haplotypes were additionally typed with the Yfiler kit, which includes five extra markers. The haplotype diversity when using the 17-Yfiler loci increased to (0.9998) with 97% unique haplotypes. The same set of Y-STRs was also typed in 135 father/son pairs and three single-step mutations were observed: one at DYS19 and two at DYS385. Genetic distance analysis showed highly significant differences in all pairwise comparisons between this sample of African descendents and the general population from Rio de Janeiro, as well as with Iberian and African samples from Portugal, Mozambique, Angola and Equatorial Guinea. Comparisons with samples from other regions in Brazil showed that heterogeneity does exist, indicating that a Y-haplotype database for the whole country should take into account the population sub-structure. Moreover, a strong European influence was detected, and thus, a Y-chromosome STR profile proves a rather poor indicator for the ethnic origin of an individual in Rio de Janeiro.

  8. Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2

    DEFF Research Database (Denmark)

    Meeths, Marie; Entesarian, Miriam; Al-Herz, Waleed

    2010-01-01

    in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH...... (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell...

  9. Mental healthcare in South America with a focus on Brazil: past, present, and future.

    Science.gov (United States)

    Loch, Alexandre Andrade; Gattaz, Wagner Farid; Rössler, Wulf

    2016-07-01

    South America and Brazil have undergone major reforms in their mental healthcare systems during the past few decades. The Caracas Declaration, formulated in Venezuela in 1990, states that mental healthcare should be directed toward community treatment rather than hospital-based models. We review how mental health services were previously organized and how they are currently provided to persons with mental illnesses. In many South American countries, the number of beds in psychiatric hospitals has been reduced (e.g., between 2001 and 2005, from 18.3 to 12.7 and from 38.7 to 25.6 per 100 000 persons in Chile and Brazil, respectively). Meanwhile, the number of psychiatric beds in general hospitals has increased slightly and more human resources are being devoted to mental health services. Nevertheless, the total number of beds is still insufficient and financing for mental health programs is far below the optimum. More than 20 years after the Caracas Declaration, much has been done but many changes are still required. Some reforms have already been proposed but not put into practice. Future efforts should include fighting against stigma and improving budgeting for mental healthcare, a lack of which might be interpreted as structural stigma.

  10. Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil.

    Science.gov (United States)

    Cota, Gláucia F; de Sousa, Marcos R; de Mendonça, Andrea Laender Pessoa; Patrocinio, Allan; Assunção, Luiza Siqueira; de Faria, Sidnei Rodrigues; Rabello, Ana

    2014-04-01

    Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality. To assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIV-infected patients diagnosed with VL during the same period as a comparator. The study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm3 received secondary prophylaxis with amphotericin B. Between 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients). HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group). The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode. Although VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with amphotericin B, HIV coinfection is related to a low clinical response

  11. Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil.

    Directory of Open Access Journals (Sweden)

    Gláucia F Cota

    2014-04-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality. OBJECTIVE: To assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIV-infected patients diagnosed with VL during the same period as a comparator. METHODS: The study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm3 received secondary prophylaxis with amphotericin B. RESULTS: Between 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients. HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group. The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode. CONCLUSION: Although VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with

  12. BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study.

    Science.gov (United States)

    Petrillo, Marco; Marchetti, Claudia; De Leo, Rossella; Musella, Angela; Capoluongo, Ettore; Paris, Ida; Benedetti Panici, Pierluigi; Scambia, Giovanni; Fagotti, Anna

    2017-09-01

    In the last decades, there have been several efforts to clarify the role of BRCA mutational status in women with advanced ovarian cancer, demonstrating its role in cancer development, as well as the prognostic significance of BRCA genotype. Our aim is to evaluate the correlation between BRCA mutational status and disease presentation in a large series of advanced high-grade serous ovarian cancer patients. This is a retrospective multicenter study including a consecutive series of newly diagnosed high-grade serous ovarian cancer patients with International Federation of Gynecology and Obstetrics stage IIIC-IV disease, at least 18 months of follow-up time, and tested for BRCA 1/2 germline mutation status. Disease presentation was analyzed using the following variables: laparoscopic predictive index value, incidence of bulky lymph nodes, and ovarian masses. Progression-free survival was defined as the months elapsed from initial diagnosis (staging laparoscopy) and recurrent disease or last follow-up. In all, 324 high-grade serous ovarian cancer patients received BRCA testing, and 273 fulfilled inclusion criteria. BRCA1/2 germline mutations were observed in 107 women (39.2%). No differences were documented according to BRCA mutation status in terms of International Federation of Gynecology and Obstetrics stage, CA125 levels, or presence of ascites. In patients with BRCA1/2 mutations we observed a higher incidence of peritoneal spread without ovarian mass (25.2% vs 13.9%; P value = .018) and of bulky lymph nodes (30.8% vs 17.5%; P value = .010) compared with women showing BRCA1/2 wild type genotype. Furthermore, women with BRCA1/2 mutations showed high peritoneal tumor load (laparoscopic predictive index value ≥8; 42.1% vs 27.1%; P value = .016) more frequently. Focusing on survival, no differences in term of median progression-free survival were observed among women treated with primary debulking surgery and neoadjuvant chemotherapy in the group of patients with

  13. The Point Mutation G461S in the MfCYP51 Gene is Associated with Tebuconazole Resistance in Monilinia fructicola Populations in Brazil.

    Science.gov (United States)

    Lichtemberg, Paulo S F; Luo, Yong; Morales, Rafael G; Muehlmann-Fischer, Juliana M; Michailides, Themis J; May De Mio, Louise L

    2017-12-01

    The ascomycete Monilinia fructicola is the causal agent of brown rot of stone fruit in Brazil, causing major pre- and postharvest losses. For many years, the demethylation inhibitor (DMI) fungicide tebuconazole has been used as the most effective active ingredient for controlling brown rot and, as a result, strains of M. fructicola resistant to this ingredient have emerged in many Brazilian states producing stone fruit. The aim of this study was to investigate the mechanisms associated with the resistance of M. fructicola to DMI tebuconazole. By sequencing the M. fructicola CYP51 (MfCYP51) gene, encoding the azole target sterol 14α-demethylase, a mutation was identified at the nucleotide position 1,492, causing the amino acid substitution from glycine to serine at the codon position 461, associated with reduced tebuconazole sensitivity. In addition, it was observed that MfCYP51 gene expression could play a secondary role in DMI fungicide resistance of M. fructicola strains in Brazil. However, for the specific isolate found to exhibit elevated expression levels of MfCYP51, no insertions that would trigger gene expression were found. Based on the point mutation associated with tebuconazole resistance, an allele-specific polymerase chain reaction method was developed to quickly identify resistant genotypes within the Brazilian population. This is the first report determining molecular mechanisms for DMI resistance identification for M. fructicola isolates from Brazil. This information provides an important advancement for risk assessment of DMI fungicides used to manage brown rot of stone fruit.

  14. Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil.

    Science.gov (United States)

    Fawkner-Corbett, David W; Khoo, Siew Kim; Duarte, Carminha M; Bezerra, Patricia G M; Bochkov, Yury A; Gern, James E; Le Souef, Peter N; McNamara, Paul S

    2016-01-01

    Human rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterize the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. Nasopharyngeal aspirates were collected from 630 children infected with RV-A and RV-C. However, in children with asthma/EVW, RV-C was detected relatively more frequently than RV-A (23% vs. 5%; P = 0.04). Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV-A and C species were detected. However, RV-C was more frequently found in children with asthma/EVW than RV-A. © 2015 Wiley Periodicals, Inc.

  15. Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil.

    Science.gov (United States)

    Seidinger, Ana Luiza; Mastellaro, Maria José; Paschoal Fortes, Fernanda; Godoy Assumpção, Juliana; Aparecida Cardinalli, Izilda; Aparecida Ganazza, Mônica; Correa Ribeiro, Raul; Brandalise, Silvia Regina; Dos Santos Aguiar, Simone; Yunes, José Andrés

    2011-05-15

    The inherited, low-penetrance arginine-to-histidine substitution at codon 337 (R337H) of the tumor protein 53 gene (TP53) is clustered in southeast Brazil (estimated frequency, 0.3%). Although its tumorigenic effect initially appeared to be tissue-specific, recent evidence suggests its association with a broader range of tumors. Therefore, the authors of this report investigated the spectrum of pediatric malignancies associated with the TP53 R337H mutation at a single referral institution in southeast Brazil. Genomic DNA samples from 493 children with malignancies were screened for the R337H mutation. Available tumor samples from carriers were investigated for loss of heterozygosity (LOH) and nuclear p53 accumulation. Clinical data were obtained from medical records. Sixty-five of 70 patients (93%) with adrenocortical tumors (ACTs), 9 of 13 patients (69%) with choroid plexus carcinoma (CPC), and 3 of 41 patients (7.3%) with osteosarcoma carried the mutation. The proportion of CPC to choroid plexus papilloma (CPP) was much higher than that reported elsewhere. Osteosarcoma in carriers had a significantly poorer outcome (P = .02). The mutation was not identified in patients who had acute lymphoblastic leukemia (ALL) (n = 187), recurrent ALL (n = 49), acute myeloid leukemia (n = 44), lymphoma (n = 30), non-CPC central nervous system tumors (n = 26), Ewing sarcoma (n = 25), or rhabdomyosarcoma (n = 8). Among the tumors that were available for analysis, LOH with retention of the mutant allele was confirmed in 21 of 21 ACTs, in 2 of 2 CPCs, and in 2 of 3 osteosarcomas that were positive for R337H. CPCs and osteosarcomas that were positive for R337H had marked nuclear accumulation of p53. The current findings demonstrated compellingly that the TP53 R337H mutation is associated not only with ACT but also with CPC and, to a lesser extent, with osteosarcoma, both of which are core-component tumors of the Li-Fraumeni syndrome. 2010 American Cancer Society.

  16. A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated With BRAF Mutations

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahmcke, Christina M.; Dahl, Christina

    2015-01-01

    , melanoma-related mortality, and all-cause mortality were examined. RESULTS: A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently......IMPORTANCE: Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly. OBJECTIVES: To determine the associations of clinicopathological tumor features......) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models. CONCLUSIONS AND RELEVANCE...

  17. Present international patterns of foreign direct investment: underlying causes and some policy implications for Brazil

    Directory of Open Access Journals (Sweden)

    François Chesnais

    2013-12-01

    Full Text Available An important feature of the 1980s has been the substantial fall in the flow of foreign direct investment (FDI to the developing countries and also, with the limited exception of the Asian NIE (Korea, Taiwan, Malaysia, Singapore and China, to the newly industrialized countries, in particular those in Latin America. FDI has been concentrated more than ever among the advanced industrialized countries of OECD. The same period has witnessed a number of extremely important changes, both in the nature and location of basic or key technologies, the role of technology in industrial competitiveness; the most appropriate industrial management paradigm following the difficulties of the "Fordist" one; the nature of predominant international supply or market structures; and the relationships between productive and financial capital. Today a number of governments in developing countries and in NIC, among them the new government of Brazil, are again engaged in an attempt to attract FDI and to make foreign capital one of the major pillars of industrial revival and future growth. This paper argues that this policy objective is both fairly illusory and largely mistaken. It is fairly illusory in that it seriously underestimates the nature and strength of the structural factors which have been at work since the mid-1970s and seriously modified the strategies and investment priorities of the TNC which under took the brunt of the investment in developing countries and NICs in the earlier "golden age" of the 1960s and 1970s . The objective of luring foreign capital again to Brazil in ways and on a level similar to the 1960s is also largely mistaken in that it fails to recognize that the change in technological paradigms has modified the parameters of international technology transfers (cf. Ernst and O'Connor, 1989 and made indigenous and endogenous industrial growth dependent to a much higher degree than in the previous period (19601975 on factors which foreign capital

  18. Clinical presentation of congenital sialidosis in a patient with a neuraminidase gene frameshift mutation.

    Science.gov (United States)

    Buchholz, T; Molitor, G; Lukong, K E; Praun, M; Genzel-Boroviczény, O; Freund, M; Pshezhetsky, A V; Schulze, A

    2001-01-01

    Congenital sialidosis is a rare lysosomal storage disease caused by a primary neuraminidase deficiency which results from defects in the neuraminidase gene on chromosome 6p. The inheritance is autosomal recessive. Patients exhibit excessive urinary excretion of bound sialic acid and decreased or undetectable amounts of neuraminidase activity in various tissues. The clinical expression is variable, but ascites and hepatosplenomegaly are hallmarks of the disease. Skeletal abnormalities, facial dysmorphism and inguinal herniae have been described in most of the few reported cases. We describe a baby girl with biochemically proven sialidosis, who in addition to the above clinical features, had severely dilated coronary arteries, excessive retinal vascular tortuosity and an erythematous, macular rash. Homozygosity for a frameshift mutation at residue 623 of the neuraminidase cDNA was found. We speculate that the additional features found in our patient might be associated with the here described genotype of congenital sialidosis. Severely dilated coronary arteries, excessive retinal vascular tortuosity and an erythematous macular rash might be associated features of congenital sialidosis.

  19. Telemental health in Brazil: past, present and integration into primary care

    Directory of Open Access Journals (Sweden)

    Rodrigo Da Silva Dias

    2015-04-01

    Full Text Available Background Telemental Health Care has reported very good results and is included within mental health priorities by the World Health Organization. Objective To provide an overview of the current situation of the integration of Brazilian telemedicine activities into primary health care. Methods Critical review based on MEDLINE database, using the keywords “telemedicine”, “primary health care” “mental health” and “telemental health”, on websites of the Brazilian Ministry of Health and Brazilian Telehealth Network Program, and on personal communication. Results The Brazilian Telehealth Network Program is well positioned and connects primary health care with academic centers. Regulations standards allow a broader scope of activities for psychologists, however, are more restrictive for physicians. In Brazil most of telemental health activities are focused on education and second opinion consulting. A huge challenge must be overcome considering the regional differences and the telehealth implementation experience. Research initiatives have been initiated both in the implementation and evaluation of the mental health assistance into primary health care. Discussion Brazilian Telemental Health initiatives into Primary Care are aligned with other examples around the world, have a great potential for improving mental health care service delivery, and access to proper mental health care, especially if articulated in a national program and coordinated research.

  20. Linalool and methyl chavicol present basil (Ocimum sp. cultivated in Brazil Linalol e metil-chavicol presentes em manjericão (Ocimum sp. cultivados no Brasil

    Directory of Open Access Journals (Sweden)

    R.A. de Oliveira

    2013-01-01

    Full Text Available In Brazil, Ocimum species are commonly known as aromatic and restorative herbs. The present research aimed to study the chemical composition of the essential oils of fresh and dry basil (Ocimum sp leaves obtained by hydrodistillation and analyzed by GC-FID and GC-MS. The obtained yield was 0.70% for dry leaves and 0.26% for fresh leaves. The major compounds were: linalool (29.50-32.26% and methyl chavicol (36.81-41.62%. Eucalyptol could also be detected (9.99-7.68%. The oil from dry leaves presented a more complex chemical composition. This study serves to contribute to the knowledge of medicinal plants occurring in Brazil.No Brasil, as espécies de Ocimum são conhecidas como ervas aromáticas e restaurativas. Nesse trabalho foi estudado a composição química dos óleos essenciais das folhas frescas e secas de manjericão (Ocimum sp obtido por hidrodestilação e analisados por CG-FID e CG-EM. Os teores encontrados foram de 0,70% para as folhas secas e 0,26% para as folhas frescas. Os componentes majoritários foram: Linalol (29,50-32,26% e metil-chavicol (36,81-41,62%. Eucaliptol também foi detectado (9,99-7,68%. O óleo das folhas secas apresentou composição química mais complexa. Esse trabalho contribui para o conhecimento das plantas medicinais de ocorrência no Brasil.

  1. The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia.

    Science.gov (United States)

    Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia

    2015-04-01

    Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

  2. The epidermal growth factor receptor (EGFR / HER-1 gatekeeper mutation T790M is present in European patients with early breast cancer.

    Directory of Open Access Journals (Sweden)

    Vahid Bemanian

    Full Text Available The epidermal growth factor receptor (EGFR is one of the major oncogenes identified in a variety of human malignancies including breast cancer (BC. EGFR-mutations have been studied in lung cancer for some years and are established as important markers in guiding therapy with tyrosine kinase inhibitors (TKIs. In contrast, EGFR-mutations have been reported to be rare if not absent in human BC, although recent evidence has suggested a significant worldwide variation in somatic EGFR-mutations. Therefore, we investigated the presence of EGFR-mutations in 131 norwegian patients diagnosed with early breast cancer using real-time PCR methods. In the present study we identified three patients with an EGFR-T790M-mutation. The PCR-findings were confirmed by direct Sanger sequencing. Two patients had triple-negative BC (TNBC while the third was classified as luminal-A subtype. The difference in incidence of T790M mutations comparing the TNBC subgroup with the other BC subgroups was statistical significant (P = 0.023. No other EGFR mutations were identified in the entire cohort. Interestingly, none of the patients had received any previous cancer treatment. To our best knowledge, the EGFR-T790M-TKI-resistance mutation has not been previously detected in breast cancer patients. Our findings contrast with the observations made in lung cancer patients where the EGFR-T790M-mutation is classified as a typical "second mutation"causing resistance to TKI-therapy during ongoing anticancer therapy. In conclusion, we have demonstrated for the first time that the EGFR-T790M-mutation occurs in primary human breast cancer patients. In the present study the EGFR-T790M mutation was not accompanied by any simultaneous EGFR-activating mutation.

  3. The epidermal growth factor receptor (EGFR / HER-1) gatekeeper mutation T790M is present in European patients with early breast cancer.

    Science.gov (United States)

    Bemanian, Vahid; Sauer, Torill; Touma, Joel; Lindstedt, Bjørn Arne; Chen, Ying; Ødegård, Hilde Presterud; Vetvik, Katja Marjaana; Bukholm, Ida Rashida; Geisler, Jürgen

    2015-01-01

    The epidermal growth factor receptor (EGFR) is one of the major oncogenes identified in a variety of human malignancies including breast cancer (BC). EGFR-mutations have been studied in lung cancer for some years and are established as important markers in guiding therapy with tyrosine kinase inhibitors (TKIs). In contrast, EGFR-mutations have been reported to be rare if not absent in human BC, although recent evidence has suggested a significant worldwide variation in somatic EGFR-mutations. Therefore, we investigated the presence of EGFR-mutations in 131 norwegian patients diagnosed with early breast cancer using real-time PCR methods. In the present study we identified three patients with an EGFR-T790M-mutation. The PCR-findings were confirmed by direct Sanger sequencing. Two patients had triple-negative BC (TNBC) while the third was classified as luminal-A subtype. The difference in incidence of T790M mutations comparing the TNBC subgroup with the other BC subgroups was statistical significant (P = 0.023). No other EGFR mutations were identified in the entire cohort. Interestingly, none of the patients had received any previous cancer treatment. To our best knowledge, the EGFR-T790M-TKI-resistance mutation has not been previously detected in breast cancer patients. Our findings contrast with the observations made in lung cancer patients where the EGFR-T790M-mutation is classified as a typical "second mutation"causing resistance to TKI-therapy during ongoing anticancer therapy. In conclusion, we have demonstrated for the first time that the EGFR-T790M-mutation occurs in primary human breast cancer patients. In the present study the EGFR-T790M mutation was not accompanied by any simultaneous EGFR-activating mutation.

  4. Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation.

    NARCIS (Netherlands)

    Zankl, A.; Elakis, G.; Susman, R.D.; Inglis, G.; Gardener, G.; Buckley, M.F.; Roscioli, T.

    2008-01-01

    We present prenatal and postnatal features of a patient with severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). Mutation analysis confirmed the clinical diagnosis by detecting the FGFR3 Lys650Met mutation. This case, one of only six with molecular analysis reported in

  5. Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease.

    Science.gov (United States)

    Bonafé, Luisa; Kariminejad, Ariana; Li, Jia; Royer-Bertrand, Beryl; Garcia, Virginie; Mahdavi, Shokouholsadat; Bozorgmehr, Bita; Lachman, Ralph L; Mittaz-Crettol, Lauréane; Campos-Xavier, Belinda; Nampoothiri, Sheela; Unger, Sheila; Rivolta, Carlo; Levade, Thierry; Superti-Furga, Andrea

    2016-09-01

    To establish a diagnosis and provide counseling and treatment for 3 adult patients from one family presenting with peripheral osteolysis. Following clinical and radiographic assessment, exome sequencing, targeted gene resequencing, and determination of enzyme activity in cultured fibroblasts were performed. The proband (age 40 years) had a history of episodic fever and pain in childhood that subsided around puberty. He and 2 of his older sisters (ages 58 and 60 years, respectively) showed adult-onset progressive shortening of fingers and toes with redundancy of the overlying skin. Radiographs showed severe osteolysis of the distal radius and ulna, carpal bones, metacarpal bones, and phalanges. Sequencing of the known genes for recessively inherited osteolysis, MMP2 and MMP14, failed to show pathogenic mutations. Exome sequencing revealed compound heterozygosity for mutations c.505T>C (p.Trp169Arg) and c.760A>G (p.Arg254Gly) in ASAH1, the gene coding for acid ceramidase. Sanger sequencing confirmed correct segregation in the family, and enzyme activity in fibroblast cultures from the patients was reduced to ∼8% of that in controls, confirming a diagnosis of Farber's disease. Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long-term skeletal manifestations of acid ceramidase deficiency (Farber's disease) in what appear to be the oldest affected individuals known so far. © 2016, American College of Rheumatology.

  6. Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Beatriz Piva e Mattos

    Full Text Available Abstract Background: Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM. However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country. Objective: To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations. Methods: Direct DNA sequencing of all encoding regions of three sarcomeric genes was conducted in 43 consecutive individuals of ten unrelated families. Results: Mutations for CMH have been found in 25 (58% patients of seven (70% of the ten study families. Fourteen (56% individuals were phenotype-positive. All mutations were missense, four (66% in MYH7 and two (33% in MYBPC3. We have not found mutations in the TNNT2 gene. Mutations in MYH7 were identified in 20 (47% patients of six (60% families. Two of them had not been previously described. Mutations in MYBPC3 were found in seven (16% members of two (20% families. Two (5% patients showed double heterozygosis for both genes. The mutations affected different domains of encoded proteins and led to variable phenotypic expression. A family history of HCM was identified in all genotype-positive individuals. Conclusions: In this first genetic-molecular analysis carried out in the south of Brazil, we found mutations in the sarcomeric genes MYH7 and MYBPC3 in 58% of individuals. MYH7-related disease was identified in the majority of cases with mutation.

  7. Clinical presentation of early-onset Alzheimer's disease as a result of mutation in exon 12 of the PSEN-1 gene.

    Science.gov (United States)

    Klimkowicz-Mrowiec, Aleksandra; Bodzioch, M; Szczudlik, A; Slowik, A

    2014-12-01

    Mutations in the gene for presenilin 1 (PSEN-1) cause familial, early-onset Alzheimer's disease (EOAD). Diagnosis of EOAD is often a challenge because of the high frequency of atypical presentations. Clinical manifestation of EOAD may vary depending on underlying mutation; specific genetic mutations influence development of specific clinical phenotypes; however, intrafamilial phenotypic heterogeneity has also been noted in some pedigrees. We report a case of a 36-year-old woman presenting with progressive behavioral disturbances, dementia, involuntary movements, pyramidal signs, epilepsy, and a family history of early-onset dementia accompanied by involuntary movements. On genetic testing, the mutation at codon 424 (Leu→Arg) in PSEN-1 gene was identified. Our case describes a new phenotype of a known mutation of PSEN-1 at codon 424. © The Author(s) 2014.

  8. Presentation: Iron ore interpretation using gravity-gradient inversions in the Carajás, Brazil

    OpenAIRE

    Carlos, Dionisio Uendro; Uieda, Leonardo; Li, Yaoguo; Barbosa, Valeria C. F.; Braga, Marco Antonio; Angeli, Glauco; Peres, Guilherme Gravina

    2013-01-01

    Slides for the oral presentation given by Leonardo Uieda (on behalf of Dionisio Uendro Carlos) at the 2012 SEG International Exposition and Eighty-Second Annual Meeting, Las Vegas, USA. Download the pdf of the expanded abstract from the links bellow.

  9. Digital Mobile Planetarium: Lifting astronomical concepts presented by teachers in the city of Caraguatatuba, Brazil

    Science.gov (United States)

    Voelzke, Marcos Rincon; Pereira Gonzaga, Edson

    2015-08-01

    In this work, a survey of alternative conceptions about basic concepts of Astronomy was carried out on the North Coast of São Paulo with 478 people, visitors of the Digital Mobile Planetarium (DMP). Rodolfo Langhi’s thought about alternative conceptions (2005), considered very important, was the base for this study, choosen because it allows to identify these concepts before the intervention methodology, which renders possible to prepare contextualized presentations and helps to propose to teachers - and consequently to students - to compare what they already know with the new information obtained in the sessions at the DMP of the University Cruzeiro do Sul. This is a case study with a quantitative survey and a qualitative analysis of data on astronomical concepts collected through a questionnaire.

  10. Arachnids of medical importance in Brazil: main active compounds present in scorpion and spider venoms and tick saliva.

    Science.gov (United States)

    Cordeiro, Francielle A; Amorim, Fernanda G; Anjolette, Fernando A P; Arantes, Eliane C

    2015-01-01

    Arachnida is the largest class among the arthropods, constituting over 60,000 described species (spiders, mites, ticks, scorpions, palpigrades, pseudoscorpions, solpugids and harvestmen). Many accidents are caused by arachnids, especially spiders and scorpions, while some diseases can be transmitted by mites and ticks. These animals are widely dispersed in urban centers due to the large availability of shelter and food, increasing the incidence of accidents. Several protein and non-protein compounds present in the venom and saliva of these animals are responsible for symptoms observed in envenoming, exhibiting neurotoxic, dermonecrotic and hemorrhagic activities. The phylogenomic analysis from the complementary DNA of single-copy nuclear protein-coding genes shows that these animals share some common protein families known as neurotoxins, defensins, hyaluronidase, antimicrobial peptides, phospholipases and proteinases. This indicates that the venoms from these animals may present components with functional and structural similarities. Therefore, we described in this review the main components present in spider and scorpion venom as well as in tick saliva, since they have similar components. These three arachnids are responsible for many accidents of medical relevance in Brazil. Additionally, this study shows potential biotechnological applications of some components with important biological activities, which may motivate the conducting of further research studies on their action mechanisms.

  11. R248G cystic fibrosis transmembrane conductance regulator mutation in three siblings presenting with recurrent acute pancreatitis and reproductive issues: a case series.

    Science.gov (United States)

    Villalona, Seiichi; Glover-López, Guillermo; Ortega-García, Juan Antonio; Moya-Quiles, Rosa; Mondejar-López, Pedro; Martínez-Romero, Maria C; Rigabert-Montiel, Mariano; Pastor-Vivero, María D; Sánchez-Solís, Manuel

    2017-02-15

    Mutational combinations of the cystic fibrosis transmembrane conductance regulator, CFTR, gene have different phenotypic manifestations at the molecular level with varying clinical consequences for individuals possessing such mutations. Reporting cystic fibrosis transmembrane conductance regulator mutations is important in understanding the genotype-phenotype correlations and associated clinical presentations in patients with cystic fibrosis. Understanding the effects of mutations is critical in developing appropriate treatments for individuals affected with cystic fibrosis, non-classic cystic fibrosis, or cystic fibrosis transmembrane conductance regulator-related disorders. This is the first report of related individuals possessing the R248G missense cystic fibrosis transmembrane conductance regulator mutation and we present their associated clinical histories. All three patients are of Spanish descent. Deoxyribonucleic acid analysis revealed that all three siblings possessed a novel c.742A>G mutation, resulting in a p.Arg248Gly (R248G) amino acid change in exon 6 in trans with the known N1303K mutant allele. Case 1 patient is a 39-year-old infertile man presenting with congenital unilateral absence of the vas deferens and recurrent episodes of epigastric pain. Case 2 patient is a 32-year-old woman presenting with periods of infertility, two previous spontaneous abortions, recurrent epigastric pain, and recurrent pancreatitis. Case 3 patient is a 29-year-old woman presenting with recurrent pancreatitis and epigastric pain. We report the genotype-phenotype correlations and clinical manifestations of a novel R248G cystic fibrosis transmembrane conductance regulator mutation: congenital unilateral absence of the vas deferens in males, reduced female fertility, and recurrent acute pancreatitis. In addition, we discuss the possible functional consequences of the mutations at the molecular level.

  12. Female heterozygotes for the hypomorphic R40H mutation can have ornithine transcarbamylase deficiency and present in early adolescence: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Kirk Edwin P

    2010-11-01

    Full Text Available Abstract Introduction Ornithine transcarbamylase deficiency is the most common hereditary urea cycle defect. It is inherited in an X-linked manner and classically presents in neonates with encephalopathy and hyperammonemia in males. Females and males with hypomorphic mutations present later, sometimes in adulthood, with episodes that are frequently fatal. Case presentation A 13-year-old Caucasian girl presented with progressive encephalopathy, hyperammonemic coma and lactic acidosis. She had a history of intermittent regular episodes of nausea and vomiting from seven years of age, previously diagnosed as abdominal migraines. At presentation she was hyperammonemic (ammonia 477 μmol/L with no other biochemical indicators of hepatic dysfunction or damage and had grossly elevated urinary orotate (orotate/creatinine ratio 1.866 μmol/mmol creatinine, reference range A mutation was identified in the ornithine transcarbamylase gene (OTC in our patient confirming the first symptomatic female shown heterozygous for the R40H mutation. A review of the literature and correspondence with authors of patients with the R40H mutation identified one other symptomatic female patient who died of hyperammonemic coma in her late teens. Conclusions This report expands the clinical spectrum of presentation of ornithine transcarbamylase deficiency to female heterozygotes for the hypomorphic R40H OTC mutation. Although this mutation is usually associated with a mild phenotype, females with this mutation can present with acute decompensation, which can be fatal. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of unexplained acute confusion, even without a suggestive family history.

  13. Ki-ras gene mutations are invariably present in low-grade mucinous tumors of the vermiform appendix.

    Science.gov (United States)

    Zauber, Peter; Berman, Errol; Marotta, Stephen; Sabbath-Solitare, Marlene; Bishop, Timothy

    2011-07-01

    Low-grade mucinous tumors of the appendix appear to have a simple histological structure. Paradoxically, reports have suggested a greater frequency of Ki-ras gene mutation in these lesions than in more complex lesions such as benign colonic adenomas and carcinomas. We assessed several molecular genetic changes, including Ki-ras gene mutations, in a large series of low-grade mucinous tumors of the appendix. We retrospectively ascertained low-grade mucinous tumors of the appendix from computerized pathology records. Extracted DNA was analyzed for APC and DCC gene loss of heterozygosity, microsatellite instability and for the presence of Ki-ras gene mutation using standard molecular techniques. Controls consisted of normal appendices, other appendiceal neoplasms, and ovarian mucinous cystadenomas. A total of 31 low-grade appendiceal mucinous tumors were identified. All were microsatellite stable and none demonstrated loss of heterozygosity for the APC or DCC genes. By contrast, all 31 lesions contained a Ki-ras gene mutation. The presence of a Ki-ras gene mutation in all lesions, with no other molecular changes identified, strongly suggests a possible etiological role of the Ki-ras mutation in the development of this particular lesion of the appendix. Based on other work regarding intestinal bacteria, we hypothesize a relationship between chronic inflammation of the appendix from bacterial overgrowth and Ki-ras gene mutation.

  14. Compostos bioativos presentes em amora-preta (Rubus spp. Bioactive compounds of blackberry fruits (Rubus spp. grown in Brazil

    Directory of Open Access Journals (Sweden)

    Daniela Souza Ferreira

    2010-09-01

    and, or, inhibitors of degenerative disorders; however, data regarding the bioactive compounds in blackberry cultivated in Brazil are rare. Thus, the objectives of the present study were to identify the anthocyanins and carotenoids in blackberry (Rubus spp., to determine the total contents of phenolic compounds, flavonoids, carotenoids, and total, monomeric, polimeric and co-pigmented anthocyanins, and the antioxidant capacity against the free radicals ABTS and DPPH. The total carotenoids level was low (86.5 ± 0.2 µg/100 g, with all-trans-β-carotene (39.6 % and all-trans-lutein (28.2 % as the major ones. The blackberries showed high antioxidant status mainly due to the high level of monomeric anthocyanins (104.1 ± 1.8 mg/100 g de fruta, presence of polimeric anthocyanins (22.9 ± 0.4 %, low percentage of co-pigmented anthocyanins (1.6 ± 0.1 % and high contents of phenolic compounds (241.7 ± 0.8 mg gallic acid equivalent/100 g and total flavonoids (173.7 ± 0.7 mg catechin equivalent/100 g. Cyanidin 3-glucoside was the major anthocyanin (92.9 %. These results indicate that the blackberry cultivated in Brazil can be considered a rich natural source of antioxidants and pigments.

  15. Pseudohypoparathyroidism type Ia: a novel GNAS mutation in a Brazilian boy presenting with an early primary hypothyroidism.

    Science.gov (United States)

    Alves, Cresio; Sampaio, Silvana; Barbieri, Anna Maria; Mantovani, Giovanna

    2013-01-01

    Pseudohypoparathyroidism type Ia (PHP Ia) is a rare disease characterized by an elevated parathyroid hormone due to the resistance to its action in target tissues. We report a new GNAS mutation causing PHP Ia and an atypical early-onset primary hypothyroidism. A 3-year-old boy was diagnosed with obesity, delayed pyschomotor development, and round face. The laboratory evaluation at the age of 1 year showed primary hypothyroidism, hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase, and parathyroid hormone. These data led to the diagnosis of PHP Ia. Molecular analysis revealed a novel missense mutation in GNAS exon 1 (TCG→CGC, Cys3→Arg) in both the child and his mother. Although previously reported cases described delayed subclinical hypothyroidism as the more common thyroid abnormality, we report a not previously described GNAS mutation associated with an atypical early-onset primary hypothyroidism. These observations broaden the clinical spectrum of PHP Ia and its associated mutations.

  16. Presentation

    Directory of Open Access Journals (Sweden)

    Eduardo Vicente

    2013-06-01

    Full Text Available In the present edition of Significação – Scientific Journal for Audiovisual Culture and in the others to follow something new is brought: the presence of thematic dossiers which are to be organized by invited scholars. The appointed subject for the very first one of them was Radio and the invited scholar, Eduardo Vicente, professor at the Graduate Course in Audiovisual and at the Postgraduate Program in Audiovisual Media and Processes of the School of Communication and Arts of the University of São Paulo (ECA-USP. Entitled Radio Beyond Borders the dossier gathers six articles and the intention of reuniting works on the perspectives of usage of such media as much as on the new possibilities of aesthetical experimenting being build up for it, especially considering the new digital technologies and technological convergences. It also intends to present works with original theoretical approach and original reflections able to reset the way we look at what is today already a centennial media. Having broadened the meaning of “beyond borders”, four foreign authors were invited to join the dossier. This is the first time they are being published in this country and so, in all cases, the articles where either written or translated into Portuguese.The dossier begins with “Radio is dead…Long live to the sound”, which is the transcription of a thought provoking lecture given by Armand Balsebre (Autonomous University of Barcelona – one of the most influential authors in the world on the Radio study field. It addresses the challenges such media is to face so that it can become “a new sound media, in the context of a new soundscape or sound-sphere, for the new listeners”. Andrew Dubber (Birmingham City University regarding the challenges posed by a Digital Era argues for a theoretical approach in radio studies which can consider a Media Ecology. The author understands the form and discourse of radio as a negotiation of affordances and

  17. A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences

    Directory of Open Access Journals (Sweden)

    Yat-Fung Shea

    2016-02-01

    Full Text Available There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1 mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p < 0.001 and were more commonly affected by seizures, spastic paraparesis, myoclonus, and cerebellar signs (p < 0.001, p < 0.001, p = 0.003, and p = 0.002, respectively. Patients with PSEN2 mutations have a delayed AOO with longest disease duration and presented more frequently with disorientation (p = 0.03. Patients with amyloid precursor protein (APP mutations presented more frequently with aggression (p = 0.02 and those with APP duplication presented more frequently with apraxia (p = 0.03. PSEN1 mutations before codon 200 had an earlier AOO than those having mutations after codon 200 (41.4 ± 8.0 years vs. 44.7 ± 8.7 years, p < 0.001. Because 42.9% of the mutations reported are novel, the mutation spectrum and clinical features in Asian FAD families could be different from that of whites. Asian patients with PSEN1 mutations presented more frequently with disorientation (p = 0.02 and personality change (p = 0.01 but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02. Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites.

  18. CLINICAL PRESENTATION AND DISEASE COURSE OF USHER SYNDROME BECAUSE OF MUTATIONS IN MYO7A OR USH2A.

    Science.gov (United States)

    Testa, Francesco; Melillo, Paolo; Bonnet, Crystel; Marcelli, Vincenzo; de Benedictis, Antonella; Colucci, Raffaella; Gallo, Beatrice; Kurtenbach, Anne; Rossi, Settimio; Marciano, Elio; Auricchio, Alberto; Petit, Christine; Zrenner, Eberhart; Simonelli, Francesca

    2017-08-01

    To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively. Eighty-eight patients with a clinical diagnosis of USH1 (26 patients) or USH2 (62 patients) were retrospectively evaluated. Of these, 48 patients had 2 disease-causing mutations in MYO7A (10 USH1 patients), USH2A (33 USH2 patients), and other USH (5 patients) genes. Clinical investigation included best-corrected visual acuity, Goldmann visual field, fundus photography, electroretinography, and audiologic and vestibular assessments. Longitudinal analysis was performed over a median follow-up time of 3.5 years. Patients carrying mutations in MYO7A had a younger age of onset of hearing and visual impairments than those carrying mutations in USH2A, leading to an earlier diagnosis of the disease in the former patients. Longitudinal analysis showed that visual acuity and visual field decreased more rapidly in subjects carrying MYO7A mutations than in those carrying USH2A mutations (mean annual exponential rates of decline of 3.92 vs. 3.44% and of 8.52 vs. 4.97%, respectively), and the former patients reached legal blindness on average 15 years earlier than the latter. The current study confirmed a more severe progression of the retinal disease in USH1 patients rather than in USH2 patients. Furthermore, most visual symptoms (i.e., night blindness, visual acuity worsening) occurred at an earlier age in USH1 patients carrying mutations in MYO7A.

  19. A novel mutation in ABCA1 gene causing Tangier Disease in an Italian family with uncommon neurological presentation

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    Marco Ceccanti

    2016-11-01

    Full Text Available Tangier disease is an autosomal recessive disorder characterized by severe reduction in HDL-cholesterol and peripheral lipid storage. We describe a family with c.5094C>A p.Tyr16980* mutation in the ABCA1 gene, clinically characterized by syringomyelic-like anesthesia, demyelinating multineuropathy and reduction in intraepidermal small fibers innervation. In the proband patient, cardiac involvement determined a myocardial infarction; lipid storage was demonstrated in gut, cornea and aortic wall. The reported ABCA1 mutation has never been described before in a Tangier family.

  20. Presentation of hemophagocytic lymphohistiocytosis due to a novel MUNC 13–4 mutation masked by partial therapeutic immunosuppression

    Directory of Open Access Journals (Sweden)

    Garrett Jackie P-D

    2012-05-01

    Full Text Available Abstract Hemophagocytic lymphohistiocytosis is a potentially fatal disease characterized by excessive macrophage and lymphocyte activity. Patients can be affected following immune activation after an oncologic, autoimmune or infectious trigger. An associated gene mutation may be found which impairs cytolytic lymphocyte function. We describe a pediatric case of hemophagocytic lymphohistiocytosis with a novel mutation of MUNC 13–4 whose diagnosis was confounded by concurrent immunosuppression. Clinical reassessment for hemophagocytic lymphohistiocytosis is necessary in persistently febrile patients with laboratory derangements in the setting of immunosuppressive agent exposure.

  1. ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal recessive cutis laxa syndrome type IIA

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    D. Bahena-Bahena

    2014-01-01

    Full Text Available Patients with ARCL-IIA harbor mutations in ATP6V0A2 that codes for an organelle proton pump. The ARCL-IIA syndrome characteristically presents a combined glycosylation defect affecting N-linked and O-linked glycosylations, differentiating it from other cutis laxa syndromes and classifying it as a Congenital Disorder of Glycosylation (ATP6V0A2-CDG. We studied two Mexican Mestizo patients with a clinical phenotype corresponding to an ARCL-IIA syndrome. Both patients presented abnormal transferrin (N-linked glycosylation but Patient 1 had a normal ApoCIII (O-linked glycosylation profile. Mutational screening of ATP6V0A2 using cDNA and genomic DNA revealed in Patient 1 a previously reported homozygous nonsense mutation c.187C>T (p.R63X associated with a novel clinical finding of a VSD. In Patient 2 we found a homozygous c.2293C>T (p.Q765X mutation that had been previously reported but found that it also altered RNA processing generating a novel transcript not previously identified (r.2176_2293del; p.F726Sfs*10. This is the first report to describe Mestizo patients with molecular diagnosis of ARCL-IIA/ATP6V0A2-CDG and to establish that their mutations are the first to be found in patients from different regions of the world and with different genetic backgrounds.

  2. Distribution of the PKU mutation 165T in Spain and Latin America

    Energy Technology Data Exchange (ETDEWEB)

    Perez, B.; deLucca, M.; Desviat, L.R. [UAM-CSIC, Madrid (Spain)] [and others

    1994-09-01

    The 165T mutation is the second most common mutation in the Spanish PKU patients. In order to provide some additional data about the origin of this mutation, we have analyzed 452 PKU alleles from all regions of Spain. The mutation was found in 9% of alleles. We have found a South-North gradient with a highest frequency in the South and the lowest in the North. In the North-West regions (which has the greatest Celtic influence in Spain) the frequency was 7%. The chromosomes bearing this mutation contained the 8 repeat VNTR allele, as has been described in other populations. In view of these results, we suggest an origin other than Celtic for this mutation. On the other hand, we have analyzed 406 PKU alleles from five Latin American countries, 158 from Brazil, 170 from Chile, 56 from Argentina, 14 from Mexico and 8 from Venezuela. Unlike the results of the IVS10 mutation, 165T is present in Latin America with a low frequency. The results show that this mutation is rare in Chile (1%) and is absent in the chromosomes analyzed from Argentina, Mexico and Venezuela. Only in Brazil has this mutation been found in 5% of the alleles. Up to now, Spain is the only Mediterranean country where this mutation is present with a relatively high frequency. This mutation has been detected in the Portuguese patients and would also have migrated to Brazil.

  3. Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5)

    DEFF Research Database (Denmark)

    Pagel, Julia; Beutel, Karin; Lehmberg, Kai

    2012-01-01

    changes detectable in this cohort. Patients with exon 15 splice-site mutations (n = 13) developed clinical manifestations significantly later than patients with other mutations (median age, 4.1 year vs 2 months) and showed less severe impairment of degranulation and cytotoxic function of NK cells and CTLs....... Patients with FHL5 showed several atypical features, including sensorineural hearing deficit, abnormal bleeding, and, most frequently, severe diarrhea that was only present in early-onset disease. In conclusion, we report the largest cohort of patients with FHL5 so far, describe an extended disease...

  4. Differing clinical presentations of two unrelated cases of X-linked adrenoleukodystrophy with identical mutation Y296C in the ABCD1 gene.

    Science.gov (United States)

    Sutovský, Stanislav; Kolníková, Miriam; Petrovic, Róbert; Kollár, Branislav; Siarnik, Pavel; Chandoga, Ján; Fischerová, Mária; Turcáni, Peter

    2014-01-01

    X-linked adrenoleukodystrophy is a genetically determined disorder that causes varying degrees of malfunction of the adrenal cortex and central nervous system. Our aim was to investigate the occurrence of known, or new, mutations in the ABCD1 gene in two unrelated patients with clinical suspicion of the adrenoleukodystrophy. Two unrelated patients - the first with behavioral changes, the second with progressive cognitive deficit - underwent a clinical and genetic examination in order to establish a diagnosis and discover a possible mutation. In the first patient, a 47 year old man, the clinical examination showed dementia of the frontal type and spastic quadriparesis. The patient also suffered from adrenal insufficiency for 6 years. An MRI showed confluent hyperintensive lesions in FLAIR images in the frontal lobe of both hemispheres. The second patient, a 16 year old boy, suffered also from Addison's disease since the age of 9, and developed cognitive deficit in the course of one year. The MRI showed posterior atrophy and hyperintensive lesions in parietal and occipital lobes in T2WI. In both cases, genetic analyses showed a missense mutation at the codon 887 (A>G) in exon 1 of the ABCD1 gene, predicting the substitution Y296C in the ALD protein. We detected the same mutation of the ABCD1 gene in two unrelated patients with ALD. In the first case there was frontal lobe involvement, in the second case parieto-occipital involvement. Both pathologic involvement and clinical presentation differed in two cases of the same mutation.

  5. Screening for germline BRCA1, BRCA2, TP53 and CHEK2 mutations in families at-risk for hereditary breast cancer identified in a population-based study from Southern Brazil

    Directory of Open Access Journals (Sweden)

    Edenir Inêz Palmero

    2016-01-01

    Full Text Available Abstract In Brazil, breast cancer is a public health care problem due to its high incidence and mortality rates. In this study, we investigated the prevalence of hereditary breast cancer syndromes (HBCS in a population-based cohort in Brazils southernmost capital, Porto Alegre. All participants answered a questionnaire about family history (FH of breast, ovarian and colorectal cancer and those with a positive FH were invited for genetic cancer risk assessment (GCRA. If pedigree analysis was suggestive of HBCS, genetic testing of the BRCA1, BRCA2, TP53, and CHEK2 genes was offered. Of 902 women submitted to GCRA, 214 had pedigrees suggestive of HBCS. Fifty of them underwent genetic testing: 18 and 40 for BRCA1/BRCA2 and TP53 mutation screening, respectively, and 7 for CHEK2 1100delC testing. A deleterious BRCA2 mutation was identified in one of the HBOC probands and the CHEK2 1100delC mutation occurred in one of the HBCC families. No deleterious germline alterations were identified in BRCA1 or TP53. Although strict inclusion criteria and a comprehensive testing approach were used, the suspected genetic risk in these families remains unexplained. Further studies in a larger cohort are necessary to better understand the genetic component of hereditary breast cancer in Southern Brazil.

  6. Rare presentation of familial paraganglioma without evidence of mutation in the SDH, RET and VHL genes: towards further genetic heterogeneity.

    Science.gov (United States)

    Persu, Alexandre; Amyere, Mustapha; Gutierrez-Roelens, Ilse; Rustin, Pierre; Sempoux, Christine; Lecouvet, Frédéric E; Van Beers, Bernard E; Horsmans, Yves; De Plaen, Jean-François; MarcHamoir; Vikkula, Miikka

    2009-01-01

    Mutations in genes encoding succinate dehydrogenase and its anchoring subunits (SDH genes) are at the origin of hereditary head and neck paraganglioma (PGL) and a subset of apparently sporadic pheochromocytoma. We describe a family including three patients harbouring bilateral head and neck PGL diagnosed before 25 years of age. Multiple hypervascular hepatic lesions were subsequently discovered in two of them. In both, liver biopsy confirmed the diagnosis of PGL. In addition, in one patient, MRI disclosed multiple target-like lesions of the spine, highly suggestive of metastatic PGL. Family history was compatible with autosomal dominant inheritance with possible maternal imprinting. Combined single-strand conformation polymorphism and heteroduplex analysis followed by sequencing did not show any mutation of the coding parts of SDHB, SDHC, SDHD, RET or VHL genes. Screening of copy number alterations and loss of heterozygosity in the three affected family members showed no deletion or amplification of the SDH, RET and VHL genes. Furthermore, succinate dehydrogenase activity measured in a liver PGL sample was not significantly decreased in the affected patient as compared with controls, underscoring the exclusion of the SDH genes. To our knowledge, this is the first reported family of hereditary head and neck PGL with metastatic dissemination in the liver and the spine. A large body of evidence supports the absence of mutations in SDH, RET and VHL genes, which suggests the existence of a yet unknown gene at the origin of this particular form of familial PGL.

  7. A diagnostic dilemma following risk-reducing surgery for BRCA1 mutation – a case report of primary papillary serous carcinoma presenting as sigmoid cancer

    Directory of Open Access Journals (Sweden)

    Nash Guy F

    2007-09-01

    Full Text Available Abstract Background Women that carry germ-line mutations for BRCA1 or BRCA2 genes are at an increased risk of developing breast, ovarian and peritoneal cancer. Primary peritoneal carcinoma is a rare tumour histologically identical to papillary serous ovarian carcinoma. Risk-reducing surgery in the form of mastectomy and oophorectomy in premenopausal women has been recommended to prevent breast and ovarian cancer occurrence and decrease the risk of developing primary peritoneal cancer. Case presentation We present a case report of a woman with a strong family history of breast cancer who underwent risk-reducing surgery in the form of bilateral salpingo-oophorectomy following a mastectomy for a right-sided breast tumour. Following the finding of a BRCA1 mutation, a prophylactic left-sided mastectomy was performed. After remaining well for twenty-seven years, she presented with rectal bleeding and altered bowel habit, and was found to have a secondary cancer of the sigmoid colon. She was finally diagnosed with primary papillary serous carcinoma of the peritoneum (PSCP. Conclusion PSCP can present many years after risk-reducing surgery and be difficult to detect. Surveillance remains the best course of management for patients with known BRCA mutations.

  8. Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

    OpenAIRE

    Mehta, Puja; Holder, Susan; Fisher, Benjamin; Vincent, Tonia; Nadesalingam, Kavitha; Hassan, Sadon; D'Cruz, David; Chan, Antoni; Litwic, Anna E.; Seth, Rakhi; McCrae, Fiona; Jury, Elizabeth; Isenberg, David; Karjigi, Uma; Paul, Anupam

    2017-01-01

    Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diag...

  9. Screening for mutations in 17β-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development.

    Science.gov (United States)

    Phelan, Niamh; Williams, Emma L; Cardamone, Stefanie; Lee, Marilyn; Creighton, Sarah M; Rumsby, Gill; Conway, Gerard S

    2015-06-01

    The precise diagnosis of partially virilised women with 46,XY disorders of sex development (DSD) is often obscure. In practice, this group often comes under the poorly defined, clinically based label of partial androgen insensitivity syndrome (PAIS). In a previous study, we found that 5α-reductase 2 (SRD5A2) mutations occurred in 43% of women in this subgroup. We expand this work to include biochemical and genetic screening for 17β-hydroxysteroid dehydrogenase (HSD17B3) and androgen receptor (AR) mutations. Analysis of serum androgens (androstenedione and testosterone) and genetic analyses for HSD17B3 and AR were performed in 42 women from 36 pedigrees with partially virilised 46,XY DSD in whom SRD5A2 deficiency had been excluded by urine steroid profiling. Out of 36 unrelated women, 14 (38%) were found to have HSD17B3 mutations and one (2.7%) to have an AR defect. Six novel pathogenic HSD17B3 mutations were identified: three splice site mutations and three missense changes. Seven patients with HSD17B3 deficiency tested before gonadectomy had basal testosterone/androstenedione (T/A) ratio XY female DSD population and is often associated with lesser degrees of virilisation compared with those with 5α-reductase deficiency. This diagnosis should be considered for individuals labelled as PAIS, particularly, but not exclusively, those who present with virilisation at puberty or primary amenorrhoea. Before gondadectomy, T/A ratio is useful to aid diagnosis, but after gonadectomy sequencing of HSD17B3 must be performed to confirm the diagnosis. © 2015 European Society of Endocrinology.

  10. Phenotypic presentation of thrombophilia in double heterozygote for factor v leiden and prothrombin 20210 G>A mutations: Case report

    Directory of Open Access Journals (Sweden)

    Nagorni-Obradović Ljudmila

    2014-01-01

    Full Text Available Physicians usually do not suspect pulmonary thromboembolism in younger patients except in those who have thrombophilia. In those latter patients some special conditions such as trauma or surgery may provoke the disease. In some adult persons, thrombophilia may still remain unrecognized, until appearance of additional conditions influence development of thrombosis. A 55-year-old Caucasian female, non-smoker, experienced sudden chest pain and hemoptysis without chest trauma. History taking revealed type 2 diabetes mellitus and hypothyroidism. She was overweight with body mass index 29.0. The review of the family history revealed that her father and mother died of brain infarction, while her 22-year-old son and 24-year-old daughter were healthy. Due to suspicion for thrombosis, multi-slice computerized tomography thorax scan was done and pulmonary embolism was diagnosed. Although without clear risk factor for thrombosis in our patient, we performed laboratory investigation for congenital thrombophilia. Genetic analysis showed double heterozygous for factor V Leiden and prothrombin 20210 G>A mutations. Congenital thrombophilia was risk factor for thrombosis in our patient but haemostatic imbalance was not previously clinically recognized. She had two pregnancies without complications. Appearance of other associative factors such as endocrine disorders - hypothyroidism and metabolic syndrome with diabetes type 2, and overweigh were additional potential triggers for clinical manifestation of pulmonary thromboembolism in her adult age. Her children underwent genetic analysis, too. The son was also double heterozygous for factor V Leiden and prothrombin 20210 G>A mutations, while daughter was heterozygous for factor V Leiden, and none had clinical signs of thrombosis. [Projekat Ministarstva nauke Republike Srbije, br. ON175081 i br. ON 175091

  11. Bilateral Cataracts in a 6-year-old with New Onset Diabetes: A novel presentation of a known INS gene mutation

    Science.gov (United States)

    Wasserman, H; Hufnagel, RB; Miraldi, Utz V; Zhang, K; Valencia, CA; Leslie, ND; Crimmins, NA

    2015-01-01

    The prevalence of diabetes-related cataracts during childhood is less than 1%. When cataracts occur, it is often in adolescent females with prolonged symptoms and significant hyperglycemia. Cataracts are not a classic feature of monogenic diabetes. We report a case of a six year old previously healthy Caucasian male who presented with bilateral acquired cataracts and was subsequently diagnosed with new onset diabetes. Additional symptoms at presentation included a several year history of polyuria and polydipsia, mild hepatomegaly, and short stature. Pertinent negatives include acanthosis nigricans, lipoatrophy, deafness, muscle weakness, or neuropathy. HbA1c was significantly elevated at diagnosis (>14%, 129.5mmol/mol) without evidence of ketosis. Autoantibody testing was negative. Features of Mauriac Syndrome (short stature, hepatomegaly) as well as acquired cataracts indicated long standing hyperglycemia with sufficient insulin production to prevent ketone production and development of diabetic ketoacidosis. Whole exome sequencing was conducted and a de novo heterozygous mutation in the INS gene (c.94G>A; p.Gly32Ser) was identified. INS gene mutations are common causes of permanent neonatal diabetes but rare causes of antibody-negative diabetes in children. Importantly, INS gene mutations have not been previous associated with acquired cataracts. Knowledge of a monogenic cause of diabetes allows clinicians to tailor counseling and screening of diabetes related co-morbidities. In summary, this case highlights the need to consider testing for monogenic diabetes, specifically INS gene mutations, in pediatric patients with antibody-negative diabetes, especially if complications of prolonged hyperglycemia are present at diagnosis. PMID:26530398

  12. A Novel Mutation in the Critical P-Box Residue of Steroidogenic Factor-1 Presenting with XY Sex Reversal and Transient Adrenal Failure.

    Science.gov (United States)

    Orekhova, Anna S; Kalinchenko, Natalia; Morozov, Ivan A; Vasilyev, Evgeny V; Rubtsov, Petr M; Dedov, Ivan I; Tiulpakov, Anatoly

    2017-11-17

    Although the importance of steroidogenic factor-1 (SF1, NR5A1) for adrenal development is supported by numerous in vitro and in vivo studies, cases of SF1 deficiency associated with adrenal failure are exceptionally rare. The first human NR5A1 mutation was a heterozygous de novo p.G35E variant identified in a patient with disorder of sex development (DSD) 46,XY and primary adrenal insufficiency. Here we describe another association of the "classic" SF1 phenotype with a novel NR5A1 mutation affecting G35 residue. We describe the clinical characteristics of a phenotypically female patient presenting at 2 months with signs of adrenal insufficiency. DSD 46,XY was diagnosed at 4 years. The NR5A1 gene was analyzed by Sanger sequencing. Minigene splicing and dual luciferase reporter assays were used to characterize effects of the novel mutation on splicing and transcription, respectively. Sequencing of the NR5A1 gene revealed a de novo heterozygous c.104G>A:p.G35D substitution. The minigene experiments demonstrated that c.104G>A substitution did not affect splicing. However, transactivation activity of the p.G35D mutant was clearly impaired, which was comparable with the effect of the p.G35E mutation. The findings stress the importance of G35 residue for adrenal development. The current observation also suggests that some patients with SF1 deficiency may present with transient adrenal failure. © 2017 S. Karger AG, Basel.

  13. Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia.

    Science.gov (United States)

    Chiu, Joanne S; Ma, Lijiang; Wynn, Julia; Krishnan, Usha; Rosenzweig, Erika B; Aspelund, Gudrun; Arkovitz, Marc; Warner, Brad W; Lim, Foong-Yen; Mychaliska, George B; Azarow, Kenneth; Cusick, Robert A; Chung, Dai H; Chung, Wendy K

    2017-01-26

    Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3months of age; moderate of severe PH at 1month of age with death occurring prior to the 3month echocardiogram; or on PH medications at 1month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations. There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes. Prognosis study LEVEL OF EVIDENCE: Level IV. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A Novel Mutation in Human Androgen Receptor Gene Causing Partial Androgen Insensitivity Syndrome in a Patient Presenting with Gynecomastia at Puberty.

    Science.gov (United States)

    Koçyiğit, Cemil; Sarıtaş, Serdar; Çatlı, Gönül; Onay, Hüseyin; Dündar, Bumin Nuri

    2016-06-05

    Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty. It is an X-linked recessive disorder resulting from mutations in the androgen receptor (AR) gene. However, AR gene mutations are found in less than a third of PAIS cases. A 16-year-old boy was admitted with complaints of gynecomastia and sparse facial hair. Family history revealed male relatives from maternal side with similar clinical phenotype. His external genitalia were phenotypically male with pubic hair Tanner stage IV, penoscrotal hypospadias, and a bifid scrotum with bilateral atrophic testes. He had elevated gonadotropins with a normal testosterone level. Chromosome analysis revealed a 46,XY karyotype. Due to the family history suggesting a disorder of X-linked trait, PAIS was considered and molecular analysis of AR gene was performed. DNA sequence analysis revealed a novel hemizygous mutation p.T576I (c.1727C>T) in the AR gene. The diagnosis of PAIS is based upon clinical phenotype and laboratory findings and can be confirmed by detection of a defect in the AR gene. An accurate approach including a detailed family history suggesting an X-linked trait is an important clue for a quick diagnosis.

  15. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention

    DEFF Research Database (Denmark)

    Meur, Gargi; Simon, Albane; Harun, Nasret

    2009-01-01

    quantitated by real-time PCR. RESULTS: A novel coding mutation, L30M, potentially affecting insulin multimerization, was identified in five diabetic individuals (diabetes onset 17-36 years) in a single family. L30M preproinsulin-GFP fluorescence largely associated with the endoplasmic reticulum (ER) in MIN6...... with early-onset diabetes whose clinical presentation is compatible with MODY. These led to the production of (pre)proinsulin molecules with markedly different trafficking properties and effects on ER stress, demonstrating a range of molecular defects in the beta-cell....

  16. Initial comments on the aero geophysical information present at the B and C areas of the Itatira (Brazil) project; Comentarios iniciais sobre as informacoes aerogeofisicas presentes nas areas B e C do Projeto Itatira

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Neivaldo Araujo de; Castelo Branco, Raimundo Mariano Gomes [Ceara Univ., Fortaleza, CE (Brazil). Dept. de Geologia. Lab. de Geofisica de Prospeccao e Sensoriamento Remoto

    1999-07-01

    The aero geophysical project called Itatira,, accomplished by LASA Engenharia e Prospeccoes S.A., Between September and November/1977 through contract with NUCLEBRAS, corresponds to one of the first project of this gender accomplished in national territory. In this project were flight more than 80 000 km of linear lines, which covered approximately 38 000 km{sup 2} on the precambrian terrains of the Ceara State, NE Brazil. For several reasons, the total area of the project was subdivided in three sub-areas (A, B and C), each one covered by a different airship (LAS, 1977). This paper presents the geophysical information and preliminary interpretations of the areas B and C that were obtained through the integrated use of the soft wares AUTOCAD r. 14, OASIS MONTAJ r.4.2 and ERMAPPER r.5.5. (author)

  17. Alternating Hemiplegia of Childhood as a New Presentation of Adenylate Cyclase 5-Mutation-Associated Disease: A Report of Two Cases.

    Science.gov (United States)

    Westenberger, Ana; Max, Christoph; Brüggemann, Norbert; Domingo, Aloysius; Grütz, Karen; Pawlack, Heike; Weissbach, Anne; Kühn, Andrea A; Spiegler, Juliane; Lang, Anthony E; Sperner, Jürgen; Fung, Victor S C; Schallner, Jens; Gillessen-Kaesbach, Gabriele; Münchau, Alexander; Klein, Christine

    2017-02-01

    Mutations in the adenylate cyclase 5 (ADCY5) gene recently have been identified as the cause of a childhood-onset disorder characterized by persistent or paroxysmal choreic, myoclonic, and/or dystonic movements. The 2 novel mutations we identified expand the clinical spectrum of ADCY5 mutations to include alternating hemiplegia of childhood. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever

    Directory of Open Access Journals (Sweden)

    Roberta Caorsi

    2018-01-01

    Full Text Available Primary immunodeficiencies with selective susceptibility to EBV infection are rare conditions associated with severe lymphoproliferation. We followed a patient, son of consanguineous parents, referred to our center for recurrent periodic episodes of fever associated with tonsillitis and adenitis started after an infectious mononucleosis and responsive to oral steroid. An initial diagnosis of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome was done. In the following months, recurrent respiratory infections and episodes of keratitis were also observed, together with a progressive reduction of immunoglobulin levels and an increase of CD20+ cells. Cell sorting and EBV PCR showed 25,000 copies for 100,000 leukocytes with predominant infection of B lymphocytes. Lymph node’s biopsy revealed reactive lymphadenopathy with paracortical involvement consistent with a chronic EBV infection. Molecular analysis of XIAP, SHA2D1A, ITK, and CD27 genes did not detect any pathogenic mutation. The patients underwent repeated courses of anti-CD20 therapy with only a partial control of the disease, followed by stem cell transplantation with a complete normalization of clinical and immunological features. Whole exome sequencing of the trio was performed. Among the variants identified, a novel loss of function homozygous c.163-2A>G mutation of the CD70 gene, affecting the exon 2 AG-acceptor splice site, fit the expected recessive model of inheritance. Indeed, deficiency of both CD27, and, more recently, of its ligand CD70, has been reported as a cause of EBV-driven lymphoproliferation and hypogammaglobulinemia. Cell surface analysis of patient-derived PHA-T cell blasts and EBV-transformed lymphoblastoid cell lines confirmed absence of CD70 expression. In conclusion, we describe a case of severe chronic EBV infection caused by a novel mutation of CD70 presenting with recurrent periodic fever.

  19. Biochemical Education in Brazil.

    Science.gov (United States)

    Vella, F.

    1988-01-01

    Described are discussions held concerning the problems of biochemical education in Brazil at a meeting of the Sociedade Brazileira de Bioquimica in April 1988. Also discussed are other visits that were made to universities in Brazil. Three major recommendations to improve the state of biochemistry education in Brazil are presented. (CW)

  20. The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3.

    Science.gov (United States)

    Qian, Yaping; Johnson, Judith A; Connor, Jessica A; Valencia, C Alexander; Barasa, Nathaniel; Schubert, Jeffery; Husami, Ammar; Kissell, Diane; Zhang, Ge; Weirauch, Matthew T; Filipovich, Alexandra H; Zhang, Kejian

    2014-06-01

    The mutations in UNC13D are responsible for familial hemophagocytic lymphohistiocytosis (FHL) type 3. A 253-kb inversion and two deep intronic mutations, c.118-308C > T and c.118-307G > A, in UNC13D were recently reported in European and Asian FHL3 patients. We sought to determine the prevalence of these three non-coding mutations in North American FHL patients and evaluate the significance of examining these new mutations in genetic testing. We performed DNA sequencing of UNC13D and targeted analysis of these three mutations in 1,709 North American patients with a suspected clinical diagnosis of hemophagocytic lymphohistiocytosis (HLH). The 253-kb inversion, intronic mutations c.118-308C > T and c.118-307G > A were found in 11, 15, and 4 patients, respectively, in which the genetic basis (bi-allelic mutations) explained 25 additional patients. Taken together with previously diagnosed FHL3 patients in our HLH patient registry, these three non-coding mutations were found in 31.6% (25/79) of the FHL3 patients. The 253-kb inversion, c.118-308C > T and c.118-307G > A accounted for 7.0%, 8.9%, and 1.3% of mutant alleles, respectively. Significantly, eight novel mutations in UNC13D are being reported in this study. To further evaluate the expression level of the newly reported intronic mutation c.118-307G > A, reverse transcription PCR and Western blot analysis revealed a significant reduction of both RNA and protein levels suggesting that the c.118-307G > A mutation affects transcription. These specified non-coding mutations were found in a significant number of North American patients and inclusion of them in mutation analysis will improve the molecular diagnosis of FHL3. © 2014 Wiley Periodicals, Inc.

  1. Molecular analysis of β-thalassemia patients: first identification of mutations HBB:c.93-2A>G and HBB:c.114G>A in Brazil.

    Science.gov (United States)

    Fernandes, Andrea Cristina; Shimmoto, Marily Maria Azevedo; Furuzawa, Gilberto Koiti; Vicari, Perla; Figueiredo, Maria Stella

    2011-01-01

    The various clinical phenotypes in β-thalassemias have stimulated the study of genetic factors that could modify the manifestations of these diseases. We examined 21 patients with β-thalassemia (β-thal) in order to identify some genetic modifying factors: β-thalassemia mutations, HBG2:g.-158C>T polymorphism, α-globin gene deletions and (AT)xNz(AT)y motif within the hypersensitive site 2-locus control region (HS2-LCR). In the 42 alleles analyzed, the most frequent mutations observed were HBB:c.92+6T>C (30.9%), HBB:c.118C>T (16.7%), HBB:c.93-21G>A (11.9%) and HBB:c.92+1G>A (4.8%); this finding is in accordance with previous data of the Brazilian population. The other genetic factors analyzed showed no relation with the severity of the disease. For the first time in Brazil, we report HBB:c.93-2A>G and HBB:c.114G>A mutations on the β-globin gene, both in a heterozygous state. This is also the first study to analyze the HS2-LCR in β-thalassemic individuals in the Brazilian population.

  2. A novel point mutation in a class IV glucose-6-phosphate dehydrogenase variant (G6PD São Paulo and polymorphic G6PD variants in São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Raimundo Antonio G. Oliveira

    2009-01-01

    Full Text Available In this study, we used red cell glucose-6-phosphate dehydrogenase (G6PD activity to screen for G6PD-deficient individuals in 373 unrelated asymptomatic adult men who were working with insecticides (organophosphorus and carbamate in dengue prevention programs in 27 cities in São Paulo State, Brazil. Twenty-one unrelated male children suspected of having erythroenzymopathy who were attended at hospitals in São Paulo city were also studied. Fifteen of the 373 adults and 12 of the 21 children were G6PD deficient. G6PD gene mutations were investigated in these G6PD-deficient individuals by using PCR-RFLP, PCR-SSCP analysis and DNA sequencing. Twelve G6PD A-202A/376G and two G6PD Seattle844C, as well as a new variant identified as G6PD São Paulo, were detected among adults, and 11 G6PD A-202A/376G and one G6PD Seattle844C were found among children. The novel mutation c.660C > G caused the replacement of isoleucine by methionine (I220M in a region near the dimer interface of the molecule. The conservative nature of this mutation (substitution of a nonpolar aliphatic amino acid for another one could explain why there was no corresponding change in the loss of G6PD activity (64.5% of normal activity in both cases.

  3. The first Danish family reported with an AQP5 mutation presenting diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type, hyperhidrosis and frequent Corynebacterium infections

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Hetland, Liv Eline; Clemmensen, Ole

    2016-01-01

    in the epidermis of the palms and soles. CASE PRESENTATION: We report the first Danish family diagnosed with diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type in which fourteen individuals are potentially affected. The proband, a 36-year-old male had since childhood been affected by pronounced......BACKGROUND: An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, palmoplantar keratoderma of Bothnian type, is caused by mutations in the AQP5 gene encoding the cell-membrane water channel protein aquaporin 5 leading to defective epidermal-water-barrier function...... recurrent fungal infections, a wellknown feature of the condition, but also periodic worsening with pitted keratolysis and malodour due to bacterial infections. CONCLUSIONS: Palmoplantar keratoderma of Bothnian type, which may be associated with hyperhidrosis, is frequently complicated by fungal infections...

  4. Doenças da mandioquinha-salsa e sua situação atual no Brasil Present situation of arracacha (Arracacia xanthorrhiza diseases in Brazil

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    Gilmar P. Henz

    2002-06-01

    been recorded are described and their current situation in Brazil is discussed. Since its introduction in 1900-1910, arracacha has been considered a non-demanding crop, presenting some minor disease problems, especially when compared to other vegetable crops. Many of the recorded arracacha diseases in Brazil and other Latin American countries are poorly described, for there is hardly any information about pathogenicity tests, pathogen identity, crop losses and environmental conditions affecting diseases. Worldwide, 27 genera of fungi, three of bacteria, nine of nematodes and five species of viruses have been recorded. Of these, thirteen fungi and all bacteria and nematodes were recorded in Brazil. So far, no virus has been recorded, although virus-like symptoms have been observed. The most important diseases are the root knot, caused by Meloidogyne spp., and the postharvest soft rot caused by Erwinia spp. Commonly occurring diseases are leaf spots caused by Septoria spp., Cercospora spp. and Xanthomonas campestris pv. arracaciae, as well as plant rots caused by Sclerotium rolfsii and Sclerotinia sclerotiorum. Viruses could become of great importance since this crop is vegetatively propagated, and part of the plantlets are now being produced in nurseries by a new technique (pre-rooting and then disseminated to different areas throughout Brazil. As there is no pesticide officially registered for this crop in Brazil, preventive measures of control must be used, such as crop rotation, suitable fertilization and irrigation, and removal and destruction of diseased plants. Arracacha seems to be suitable for organic cropping systems, since few diseases are considered limitant.

  5. Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation.

    Science.gov (United States)

    Hasani-Ranjbar, Shirin; Rahmanian, Masoud; Ebrahim-Habibi, Azadeh; Soltani, Akbar; Soltanzade, Akbar; Mahrampour, Elnaz; Amoli, Mahsa M

    2014-06-01

    Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant syndrome. Although thymic carcinoid tumor is recognized as a part of MEN1 syndrome but functioning thymic carcinoid tumor as the first presentation of the MEN1 seems to be very rare. In this report, we present a 29-year-old male who developed ectopic Cushing syndrome secondary to thymic carcinoid tumor and was diagnosed as MEN1 syndrome 2 years later. Further evaluation revealed the presence of carcinoid tumor and other MEN 1 manifestations in several other member of family. Genetic evaluation showed presence of a previously reported mutation in exon 10(R527X) of MEN1 gene in these patients. This presentation showed that thymic neuroendocrine tumor could be the first manifestation of the MEN1 syndrome and it might be diagnosed as a dominant manifestation of this syndrome in a family. We suggest biochemical or genetic screening for MEN-1 syndrome for patients with thymic carcinoid.

  6. Characteristics of sprite and gravity wave convective sources present in satellite IR images during the SpreadFEx 2005 in Brazil

    Directory of Open Access Journals (Sweden)

    F. T. São Sabbas

    2009-03-01

    Full Text Available We developed a technique to identify and estimate the size, intensity, and Tropopause overshoot of thunderstorm convective cores expected to be significant sources of gravity waves. The work was based on GOES IR images of South America on the night of 30 September to 1 October and 25–26 October 2005, as part of the Spread F Experiment (SpreadFEx in Brazil in 2005. We also characterized, for the first time, the convective activity of three small TLE producing thunderstorms that yielded 11 TLEs on 25–26 October 2005. The campaign occurred during the dry to wet season transition in central Brazil, marked by the presence of extra-tropical cyclogenesis over the Atlantic Ocean, and cold fronts penetrating inland. The Tropopause temperature was typically −76°C with a corresponding altitude of ~15 200 m. Vigorous convective cores capable of generating strong gravity waves were located in convective regions having areas with cloud top temperatures ≤−76°C. They had typical cloud-top temperature deficits of ΔT−2.0°C to −8.0°C from the average surroundings, implying overshoot heights of 200 to 3100 m, which are within the typical range. Fast vertical development and high horizontal growth rates were associated with a large number of simultaneously active vigorous convective cores, indicating that their dynamics may have determined the spatial-temporal development of the thunderstorms analyzed. Moderate convective cores were also present in areas with cloud top −76°C≤T≤−70°C. They had ΔT of −1.9°C to −5.3°C producing overshoots between 80–300 m. All convective cores had typical diameters of 5–20 km and their size tended to increase with ΔT, there was a 57% correlation between the two parameters. Analysis of the relationship of cloud top T with positive and negative cloud-to-ground lightning (+/−CG occurrence rate and with peak current showed that lighting activity may provide an independent way to identify

  7. Genotyping of Mycobacterium leprae present on Ziehl-Neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of Brazil

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    Amanda Nogueira Brum Fontes

    2012-12-01

    Full Text Available We analysed 16 variable number tandem repeats (VNTR and three single-nucleotide polymorphisms (SNP in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23, Pernambuco (n = 41, Rio de Janeiro (n = 22 and Rondônia (RO (n = 78. All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1% yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.

  8. A girl with permanent neonatal diabetes due to KCNJ11 mutation presented with Mauriac syndrome after improper adjustment in sulfonylurea dosage over 6 years.

    Science.gov (United States)

    Chai-Udom, Rapeepun; Sahakitrungruang, Taninee; Wacharasindhu, Suttipong; Supornsilchai, Vichit

    2016-09-01

    Mauriac syndrome is characterized by growth impairment, Cushingoid features, and hepatomegaly in patients with poorly controlled type 1 diabetes mellitus (T1DM). We report a novel presentation of Mauriac syndrome in a 9-year-old girl who was diagnosed with neonatal diabetes at 3 months of age due to the p.R201C mutation in KCNJ11. She was initially treated successfully with glipizide at a dose of 0.85 mg/kg/day but after being lost to follow-up and having improper adjustment in dose over many years, the recent dose of 0.6 mg/kg/day appears to have been insufficient for glycemic control but enough to maintain a low level of C-peptide and prevent diabetic ketoacidosis. With proper insulin administration, all presenting clinical characteristics were resolved within 1 month. A review of the literature relating to clinical manifestations of Mauriac syndrome in children with diabetes was performed and included in this report for comparison with our patient. While Mauriac syndrome has been traditionally associated with T1DM, the presence of Mauriac syndrome should not be excluded in other types of diabetes mellitus.

  9. Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

    Science.gov (United States)

    Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

    2018-02-01

    Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

  10. Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study.

    Science.gov (United States)

    Mattos, Beatriz Piva E; Scolari, Fernando Luís; Torres, Marco Antonio Rodrigues; Simon, Laura; Freitas, Valéria Centeno de; Giugliani, Roberto; Matte, Úrsula

    2016-09-01

    Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM). However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country. To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations. Direct DNA sequencing of all encoding regions of three sarcomeric genes was conducted in 43 consecutive individuals of ten unrelated families. Mutations for CMH have been found in 25 (58%) patients of seven (70%) of the ten study families. Fourteen (56%) individuals were phenotype-positive. All mutations were missense, four (66%) in MYH7 and two (33%) in MYBPC3. We have not found mutations in the TNNT2 gene. Mutations in MYH7 were identified in 20 (47%) patients of six (60%) families. Two of them had not been previously described. Mutations in MYBPC3 were found in seven (16%) members of two (20%) families. Two (5%) patients showed double heterozygosis for both genes. The mutations affected different domains of encoded proteins and led to variable phenotypic expression. A family history of HCM was identified in all genotype-positive individuals. In this first genetic-molecular analysis carried out in the south of Brazil, we found mutations in the sarcomeric genes MYH7 and MYBPC3 in 58% of individuals. MYH7-related disease was identified in the majority of cases with mutation. Mutações em genes do sarcômero são encontradas em 60-70% dos indivíduos com formas familiares de cardiomiopatia hipertrófica. (CMH). Entretanto, essa estimativa refere-se a populações de países do hemisfério norte. O perfil genético-molecular da CMH foi tema de poucos estudos no Brasil, particularmente na região sul do país. Realizar a pesquisa de mutações dos genes sarcoméricos MYH

  11. Frontotemporal dementia with parkinsonism linked to chromosome 17 with the MAPT R406W mutation presenting with a broad distribution of abundant senile plaques.

    Science.gov (United States)

    Ishida, Chiho; Kobayashi, Katsuji; Kitamura, Tatsuru; Ujike, Hiroshi; Iwasa, Kazuo; Yamada, Masahito

    2015-02-01

    We report the autopsy results of a patient with familial dementia who was diagnosed as having frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with an R406W mutation in the microtubule-associated protein tau (MAPT) gene. This patient showed Alzheimer's disease (AD)-like clinical manifestations from the age of 59, with reduced β-amyloid1-42 (Aβ42 ) and elevated total and phosphorylated tau levels in the cerebrospinal fluid. He did not present with any apparent parkinsonism throughout the disease course. His autopsy at age 73 showed atrophy and neurodegeneration in many brain regions, particularly in the antero-medial temporal cortex and hippocampus, followed by the frontal lobes, with abundant neurofibrillary tangles. In addition, a diffuse distribution of Aβ-positive senile plaques, including many neuritic plaques, was observed and classified as stage C according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. These results suggest that analyzing of the MAPT gene is essential for diagnosing familial dementia, even if amyloid markers such as Aβ42 in the cerebrospinal fluid and amyloid imaging are positive, or if neuropathological findings indicate a diagnosis of AD. © 2014 Japanese Society of Neuropathology.

  12. Substitution of Aspartate for glycine 1018 in the Type III procollagen (COL3AI) gene causes type IV Ehlers-Danlos Syndrome: The mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother

    Energy Technology Data Exchange (ETDEWEB)

    Kontusaari, S.; Tromp, G.; Kuivaniemi, H.; Prockop, D.J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Stolle, C. (Robert Wood Johnson Medical School, Piscataway, NJ (United States)); Pope, F.M.

    1992-09-01

    A proband with arterial ruptures and skin changes characteristic of the type IV variant of Ehlers-Danlos syndrome was found to have a single-base mutation in the type III procollagen gene, which converted the codon for glycine at amino position 1018 to a codon for aspartate. (Amino acid positions are numbered by the standard convention in which the first glycine of the triple-helical domain of an [alpha] chain is number 1. The numbers of positions in the [alpha]1(III) chains can be converted to positions in the human pro[alpha](III) chain by adding 167.). Nucleotide sequencing of overlapping PCR products in which the two alleles were distinguished demonstrated that the mutation of glycine 1018 was the only mutation that changed the primary structure of type III procollagen. The glycine substitution markedly decreased the amount of type III procollagen secreted into the medium by cultured skin fibroblasts from the proband. It is surprising that the same mutation was found in about 94% of the peripheral blood leukocytes from the proband's asymptomatic 72-year-old mother. Other tissues from the mother contained the mutated allele; it was present in 0%-100% of different samples of hair cells and in about 40% of cells from the oral epithelium. Therefore, the mother was a mosaic for the mutation. Since the mutated allele was present in cells derived from all three germ layers, the results indicated that the mutation arose by the late blastocyst stage of development. The results also indicate that assays of blood leukocytes do not always reveal mosaicism or predict phenotypic involvement of tissues, such as blood vessels, that are derived from the same embryonic cells as are leukocytes. 66 refs., 6 figs., 1 tab.

  13. Quality of life, anxiety and depression in patients with HIV/AIDS who present poor adherence to antiretroviral therapy: a cross-sectional study in Salvador, Brazil

    Directory of Open Access Journals (Sweden)

    Mónica Narváez Betancur

    Full Text Available Abstract The introduction of highly active antiretroviral therapy marked a major gain in efficacy of HIV/AIDS treatment and a reduction in morbidity and mortality of the infected patients. However, high levels of adherence are required to obtain virologic suppression. In Brazil, the policy of free and universal access to antiretroviral therapy has been in place since 1996, although there are reports of poor adherence. Objective To define the clinical, demographic and psychological characteristics, and quality of life of patients with HIV/AIDS who present poor adherence to highly active antiretroviral therapy. Methods This was a cross-sectional study. To be included in the study patients had to be 18 through 65 years old, diagnosed with HIV/AIDS, having the two previous viral loads above 500 copies, a surrogate for poor adherence to antiretrovirals. The following instruments were applied to all eligible patients: the sociodemographic questionnaire “Adherence Follow-up Questionnaire”, the Beck Depression Inventory (BDI-II, the Beck Anxiety Inventory (BAI, and the 36-Item Short Form Survey. Results 47 patients were evaluated, 70.2% were female, mean age of 41.9 years (±10.5, 46.8% were single, 51.1% self-reported adherence ≥95%, 46.8% mentioned depression as the main reason for not taking the medication, 59.5% presented symptoms of moderate to severe depression, and 44.7% presented symptoms of moderate to severe anxiety. Finally, regarding health-related quality of life these patients obtained low scores in all dimensions, physical component summary of 43.96 (±9.64 and mental component summary of 33.19 (±13.35. Conclusion The psychological component is considered to be fundamental in the management of HIV/AIDS patients. Psychoeducation should be conducted at the initial evaluation to reduce negative beliefs regarding antiretroviral therapy Assessment of anxiety and depression symptoms should be done throughout therapy as both psycological

  14. Quality of life, anxiety and depression in patients with HIV/AIDS who present poor adherence to antiretroviral therapy: a cross-sectional study in Salvador, Brazil.

    Science.gov (United States)

    Betancur, Mónica Narváez; Lins, Liliane; Oliveira, Irismar Reis de; Brites, Carlos

    The introduction of highly active antiretroviral therapy marked a major gain in efficacy of HIV/AIDS treatment and a reduction in morbidity and mortality of the infected patients. However, high levels of adherence are required to obtain virologic suppression. In Brazil, the policy of free and universal access to antiretroviral therapy has been in place since 1996, although there are reports of poor adherence. To define the clinical, demographic and psychological characteristics, and quality of life of patients with HIV/AIDS who present poor adherence to highly active antiretroviral therapy. This was a cross-sectional study. To be included in the study patients had to be 18 through 65 years old, diagnosed with HIV/AIDS, having the two previous viral loads above 500 copies, a surrogate for poor adherence to antiretrovirals. The following instruments were applied to all eligible patients: the sociodemographic questionnaire "Adherence Follow-up Questionnaire", the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), and the 36-Item Short Form Survey. 47 patients were evaluated, 70.2% were female, mean age of 41.9 years (±10.5), 46.8% were single, 51.1% self-reported adherence ≥95%, 46.8% mentioned depression as the main reason for not taking the medication, 59.5% presented symptoms of moderate to severe depression, and 44.7% presented symptoms of moderate to severe anxiety. Finally, regarding health-related quality of life these patients obtained low scores in all dimensions, physical component summary of 43.96 (±9.64) and mental component summary of 33.19 (±13.35). The psychological component is considered to be fundamental in the management of HIV/AIDS patients. Psychoeducation should be conducted at the initial evaluation to reduce negative beliefs regarding antiretroviral therapy Assessment of anxiety and depression symptoms should be done throughout therapy as both psycological conditions are associated with patient adherence, success of

  15. Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.

    Science.gov (United States)

    Nakamura, Akinori; Fueki, Noboru; Shiba, Naoko; Motoki, Hirohiko; Miyazaki, Daigo; Nishizawa, Hitomi; Echigoya, Yusuke; Yokota, Toshifumi; Aoki, Yoshitsugu; Takeda, Shin'ichi

    2016-07-01

    Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene.

  16. The sodium-phosphate co-transporter SLC34A2, and pulmonary alveolar microlithiasis: Presentation of an inbred family and a novel truncating mutation in exon 3.

    Science.gov (United States)

    Vismara, Marco Favio Michele; Colao, Emma; Fabiani, Fernanda; Bombardiere, Francesco; Tamburrini, Oscar; Alessio, Caterina; Manti, Francesco; Pelaia, Gerolamo; Romeo, Pasquale; Iuliano, Rodolfo; Perrotti, Nicola

    2015-01-01

    Pulmonary alveolar microlithiasis is a disorder in which many tiny fragments (microliths) of calcium phosphate gradually accumulate in alveoli. Loss of function mutations in the gene SLC34A2 coding for the sodium phosphate co-transporter (NaPi-IIb) are responsible for genetic forms of alveolar microlithiasis. We now report a consanguineous Italian family from Calabria with two affected members segregating alveolar microlithiasis in a recessive fashion. We describe, for the first time, a novel loss of function mutation in the gene coding for NaPi-IIb. A careful description of the clinical phenotype is provided together with technical details for direct sequencing of the gene.

  17. BRCA1 mutations in Brazilian patients

    Directory of Open Access Journals (Sweden)

    Juliano Javert Lourenço

    2004-01-01

    Full Text Available BRCA1 mutations are known to be responsible for the majority of hereditary breast and ovarian cancers in women with early onset and a family history of the disease. In this paper we present a mutational survey conducted in 47 Brazilian patients with breast/ovarian cancer, selected based on age at diagnosis, family history, tumor laterality, and presence of breast cancer in male patients. All 22 coding exons and intron-exon junctions were sequenced. Constitutional mutations were found in seven families, consisting of one insertion (insC5382 in exon 20 (four patients, one four base-pair deletion (3450-3453delCAAG in exon 11 resulting in a premature stop codon (one patient, one transition (IVS17+2T> C in intron 17 affecting a mRNA splicing site (one patient, and a C> T transition resulting in a stop-codon (Q1135X in exon 11 (one patient. The identification of these mutations which are associated to hereditary breast and ovarian cancers will contribute to the characterization of the mutational spectrum of BRCA1 and to the improvement of genetic counseling for familial breast/ovarian cancer patients in Brazil.

  18. Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil.

    Science.gov (United States)

    Moreira-Nunes, Caroline Aquino; Barros, Mariceli Baia Leão; do Nascimento Borges, Bárbara; Montenegro, Raquel Carvalho; Lamarão, Leticia Martins; Ribeiro, Helem Ferreira; Bona, Amanda Braga; Assumpção, Paulo Pimentel; Rey, Juan Antonio; Pinto, Giovanny Rebouças; Burbano, Rommel Rodriguez

    2014-01-01

    Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil. Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern. No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents. This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study.

  19. The sodium-phosphate co-transporter SLC34A2, and pulmonary alveolar microlithiasis: Presentation of an inbred family and a novel truncating mutation in exon 3

    Directory of Open Access Journals (Sweden)

    Marco Favio Michele Vismara

    2015-01-01

    We now report a consanguineous Italian family from Calabria with two affected members segregating alveolar microlithiasis in a recessive fashion. We describe, for the first time, a novel loss of function mutation in the gene coding for NaPi-IIb. A careful description of the clinical phenotype is provided together with technical details for direct sequencing of the gene.

  20. Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB

    NARCIS (Netherlands)

    Wolach, Baruch; Scharf, Yitshak; Gavrieli, Ronit; de Boer, Martin; Roos, Dirk

    2005-01-01

    Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91(phox), a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme

  1. Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H in a French Family

    Directory of Open Access Journals (Sweden)

    Agnès Jacquin

    2013-10-01

    Full Text Available Introduction: Inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD is a rare late-onset autosomal dominant disorder due to a mutation of the valosin-containing protein (VCP gene. Case Report: We report the case of a patient who developed progressive weakness of the limbs in his fifties, until he was confined to a wheelchair. At that time, he developed acute behavioural changes including irritability, severe anxiety and major depression, which led to him being hospitalised in a psychiatric hospital. He also suffered from aphasia and executive function impairment, which helped us to diagnose a behavioural form of frontotemporal dementia (FTD. The diagnosis of IBMPFD due to a mutation in the VCP gene was confirmed by a genetic study of the VCP gene (R155H mutation. Discussion: The clinical diagnosis of IBMPFD is suggested by the presence of at least one of three major manifestations as follows: inclusion body myopathy (mean onset at 42 years of age, Paget's disease of the bone and FTD (mean onset at 55 years of age. It is mostly the behavioural form of FTD (behavioural changes, executive dysfunction and aphasia. One interesting finding in our report is the predominance of the psychiatric symptoms at the beginning of the behavioural changes, which led to the diagnosis of FTD. The diagnosis of IBMPFD was confirmed by the genetic study: the R155H mutation found on exon 5 domain CDC48 is the most frequent of the 18 known mutations in the VCP gene.

  2. The impact of the H1N1 influenza pandemic on clinical presentations and viral epidemiology of acute respiratory infection in preschool children in Brazil.

    Science.gov (United States)

    Fawkner-Corbett, David W; Duarte, Maria Carmo M B; Rose, Katie; Fonceca, Angela; Bezerra, Patricia; Hopkins, Mark; Britto, Murilo; Cuevas, Luis E; Correia, Jailson B; McNamara, Paul Stephen

    2012-06-01

    We assessed the impact of the H1N1 influenza pandemic on acute respiratory infection in young children from low-income families in Brazil. Influenza (specifically H1N1) detection in acute respiratory infection quintupled during the pandemic and, during its peak, it was associated with 30% of all acute respiratory infection visits to the emergency department. H1N1 was also associated with increased risk of hospitalization and coinfection.

  3. A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences.

    Science.gov (United States)

    Shea, Yat-Fung; Chu, Leung-Wing; Chan, Angel On-Kei; Ha, Joyce; Li, Yan; Song, You-Qiang

    2016-02-01

    There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites. Copyright © 2015. Published by Elsevier B.V.

  4. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

    Directory of Open Access Journals (Sweden)

    Danielle P. Porter

    2015-12-01

    Full Text Available At Week 96 of the Single-Tablet Regimen (STaR study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF developed resistance mutations compared to those treated with efavirenz (EFV/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33, as well as baseline samples from control subjects with virologic response (n = 118. Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20% were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  5. A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

    Science.gov (United States)

    Martínez, Luz Maira Wintaco; Castro, Gloria Puerto; Guerrero, Martha Inírida

    2016-01-01

    Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in therpoB, katG, inhA,ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 forrpoB, katG, inhA,ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours. PMID:26841047

  6. A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Luz Maira Wintaco Martínez

    2016-02-01

    Full Text Available Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR and extensively drug-resistant TB based on single nucleotide polymorphism (SNP mutations present in therpoB, katG, inhA,ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 forrpoB, katG, inhA,ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours.

  7. HIV-1 subtypes and mutations associated to antiretroviral drug resistance in human isolates from Central Brazil Subtipos e mutações associadas à resistência aos anti-retrovirais em isolados de HIV-1 do Distrito Federal

    Directory of Open Access Journals (Sweden)

    Daniela Marreco Cerqueira

    2004-09-01

    Full Text Available The detection of polymorphisms associated to HIV-1 drug-resistance and genetic subtypes is important for the control and treatment of HIV-1 disease. Drug pressure selects resistant variants that carry mutations in the viral reverse transcriptase (RT and protease (PR genes. For a contribution to the public health authorities in planning the availability of therapeutic treatment, we therefore described the genetic variability, the prevalence of mutations associated to drug resistance and the antiretroviral resistance profile in HIV-1 isolates from infected individuals in Central Brazil. Nineteen HIV-1 RNA samples from a Public Health Laboratory of the Federal District were reversely transcribed and cDNAs were amplified by nested PCR. One fragment of 297 bp coding the entire protease gene, and another of 647 bp, corresponding to the partial RT gene (codons 19-234, were obtained. Automated sequencing and BLAST analysis revealed the presence of 17 B and 2 F1 HIV-1 subtypes. The amino acid sequences were analyzed for the presence of resistance-associated mutations. A total of 6 PR mutations, 2 major and 4 accessory, and 8 RT mutations related to drug resistance were found. Our data suggest a high prevalence of HIV-1 B subtype in the studied population of Federal District as well as the presence of genetically-resistant strains in individuals failing treatment.A detecção de polimorfismos do HIV-1 que estejam associados à resistência às drogas anti-retrovirais e aos subtipos genéticos é importante para o controle e tratamento da infecção pelo HIV-1. A pressão exercida pela terapia anti-retroviral seleciona variantes resistentes com mutações nos genes virais da transcriptase reversa (RT e da protease (PR. Assim, visando contribuir com as autoridades de saúde pública na perspectiva de planejar a disponibilidade de um tratamento terapêutico, nós descrevemos a variabilidade genética e a prevalência de mutações associadas à resist

  8. Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus

    Science.gov (United States)

    Lv, Zhan-Yun; Xu, Xue-Mei; Cao, Xiao-Fu; Wang, Qian; Sun, Da-Fang; Tian, Wen-Jing; Yang, Yan; Wang, Yu-Zhong; Hao, Yan-Lei

    2017-01-01

    Abstract Rationale: Chronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterized by bilateral progressive ptosis and ophthalmoplegia. Kearns -Sayre syndrome (KSS) is a multisystem disorder with PEO, cardiac conduction block, and pigmentary retinopathy. A few individuals with CPEO have other manifestations of KSS, but do not meet all the clinical diagnosis criteria, and this is called “CPEO plus.” Patient concerns: We report a 48-year-old woman exhibiting limb weakness, ptosis, ophthalmoparesis, and cerebellar dysfunctions. Diagnoses: The patient was diagnosed as exhibiting CPEO plus syndrome. Interventions: The patient underwent clinical, genetic, histological, and histochemical analysis. She was treated orally with CoQ10, vitamin Bs, L-carnitine, and vitamin E. Outcomes: The patient's serum creatine kinase levels, electrocardiography, and nerve conduction study results were normal; an electromyogram revealed myopathic findings. Magnetic resonance imaging showed global brain atrophy, particularly in the brainstem and cerebellum areas. A muscle biopsy showed the presence of abundant ragged red fibers. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed C960del mutation in 12S rRNA and homozygous mutation C2835T in 16S rRNA. She took medicines on schedule, the clinical features were similar as 2 years ago. Lessons: This is the first report of 2 rRNA mutations in a patient with MRI findings showing global brain atrophy, particularly in brainstem and cerebellum areas. Early recognition and appropriate treatment is crucial. This case highlights the cerebellar ataxia can occur in CPEO plus.

  9. Mutations in Genes Encoding Cardiac Ion Channels Previously Associated With Sudden Infant Death Syndrome (SIDS) Are Present With High Frequency in New Exome Data

    DEFF Research Database (Denmark)

    Andreasen, Charlotte Hartig; Refsgaard, Lena; Nielsen, Jonas B

    2013-01-01

    National Heart, Lung, and Blood Institute Grand Opportunity (NHLBI GO) Exome Sequencing Project (ESP) provided important knowledge on genetic variation in the background population. Our aim was to identify all variants previously associated with SIDS in ESP to improve the discrimination between plausible......Sudden infant death syndrome (SIDS) is the leading cause of death in the first 6 months after birth in the industrialized world. The genetic contribution to SIDS has been investigated intensively and to date, 14 cardiac channelopathy genes have been associated with SIDS. Newly published data from...... disease-causing mutations and variants most likely to be false-positive....

  10. Multiple Hepatitis B Virus (HBV) Quasispecies and Immune-Escape Mutations Are Present in HBV Surface Antigen and Reverse Transcriptase of Patients With Acute Hepatitis B.

    Science.gov (United States)

    Aragri, Marianna; Alteri, Claudia; Battisti, Arianna; Di Carlo, Domenico; Minichini, Carmine; Sagnelli, Caterina; Bellocchi, Maria Concetta; Pisaturo, Maria Antonietta; Starace, Mario; Armenia, Daniele; Carioti, Luca; Pollicita, Michela; Salpini, Romina; Sagnelli, Evangelista; Perno, Carlo Federico; Coppola, Nicola; Svicher, Valentina

    2016-06-15

    This study characterizes and defines the clinical value of hepatitis B virus (HBV) quasispecies with reverse transcriptase and HBV surface antigen (HBsAg) heterogeneity in patients with acute HBV infection. Sixty-two patients with acute HBV infection (44 with genotype D infection and 18 with genotype A infection) were enrolled from 2000 to 2010. Plasma samples obtained at the time of the first examination were analyzed by ultradeep pyrosequencing. The extent of HBsAg amino acid variability was measured by Shannon entropy. Median alanine aminotransferase and serum HBV DNA levels were 2544 U/L (interquartile range, 1938-3078 U/L) and 5.88 log10 IU/mL (interquartile range, 4.47-7.37 log10 IU/mL), respectively. Although most patients serologically resolved acute HBV infection, only 54.1% developed antibody to HBsAg (anti-HBs). A viral population with ≥1 immune-escape mutation was found in 53.2% of patients (intrapatient prevalence range, 0.16%-100%). Notably, by Shannon entropy, higher genetic variability at HBsAg amino acid positions 130, 133, and 157 significantly correlated with no production of anti-HBs in individuals infected with genotype D (P < .05). Stop codons were detected in 19.3% of patients (intrapatient prevalence range, 1.6%-47.5%) and occurred at 11 HBsAg amino acid positions, including 172 and 182, which are known to increase the oncogenic potential of HBV.Finally, ≥1 drug resistance mutation was detected in 8.1% of patients (intrapatient prevalence range, 0.11%-47.5% for primary mutations and 10.5%-99.9% for compensatory mutations). Acute HBV infection is characterized by complex array of viral quasispecies with reduced antigenicity/immunogenicity and enhanced oncogenic potential. These viral variants may induce difficult-to-treat HBV forms; favor HBV reactivation upon iatrogenic immunosuppression, even years after infection; and potentially affect the efficacy of the current HBV vaccination strategy. © The Author 2016. Published by Oxford

  11. Population and mutation analysis of Y-STR loci in a sample from the city of São Paulo (Brazil

    Directory of Open Access Journals (Sweden)

    José A. Soares-Vieira

    2008-01-01

    Full Text Available The haplotypes of seven Y-chromosome STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, and DYS393 were determined in a sample of 634 healthy Brazilian males (190 adult individuals and 222 father-son pairs. The 412 adults were unrelated, and the 222 father-son pairs had their biological relationship confirmed using autosomal STRs (LR > 10,000. Among the 412 adults, a total of 264 different 7-loci haplotypes were identified, 210 of which were unique. The most frequent haplotype was detected in 31 instances, occurring with a frequency of 7.52%. The haplotype diversity index was calculated as 98.83%. Upon transmission of the 1,554 alleles, in 222 father-son pairs, six mutations were observed, with an average overall rate of 3.86 x 10-3 per locus. A haplotype with a duplicated DYS389I locus, and another with duplicated DYS389I, DYS389II, and DYS439 loci were detected in both fathers and their respective sons.

  12. Atypical juvenile presentation of GM2 gangliosidosis AB in a patient compound-heterozygote for c.259G>T and c.164C>T mutations in the GM2A gene

    Directory of Open Access Journals (Sweden)

    Carla Martins

    2017-06-01

    Full Text Available GM2-gangliosidosis, AB variant is an extremely rare autosomal recessive inherited disorder caused by mutations in the GM2A gene that encodes GM2 ganglioside activator protein (GM2AP. GM2AP is necessary for solubilisation of GM2 ganglioside in endolysosomes and its presentation to β-hexosaminidase A. Conversely GM2AP deficiency impairs lysosomal catabolism of GM2 ganglioside, leading to its storage in cells and tissues. We describe a 9-year-old child with an unusual juvenile clinical onset of GM2-gangliosidosis AB. At the age of 3 years he presented with global developmental delay, progressive epilepsy, intellectual disability, axial hypertonia, spasticity, seizures and ataxia, but without the macular cherry-red spots typical for GM2 gangliosidosis. Brain MRI detected a rapid onset of diffuse atrophy, whereas whole exome sequencing showed that the patient is a compound heterozygote for two mutations in GM2A: a novel nonsense mutation, c.259G>T (p.E87X and a missense mutation c.164C>T (p.P55L that was recently identified in homozygosity in patients of a Saudi family with a progressive chorea-dementia syndrome. Western blot analysis showed an absence of GM2AP in cultured fibroblasts from the patient, suggesting that both mutations interfere with the synthesis and/or folding of the protein. Finally, impaired catabolism of GM2 ganglioside in the patient's fibroblasts was demonstrated by metabolic labeling with fluorescently labeled GM1 ganglioside and by immunohistochemistry with anti-GM2 and anti-GM3 antibodies. Our observation expands the molecular and clinical spectrum of molecular defects linked to GM2-gangliosidosis and suggests novel diagnostic approach by whole exome sequencing and perhaps ganglioside analysis in cultured patient's cells.

  13. Eand P opportunities in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Castilho, Marcelo [National Petroleum Agency of Brasil (Brazil)

    2011-07-01

    Brazil is one of the world's largest economies and the country also has significant heavy oil reserves. This report from the National Petroleum Agency of Brazil aims at presenting the situation of the oil and gas sector in Brazil in terms of resources, production, regulatory framework and opportunities for the future. Brazil has numerous sedimentary basins at its disposal, most of them being prospected by both national and foreign companies from all over the world. Brazil has over 14 billion barrels of proven reserves, its production is 2,1 MMBbl/d and heavy oil represents almost 40% of that production. The National Petroleum Agency of Brazil is responsible for the implementation of oil sector policy with the aims of maintaining self-sufficiency, implementing good practices in terms of health and safety, and increasing local content. This paper pointed out that Brazil has an important opportunity to enhance its energy sector through the development of heavy oil.

  14. Focus on Brazil

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-11-01

    Brazil, the largest country in South America with a population of almost 140 million, has been plagued since the early 1980s by high foreign debt (approximately US$121 billion at present) and hyperinflation (nearly 600 percent over the past 12 months). These factors, in combination with the slower than anticipated growth in electricity demand, have been instrumental in curtailing nuclear power development in the country. Following recommendations advanced in a commissioned study for improving Brazil`s nuclear program, Brazilian President Jose Sarney announced on August 31st the restructuring of the country`s nuclear industry.

  15. Hemoglobin (Hb) Val de Marne (Hb Footscray) in Brazil: the first case report.

    Science.gov (United States)

    Okumura, J V; Shimauti, E L T; Silva, D G H; Torres, L S; Belini-Junior, E; Oliveira, R G; Patussi, E V; Herrero, J C M; Bonini-Domingos, C R

    2016-07-14

    Hemoglobin (Hb) variants involving alpha-chains are less common in the global population than Hb variants resulting from beta-chain alterations. Generally, alpha-chain Hb variants are caused by point mutations affecting alpha-1 and/or alpha-2 genes of the alpha-globin cluster (HBA1 and HBA2). In Brazil, the most prevalent alpha-chain Hb variant is Hb Hasharon. In this study, we present the first case of an Hb Val de Marne variant in the Americas, specifically in Brazil.

  16. Audit Quality in Brazil: A Study of the Judgment of the Independent Auditors on Adoption of the Adjustment to Present Value in Construction and Engineering Companies Listed on BM&F-Bovespa

    Directory of Open Access Journals (Sweden)

    Felipe da Silva Moreira

    2015-04-01

    Full Text Available Audit quality is a complex issue and difficult to measure on the audit quality level in the Brazilian stock exchange. Most of the companies listed on the on the stock exchange are audited by companies called the Big Four and in this context, the market assigns to them pretext of higher quality in their performances when compared with the non-Big Four companies. In Brazil, recent financial scandals while international accounting and auditing standards were been adopted. This provides an opportunity to analyze the adequacy of audit services to the convergence process. Given the scenario, the problem arises: Have the audit firms uniform quality, based on the technical criteria of their judgment when the proper adoption of CPC 12 – adjustment to present value by Brazilian listed companies? The objective of this study is to investigate the uniformity in the quality of services performed by audit firms in Brazil about Brazilian listed companies based on adoption to CVM deliberation number 564/08. This paper consists on the analysis of the accounting reports, reference form and the Auditors of the companies of the construction and engineering sector in years 2010 and 2011, revealing among its main findings the absence of uniform quality in the independent auditor’s report based on the adoption to the adjustment to present value.

  17. Founder effect of the BRCA1 5382insC mutation in Brazilian patients with hereditary breast ovary cancer syndrome.

    Science.gov (United States)

    da Costa, E C B; Vargas, F R; Moreira, A S; Lourenço, J J; Caleffi, M; Ashton-Prolla, P; Martins Moreira, M A M

    2008-07-01

    The 5382insC mutation in BRCA1 is a frequently reported mutation, being very prevalent in Central and Eastern Europe. This mutation was recurrently reported in Brazil and one case was reported Portugal, but not in Spain and other South-American countries,. We analyzed the haplotypic profile of seven Brazilian carriers of 5382insC to characterize a possible founder effect. The analyses indicated that mutation carriers shared an identical haplotype. The absence of this mutation in Spain, other South American countries, and sub-Saharan populations, as well as the patients' own ancestry, point to a significant Central or Eastern European contribution to the present genetic background of Brazilian population, different from the population structuring of remaining South American countries.

  18. A Novel Mutation in Human Androgen Receptor Gene Causing Partial Androgen Insensitivity Syndrome in a Patient Presenting with Gynecomastia at Puberty

    National Research Council Canada - National Science Library

    Koçyiğit, Cemil; Sarıtaş, Serdar; Çatlı, Gönül; Onay, Hüseyin; Dündar, Bumin Nuri

    2016-01-01

    Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty...

  19. A Novel Mutation in Human Androgen Receptor Gene Causing Partial Androgen Insensitivity Syndrome in a Patient Presenting with Gynecomastia at Puberty

    National Research Council Canada - National Science Library

    Cemil Koçyigit; Serdar Saritas; Gönül Çatli; Hüseyin Onay; Bumin Nuri Dündar

    2016-01-01

      Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty...

  20. Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

    OpenAIRE

    Bossi, Grazia; Giordano, Giuseppe; Rispoli, Gaetana Anna; Maggiore, Giuseppe; Naturale, Mauro; Marchetti, Daniela; Iascone, Maria

    2017-01-01

    We report definitive diagnosis and effective treatment with oral cholic acid in one Italian male child affected by 3β- hydroxy-Δ5-C27-steroid dehydrogenase (3β- HSD) deficiency. He presented with failure to thrive, hepatomegaly and multiple cystic images in kidneys; no biochemical evidence of cholestasis. Large amounts of bile acid metabolites was detected in urine by fast atom bombardment ionization mass spectrometry (FAB-MS). HSDH3B7 gene analysis identified one mutation in intron 4, at nuc...

  1. Lycopodiaceae in Brazil. Conspectus of the family

    DEFF Research Database (Denmark)

    Øllgaard, Benjamin; Windisch, Paulo G.

    2014-01-01

    A conspectus of the Lycopodiaceae in Brazil is presented, following a generic classification based on anatomy, chromosome numbers, spores and gametophytes, as well as recent molecular studies. The species of Lycopodiaceae occurring in Brazil, traditionally treated conservatively, were grouped in ...

  2. Mitochondrial mutations in cancer.

    Science.gov (United States)

    Brandon, M; Baldi, P; Wallace, D C

    2006-08-07

    The metabolism of solid tumors is associated with high lactate production while growing in oxygen (aerobic glycolysis) suggesting that tumors may have defects in mitochondrial function. The mitochondria produce cellular energy by oxidative phosphorylation (OXPHOS), generate reactive oxygen species (ROS) as a by-product, and regulate apoptosis via the mitochondrial permeability transition pore (mtPTP). The mitochondria are assembled from both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) genes. The mtDNA codes for 37 genes essential of OXPHOS, is present in thousands of copies per cell, and has a very high mutations rate. In humans, severe mtDNA mutations result in multisystem disease, while some functional population-specific polymorphisms appear to have permitted humans to adapt to new environments. Mutations in the nDNA-encoded mitochondrial genes for fumarate hydratase and succinate dehydrogenase have been linked to uterine leiomyomas and paragangliomas, and cancer cells have been shown to induce hexokinase II which harnesses OXPHOS adenosine triphosphate (ATP) production to drive glycolysis. Germline mtDNA mutations at nucleotides 10398 and 16189 have been associated with breast cancer and endometrial cancer. Tumor mtDNA somatic mutations range from severe insertion-deletion and chain termination mutations to mild missense mutations. Surprisingly, of the 190 tumor-specific somatic mtDNA mutations reported, 72% are also mtDNA sequence variants found in the general population. These include 52% of the tumor somatic mRNA missense mutations, 83% of the tRNA mutations, 38% of the rRNA mutations, and 85% of the control region mutations. Some associations might reflect mtDNA sequencing errors, but analysis of several of the tumor-specific somatic missense mutations with population counterparts appear legitimate. Therefore, mtDNA mutations in tumors may fall into two main classes: (1) severe mutations that inhibit OXPHOS, increase ROS production and promote tumor

  3. Measurement of ampere-hour for small consumers in Brazil: present status and trends; Medicao de ampere-hora para pequenos consumidores no Brasil: estado atual e perspectivas

    Energy Technology Data Exchange (ETDEWEB)

    Alves Junior, J.E.R.; Lippincott, M.; Caldas, R.P.; Costa, R.S. de; Alvarenga, L.M.; Loureiro, M.R.B.; Luiz, F.C. [Centro de Pesquisas de Energia Eletrica, Rio de Janeiro, RJ (Brazil). E-mail: alves@cepel.br; Santos, C.; Araujo, P. [Centrais Eletricas de Pernambuco (CELPE), Recife, PE (Brazil); Pinho, A. [Centrais Eletricas do Para (CELPA), Belem, PA (Brazil); Marcondes, P. [Daruma Telecomunicacoes e Informatica S.A., Sao Paulo, SP (Brazil); Vidal, J.C.M. [APEL Aplicacoes Eletronicas Industria e Comercio Ltda., Campina Grande, PB (Brazil); Peyro, R.J. [Telematica, Sao Paulo, SP (Brazil)

    1999-07-01

    This paper presents a description of the ampere-hour meter developed with the CEPEL technology. This meter aims to the economic optimization of the measurement and invoicing or the small scale consumer electric power consumption. The paper presents the description, the technical and construction characteristics, the invoicing system and the using by the electric power utilities.

  4. First insight into the somatic mutation burden of neurofibromatosis type 2-associated grade I and grade II meningiomas: a case report comprehensive genomic study of two cranial meningiomas with vastly different clinical presentation.

    Science.gov (United States)

    Dewan, Ramita; Pemov, Alexander; Dutra, Amalia S; Pak, Evgenia D; Edwards, Nancy A; Ray-Chaudhury, Abhik; Hansen, Nancy F; Chandrasekharappa, Settara C; Mullikin, James C; Asthagiri, Ashok R; Heiss, John D; Stewart, Douglas R; Germanwala, Anand V

    2017-02-13

    Neurofibromatosis type 2 (NF2) is a rare autosomal dominant nervous system tumor predisposition disorder caused by constitutive inactivation of one of the two copies of NF2. Meningiomas affect about one half of NF2 patients, and are associated with a higher disease burden. Currently, the somatic mutation landscape in NF2-associated meningiomas remains largely unexamined. Here, we present an in-depth genomic study of benign and atypical meningiomas, both from a single NF2 patient. While the grade I tumor was asymptomatic, the grade II tumor exhibited an unusually high growth rate: expanding to 335 times its initial volume within one year. The genomes of both tumors were examined by whole-exome sequencing (WES) complemented with spectral karyotyping (SKY) and SNP-array copy-number analyses. To better understand the clonal composition of the atypical meningioma, the tumor was divided in four sections and each section was investigated independently. Both tumors had second copy inactivation of NF2, confirming the central role of the gene in meningioma formation. The genome of the benign tumor closely resembled that of a normal diploid cell and had only one other deleterious mutation (EPHB3). In contrast, the chromosomal architecture of the grade II tumor was highly re-arranged, yet uniform among all analyzed fragments, implying that this large and fast growing tumor was composed of relatively few clones. Besides multiple gains and losses, the grade II meningioma harbored numerous chromosomal translocations. WES analysis of the atypical tumor identified deleterious mutations in two genes: ADAMTSL3 and CAPN5 in all fragments, indicating that the mutations were present in the cell undergoing fast clonal expansion CONCLUSIONS: This is the first WES study of NF2-associated meningiomas. Besides second NF2 copy inactivation, we found low somatic burden in both tumors and high level of genomic instability in the atypical meningioma. Genomic instability resulting in altered gene

  5. Familial adult spinal muscular atrophy associated with the VAPB gene: report of 42 cases in Brazil

    Directory of Open Access Journals (Sweden)

    Victor Kosac

    2013-10-01

    Full Text Available Familial spinal muscular atrophy (FSMA associated with the vesicle-associated membrane protein-associated protein B (VAPB gene is a rare autosomal dominant disease with late onset and slow progression. We studied 10 of 42 patients from 5 families by taking clinical histories and performing physical exams, electrophysiological studies, and genetic tests. All patients presented late onset disease with slow progression characterized by fasciculations, proximal weakness, amyotrophy, and hypoactive deep tendon reflex, except two who exhibited brisk reflex. Two patients showed tongue fasciculations and respiratory insufficiency. Electrophysiological studies revealed patterns of lower motor neuron disease, and genetic testing identified a P56S mutation of the VAPB gene. Although it is a rare motor neuron disease, FSMA with this mutation might be much more prevalent in Brazil than expected, and many cases may be undiagnosed. Genetic exams should be performed whenever it is suspected in Brazil.

  6. The present use of soil and water in the basin of the creek Piçarrão-Araguari-MG-Brazil

    Directory of Open Access Journals (Sweden)

    Elizabete Oliveira Melo

    2010-09-01

    Full Text Available The agricultural expansion in the basin of the creek Piçarrão during the period from 1970 to 2005 produced changes in the use of soil and water that heretofore had not been documented. A diagnosis of the present situation was carried out to evaluate the prospect of agricultural activity in the basin. The literature was reviewed, 16 rural producers were interviewed, and the creek and its tributaries were inspected. The results of the study are presented in form of maps and tables. The total area drained by the creek is 388 km2, nine pivots do the agricultural irrigation, and the creek’s flow rate varies between 1.5 and 80.0 m3 per second with an annual average of 8.0 m3 per second. The study identified water availability as main limiting factor of agricultural development in the basin.

  7. To self produce black at brazil: a study of the didatic and pedagogical devices present in raça brasil magazine

    Directory of Open Access Journals (Sweden)

    Artur José Renda, Vitorino

    2014-04-01

    Full Text Available As from the teachings of Michel Foucault about self-government, it was made an analysis of the national magazine titled Raça Brasil , whose target audience is the black Brazilian with a view to show the didactic and pedagogical devices present in the magazine. To evaluate this discourse, it was analyzed a set of fifteen magazines which covered the period of January 2000 to May 2001 , where it was choose an edition for research through Foucaultian concepts , comparing the results with the bibliography. It indicated that the Raça Brasil magazine, from the devices dotted throughout the article, intends to model the Brazilian black identity, which has is common among its members the culture and memory called african-Brazilian, proposing thus, in the society, a taxonomy between blacks and whites. In short, was made an effort of the analysis about the discourse and commercials present in the highlighted number , pretending to understand what the magazine sees as "Black Brazilian" and what features, proposed in its discourse, about Brazilian black identity.

  8. Novel GAA mutations in patients with Pompe disease.

    Science.gov (United States)

    Turaça, Lauro Thiago; de Faria, Douglas Oliveira Soares; Kyosen, Sandra Obikawa; Teixeira, Valber Dias; Motta, Fabiana Louise; Pessoa, Juliana Gilbert; Rodrigues E Silva, Marina; de Almeida, Sandro Soares; D'Almeida, Vânia; Munoz Rojas, Maria Verônica; Martins, Ana Maria; Pesquero, João Bosco

    2015-04-25

    Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system intralysosomal accumulation of glycogen. Mutation identification in the GAA gene can be very important for early diagnosis, correlation between genotype-phenotype and therapeutic intervention. For this purpose, peripheral blood from 57 individuals susceptible to Pompe disease was collected and all exons of GAA gene were amplified; the sequences and the mutations were analyzed in silico to predict possible impact on the structure and function of the human protein. In this study, 46 individuals presented 33 alterations in the GAA gene sequence, among which five (c.547-67C>G, c.547-39T>G, p.R437H, p.L641V and p.L705P) have not been previously described in the literature. The alterations in the coding region included 15 missense mutations, three nonsense mutations and one deletion. One insertion and other 13 single base changes were found in the non-coding region. The mutation p.G611D was found in homozygosis in a one-year-old child, who presented low levels of GAA activity, hypotonia and hypertrophic cardiomyopathy. Two patients presented the new mutation p.L705P in association with c.-32-13T>G. They had low levels of GAA activity and developed late onset Pompe disease. In our study, we observed alterations in the GAA gene originating from Asians, African-Americans and Caucasians, highlighting the high heterogeneity of the Brazilian population. Considering that Pompe disease studies are not very common in Brazil, this study will help to better understand the potential pathogenic role of each change in the GAA gene. Furthermore, a precise and early molecular analysis improves genetic counseling besides allowing for a more efficient treatment in potential candidates. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Visceral leishmaniasis in Brazil

    Directory of Open Access Journals (Sweden)

    Mary Marcondes

    2013-10-01

    Full Text Available Visceral leishmaniasis (VL is among the most important vector-borne diseases that occur in Brazil, mainly due to its zoonotic nature. It is currently present in almost all Brazilian territory, and its control is a challenge both for veterinarians and for public health officials. The etiologic agent is Leishmania infantum (syn chagasi, and the main vector in Brazil is Lutzomyia longipalpis. Of all animals identified as reservoirs of VL, the dog is considered the most important domestic reservoir. Although the disease has already been identified in cats, the epidemiological role of this animal species is still unclear. This article presents a brief review of the epidemiological situation of the disease, its mode of transmission, clinical features in dogs and cats as well as possible risk factors associated with the occurrence of the disease in Brazil.

  10. Mutações predisponentes à trombofilia em indivíduos de Minas Gerais - Brasil com suspeita clínica de trombose Predisposing thrombophilic mutations in individuals with clinical suspicion of thrombosis from Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Sabrina P. Guimarães

    2009-02-01

    Full Text Available A trombose é reconhecidamente uma doença de caráter multifatorial. Sua ocorrência está intimamente relacionada à presença de fatores genéticos e adquiridos que concorrem isoladamente ou em associação para o seu desencadeamento. No entanto, a frequência dos fatores genéticos pode variar de acordo com a origem étnica e com outros aspectos epidemiológicos dos grupos de indivíduos e populações estudadas. No Brasil, dados referentes a indivíduos brasileiros e em especial do estado de Minas Gerais são escassos. O objetivo do presente estudo foi investigar a frequência das mutações fator V Leiden e G20210A no gene protrombina em 1.103 indivíduos com suspeita clínica de trombofilia, empregando a técnica da reação em cadeia da polimerase seguida de restrição enzimática (PCR-RFLP. Os dados foram analisados usando-se o programa Epi Info versão 6.04. A amostra consistiu de 76,16% mulheres e 23,84% homens, com média de idade de 43,06± 14,65. A mutação fator V Leiden foi observada em heterozigose em 7,52% dos indivíduos e em 0,36% em homozigose. A mutação G20210A no gene da protrombina apresentou-se em heterozigose em 5,90% dos indivíduos e em homozigose em 0,18%. O presente trabalho mostra a importância dos testes genéticos conforme o perfil da população analisada, ressaltando informações epidemiológicas da população brasileira e benefícios clínicos.Thrombosis is known to be a multifactorial disease. Its incidence is directly related to the presence of genetic and acquired factors that concur separately or in association to its appearance. However, the frequency of genetic factors can vary according to ethnic background and with other epidemiological aspects of populations. Data from Brazilian individuals and especially those from the State of Minas Gerais are scarce. The present study aims at investigating the frequencies of the factor v Leiden and the G20210G prothrombin gene mutations of 1103 individuals

  11. Genotype-Phenotype Correlations in CYP1B1-Associated Primary Congenital Glaucoma Patients Representing Two Large Cohorts from India and Brazil.

    Directory of Open Access Journals (Sweden)

    Mônica Barbosa de Melo

    Full Text Available Primary congenital glaucoma (PCG, occurs due to the developmental defects in the trabecular meshwork and anterior chamber angle in children. PCG exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated worldwide. Despite the diverse mutation spectra, the clinical implications of these mutations are yet unclear. The present study attempted to delineate the clinical profile of PCG in the background of CYP1B1 mutations from a large cohort of 901 subjects from India (n=601 and Brazil (n=300.Genotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301 and Brazil (n=150 to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters. The demographic (gender, and history of consanguinity and quantitative clinical (presenting intraocular pressure [IOP] and corneal diameter [CD] parameters were considered as binary and continuous variables, respectively, for PCG patients in the background of the overall mutation spectra and also with respect to the prevalent mutations in India (R368H and Brazil (4340delG. All these variables were fitted in a multivariate logistic regression model using the Akaike Information Criterion (AIC to estimate the adjusted odds ratio (OR using the R software (version 2.14.1.The overall mutation spectrum were similar across the Indian and Brazilian PCG cases, despite significantly higher number of homozygous mutations in the former (p=0.024 and compound heterozygous mutations in the later (p=0.012. A wide allelic heterogeneity was observed and only 6 mutations were infrequently shared between these two populations. The adjusted ORs for the binary (demographic and continuous (clinical variables did not indicate any susceptibility to the observed mutations (p>0.05.The present study demonstrated a lack of genotype-phenotype correlation of the demographic and clinical traits to CYP1B1 mutations in PCG at presentation. However, the

  12. Compostos funcionais presentes em bulbilhos de alhos armazenados sob refrigeração, provenientes de cultivos no Brasil e na China Functional compounds present in garlic cloves stored under refrigeration from crops in Brazil and China

    Directory of Open Access Journals (Sweden)

    Ester Yoshie Yosino da Silva

    2010-12-01

    Full Text Available O objetivo desta pesquisa foi determinar o teor de compostos funcionais presentes em bulbilhos de alho das cultivares 'Caçador' e 'Peruano', originárias do Brasil, e da cultivar 'Jinxiang', proveniente da China, durante o armazenamento pós-colheita até sessenta dias. O delineamento experimental utilizado foi o inteiramente casualizado, em esquema fatorial 3x5 (três cultivares de alho x 5 períodos de armazenagem, com três repetições, sendo a unidade experimental composta por 10 bulbos de alho. Os bulbos foram armazenados à temperatura de 22±1°C e umidade relativa de 70±2% e analisados quinzenalmente para teores de alicina, compostos fenólicos e atividade antioxidante pelo sistema -caroteno/ácido linoléio. De maneira geral, verificou-se que as propriedades funcionais das cultivares de alho estudadas foram alteradas durante o armazenamento. O perfil dos teores de alicina não foi alterado no período de armazenamento para a cultivar 'Caçador'. Entretanto, o perfil foi de degradação do bioativo aos 45 e 15 dias de armazenamento para as cultivares 'Peruano' e 'Jinxiang', respectivamente. O potencial antioxidante, medido pelo sistema -caroteno/ácido linoléico para as cultivares 'Caçador' e 'Jinxiang', foi superior em relação à cultivar 'Peruano', no início da avaliação. O perfil para todas as cultivares foi de redução do potencial, sendo que, a partir dos 30 dias de avaliação, deixou-se de observar essas diferenças. Quanto ao conteúdo de compostos fenólicos totais, observaram-se maiores teores para a cultivar 'Jinxiang' em relação às cultivares 'Caçador' e 'Peruano' no início da avaliação. Todas as cultivares apresentaram aumento significativo a partir dos 15 dias de avaliação. Portanto, as cultivares de alho avaliadas possuem atividade antioxidante, proveniente dos compostos organossulfurados e compostos fenólicos, a qual foi alterada com o armazenamento refrigerado.The objective of the present research

  13. Spotlight: Brazil.

    Science.gov (United States)

    Carter, M

    1996-08-01

    Brazil is South America's largest country and home to nearly half of the continent's people. Despite solid economic growth, Brazil has one of the world's widest income disparities. In the early 1990s, nearly 40% of urban and 66% of rural Brazilians lived in poverty. The streets of Brazil's cities are home to a large population of street children. Although it is difficult to estimate, 10 million children and youths may be either homeless or making a meager living off of the streets. Street children may be linked to prostitution and drugs and be the targets or perpetrators of violence. Child labor is an issue in Brazil. Today an estimated 30% of rural children and 9% of urban children ages 10-13 work in the formal economy. In some rural areas, 60% of workers are ages 5-17. Child labor also contributes to Brazil's relatively low educational attainment levels. UNICEF estimates that around 1990 only 1/3 of all Brazilian children continued on to secondary school, compared to 74% and 47%, respectively, for the Latin America and Caribbean regions. Immunization rates among Brazil's children are rising but still lag slightly behind regional averages. The mortality rate for children under age 5 decreased dramatically from 181 deaths for every 1000 live births in 1960 to 61/1000 in 1994. During the same time period, the average number of children born to a woman during her lifetime dropped from 6.2 to 2.8. This fertility decline is related in part to increased access to and acceptance of family planning. Contraceptive prevalence, including traditional and modern methods, is around 66%, with female sterilization and the pill being the most popular methods. Brazil's abortion rates are high, despite laws limiting access to abortion services. One estimate suggests that about 30% of all pregnancies are terminated through abortion each year.

  14. The thirty years of the petroleum impact and the Brazil; Os 30 anos do choque do petroleo e o Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Alveal, Carmen

    2007-07-01

    After the stormy thirty years that shacked the political, technical-productive and energetic sceneries, this chapter attempt to find which implications can be observed and which paper can be viewed for the Brazilian evolution on the world economy and energy scenery in the future. This brief reflexions explores the following hypothesis: in the recent decade, the Brazil insertion in the world scenery of productive mutations presents sub utilization of the growing position assumed by his petroleum industry.

  15. Analysis of technologies for natural gas transportation in Brazil: results comparison of the application of payback and NPV (Net Present Value) methods; Analise de tecnologias de transporte de gas natural no Brasil: comparacao dos resultados da aplicacao dos metodos 'payback' e VPL (Valor Presente Liquido)

    Energy Technology Data Exchange (ETDEWEB)

    Baioco, Juliana Souza; Santarem, Clarissa Andrade [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. de Engenharia de Petroleo; Bone, Rosemarie Broeker; Ferreira Filho, Virgilio Jose Martins [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. de Engenharia Industrial

    2008-07-01

    The increased demand for natural gas leads to global integration of markets, leading to decisions that cover the various technologies of transportation, noting the specific locations. The transport of natural gas considered more traditional (Liquefied Natural Gas and Pipeline) often unviable economically areas of operation due to cost. In this case, there are alternative technologies to reduce those costs. The article is to compare the technologies of transport, using the methodology of the Net Present Value (VPL) to identify one that has more positive VPL, which is the most profitable. Thus, in search of validate the results of SUBERO et al. (2004) for gas transport by Pipelines, Liquefied Natural Gas and Compressed Natural Gas. In addition, they are compared these results with the method of VPL and with the economic analysis presented in using the payback period of CHANG (2001) and SANTAREM et al. (2007). It was found that the results obtained in Brazil were identical to those obtained by CHANG (2001) and SUBERO et al. (2007), saving only some differences in magnitude due to the specific characteristics of the Brazilian economy. In other words, for the Brazilian case, the technology of Compressed Natural Gas (CNG) was the most economically viable with the method of VPL, followed by technology, Pipeline and Liquefied Natural Gas (LNG), regardless of the interest rates of 10% and 6.5% and periods of 20 and 30 years. The contribution of this work is to show that despite of the method, payback or VPL, the various alternatives for transporting natural gas to Brazil have the same ranking and economic viability. (author)

  16. ALS2 mutations

    Science.gov (United States)

    Schneider, Susanne A.; Carr, Lucinda; Deuschl, Guenther; Hopfner, Franziska; Stamelou, Maria; Wood, Nicholas W.; Bhatia, Kailash P.

    2014-01-01

    Objective: To determine the genetic etiology in 2 consanguineous families who presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral sclerosis associated with generalized dystonia. Methods: A combination of homozygosity mapping and whole-exome sequencing in the first family and Sanger sequencing of candidate genes in the second family were used. Results: Both families were found to have homozygous loss-of-function mutations in the amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene. Conclusions: We report generalized dystonia and cerebellar signs in association with ALS2-related disease. We suggest that the ALS2 gene should be screened for mutations in patients who present with a similar phenotype. PMID:24562058

  17. Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and Had a R642H/R642W Mutation in the SLC12A3 Gene

    Directory of Open Access Journals (Sweden)

    Shigeru Makino

    2014-01-01

    Full Text Available An 8-year-old Japanese boy presented with a generalized convulsion. He had hypokalemia (serum K 2.4 mEq/L, hypomagnesemia, and metabolic alkalosis (BE 5.7 mmol/L. In addition, his plasma renin activity was elevated. He was tentatively diagnosed with epilepsy on the basis of the electroencephalogram findings and was treated by potassium L-aspartate and carbamazepine to control the hypokalemia and seizure, respectively. However, a year later, the patient continued to have similar abnormal laboratory data. A presumptive diagnosis of Gitelman syndrome (GS was then made and the patient’s peripheral blood mononuclear cells were subjected to sequence analysis of the SLC12A3 gene, which encodes a thiazide-sensitive sodium-chloride cotransporter. The patient was found to have compound heterozygous mutations, namely, R642H inherited from his father and R642W inherited from his mother. Thus, if a patient shows persistent hypokalemia and metabolic alkalosis, GS must be considered, even if the patient exhibits atypical clinical symptoms.

  18. A homozygote for the c.459+1G>A mutation in the ARSA gene presents with cerebellar ataxia as the only first clinical sign of metachromatic leukodystrophy.

    Science.gov (United States)

    Lugowska, Agnieszka; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Szczepanik, Elżbieta; Goszczańska-Ciuchta, Alicja; Bednarska-Makaruk, Małgorzata

    2014-03-15

    Metachromatic leukodystrophy (MLD) is a rare lysosomal disorder caused by deficient activity of arylsulfatase A or the lack of saposin B, which results in the accumulation of sulfatide in the oligodendrocytes and in the Schwann cells. Three main clinical types of MLD can be distinguished according to the age of onset and the dynamics of clinical outcome: late infantile, juvenile, and adult. We report on a case of late infantile MLD presenting with cerebellar ataxia as the only first clinical sign preceding even changes in white matter visible in MR imaging. The diagnosis was made on the basis of successive MRI, characteristic of demyelination, which developed in the course of the disease, and on the results of the following biochemical and molecular analyses. Very low residual activity of arylsulfatase A was demonstrated in blood leukocytes and the patient was a homozygote for a common mutation c.459+1G>A in the ARSA gene. Since cerebellar ataxia is a relatively common but unspecific neurological symptom in toddlers, it is recommended that MLD be considered as part of the differential diagnosis even if the initial neuroimaging studies are normal and ataxia is the only clinical symptom of the disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

    Directory of Open Access Journals (Sweden)

    Grazia Bossi

    2017-10-01

    Full Text Available We report definitive diagnosis and effective treatment with oral cholic acid in one Italian male child affected by 3β- hydroxy-Δ5-C27-steroid dehydrogenase (3β- HSD deficiency. He presented with failure to thrive, hepatomegaly and multiple cystic images in kidneys; no biochemical evidence of cholestasis. Large amounts of bile acid metabolites was detected in urine by fast atom bombardment ionization mass spectrometry (FAB-MS. HSDH3B7 gene analysis identified one mutation in intron 4, at nucleotide 432, G>A substitution that has never been reported before.The replacement therapy with oral cholic acid started early after the diagnosis and is still ongoing. Three years later hepatomegaly is no longer evident, liver function is normal and the child is growing regularly. In our experience, clinical features of 3β-HSD deficiency can be very poor and even cholestasis can lack at diagnosis. Early replacement therapy with cholic acid is safe and leads to clinical and biochemical control of the disease.

  20. Mutation in Aldosterone Producing Adenoma

    Directory of Open Access Journals (Sweden)

    Jian-Jhong Wang

    2017-09-01

    Full Text Available Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1 mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.

  1. Mitochondrial mutations in cancer

    National Research Council Canada - National Science Library

    Brandon, M; Baldi, P; Wallace, D C

    2006-01-01

    ...). The mitochondria are assembled from both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) genes. The mtDNA codes for 37 genes essential of OXPHOS, is present in thousands of copies per cell, and has a very high mutations rate...

  2. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  3. Equine influenza in Brazil

    Directory of Open Access Journals (Sweden)

    Patricia Filippsen Favaro

    2016-06-01

    Full Text Available Equine influenza virus (EIV (H3N8 and H7N7 is the causative agent of equine influenza, or equine flu. The H7N7 subtype has been considered to be extinct worldwide since 1980. Affected animals have respiratory symptoms that can be worsened by secondary bacterial respiratory infection, thereby leading to great economic losses in the horse-breeding industry. In Brazil, equine influenza outbreaks were first reported in 1963 and studies on hemagglutination antibodies against viral subtypes in Brazilian horses have been conducted since then. The objective of the present review was to present the history of the emergence of EIV around the world and in Brazil and the studies that have thus far been developed on EIV in Brazilian equines.

  4. Giant thrombosed intracavernous carotid artery aneurysm presenting as Tolosa–Hunt syndrome in a patient harboring a new pathogenic neurofibromatosis type 1 mutation: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Conforti R

    2014-01-01

    Full Text Available Renata Conforti,1 Mario Cirillo,2 Valeria Marrone,1 Rosario Galasso,1 Guglielmo Capaldo,3 Teresa Giugliano,4 Assunta Scuotto,1 Giulio Piluso,4 Mariarosa AB Melone3,51Neuroradiology Unit, Department of Clinical and Experimental Medicine and Surgery, 2Radiology Unit, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, 3Division of Neurology, Department of Clinical and Experimental Medicine and Surgery, 4Department of Biochemistry, Biophysics and General Pathology, School of Medicine, Second University of Naples, Naples, Italy; 5Institute of Protein Biochemistry, National Research Council, Naples, ItalyAbstract: Neurofibromatosis type 1 (NF1 is a relatively common single-gene disorder, and is caused by heterozygous mutations in the NF1 gene that result in a loss of activity or in a nonfunctional neurofibromin protein. Despite the common association of NF1 with neurocutaneous features, its pathology can extend to numerous tissues not derived from the neural crest. Among the rare cerebrovascular abnormalities in NF1, more than 85% of cases are of purely occlusive or stenotic nature, with intracranial aneurysm being uncommon. Predominantly, the aneurysms are located in the internal carotid arteries (ICAs, being very rare bilateral aneurysms. This report describes a very unusual case of fusiform aneurysms of both ICAs in a Caucasian NF1 patient, with a new pathogenic intragenic heterozygous deletion of the NF1 gene, presenting at age 22 years with Tolosa–Hunt syndrome, because of partial thrombosis of the left giant intracavernous aneurysm. Medical treatment with anticoagulant therapy allowed a good outcome for the patient. In conclusion, early identification of cerebral arteriopathy in NF1 and close follow-up of its progression by neuroimaging may lead to early medical or surgical intervention and prevention of significant neurologic complications.Keywords: neurofibromatosis type 1, NF1 gene, multiplex ligation

  5. Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6.

    Science.gov (United States)

    Ferreira, Isabel D; Martinelli, Axel; Rodrigues, Louise A; do Carmo, Ediclei L; do Rosário, Virgílio E; Póvoa, Marinete M; Cravo, Pedro

    2008-02-01

    To evaluate the in vitro efficacy of artesunate (ATN) and artemether (ATH) against Plasmodium falciparum isolates from the Brazilian Amazon state of Pará and to search for mutations and/or altered copy numbers in the putative resistance-associated pfcrt, pfmdr1 and pfATPase6 genes. In vitro efficacy of ATN and ATH was successfully measured in 56 freshly collected P. falciparum isolates, using a conventional WHO microtest with minor modifications. Single nucleotide polymorphisms (SNPs) in the same isolates were inspected using DNA sequencing and/or PCR-RFLP. We used real-time quantitative PCR to assess gene copy numbers. ATN and ATH geometric mean IC(50)s were 0.85 nm, 95% CI (0.55-1.15) and 3.0 nm, 95% CI (1.5-4.5), respectively. There was extremely limited diversity of pfcrt and pfmdr1 genotypes and three SNPs were identified in the pfATPase6 gene: one T to A synonymous mutation at nucleotide 2694 and two non-synonymous (both G to A) mutations at nucleotides 110 and 1916, causing predicted aminoacid shifts of arginine to lysine and of glycine to aspartate, respectively. The previously reported S769N mutation was not detected in any of the isolates inspected. In addition, no gene amplifications were detected in a subset of eight isolates. Artemisinin derivatives display satisfactory in vitro activity locally and the pfATPase6 gene is distinct from that reported in French Guiana, suggesting that those haplotypes have not been introduced regionally.

  6. Prevalent mutations in fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Gregersen, N; Andresen, B S; Bross, P

    2000-01-01

    UNLABELLED: The mutational spectrum in a given disease-associated gene is often comprised of a large number of different mutations, of which a single or a few are present in a large proportion of diseased individuals. Such prevalent mutations are known in four genes of the fatty acid oxidation...... carrying the prevalent 985A > G mutation are at risk of developing life-threatening attacks. In SCAD/ethylmalonic aciduria, on the other hand, the presence of the prevalent susceptibility variations, 625A and 511T, in the SCAD gene seems to require additional genetic and cellular factors to be present...... in order to result in a phenotype. For the prevalent mutations in the LCHAD and CPT II genes further data are needed to evaluate the penetrance and risk of manifest disease when carrying these mutations. CONCLUSION: Assessment of the prevalence of a prevalent mutation in the mutation spectrum...

  7. BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC probands from Southern Brazil: Are international testing criteria appropriate for this specific population?

    Directory of Open Access Journals (Sweden)

    Bárbara Alemar

    Full Text Available Germline pathogenic variants in BRCA1 and BRCA2 (BRCA are the main cause of Hereditary Breast and Ovarian Cancer syndrome (HBOC.In this study we evaluated the mutational profile and prevalence of BRCA pathogenic/likely pathogenic variants among probands fulfilling the NCCN HBOC testing criteria. We characterized the clinical profile of these individuals and explored the performance of international testing criteria.A pathogenic/likely pathogenic variant was detected in 19.1% of 418 probands, including seven novel frameshift variants. Variants of uncertain significance were found in 5.7% of individuals. We evaluated 50 testing criteria and mutation probability algorithms. There was a significant odds-ratio (OR for mutation prediction (p ≤ 0.05 for 25 criteria; 14 of these had p ≤ 0.001. Using a cutoff point of four criteria, the sensitivity is 83.8%, and the specificity is 53.5% for being a carrier. The prevalence of pathogenic/likely pathogenic variants for each criterion ranged from 22.1% to 55.6%, and criteria with the highest ORs were those related to triple-negative breast cancer or ovarian cancer.This is the largest study of comprehensive BRCA testing among Brazilians to date, and the first to analyze clinical criteria for genetic testing. Several criteria that are not included in the NCCN achieved a higher predictive value. Identification of the most informative criteria for each population will assist in the development of a rational approach to genetic testing, and will enable the prioritization of high-risk individuals as a first step towards offering testing in low-income countries.

  8. Work and Productive Restructuring in Neoliberal Brazil – Precariousness of Work and Salary Redundancy

    Directory of Open Access Journals (Sweden)

    Giovanni Alves

    2009-01-01

    Full Text Available The purpose of this article is to analyze the social mutations that occur in the world of labor based on the neoliberal era in Brazil. It examines the precariousness of work as being an element that composes the new social metabolism that emerges with the productive restructuring of capital and the constitution of the neoliberal State. It presents as the objective causes of the increased precariousness of work the intensification and expansion of the exploitation and plundering of the labor force, the dismounting of labor collectives and of corporate-union resistance; as well as the social fragmentation in the cities due to the exacerbated growth of mass unemployment.

  9. Determination of the equivalent doses due to the ingestion of radionuclides from the uranium and thorium series presents in drinking waters of the region of Santa Luzia, Paraiba state, Brazil; Determinacao das doses equivalentes devido a ingestao de radionuclideos das series do uranio e torio presentes em aguas de consumo do municipio de Santa Luzia, estado da Paraiba

    Energy Technology Data Exchange (ETDEWEB)

    Pastura, Valeria F. da S., E-mail: vpastura@cnen.gov.b [Comissao Nacional de Energia Nuclear (DRSN/CNEN), Rio de Janeiro, RJ (Brazil). Diretoria de Radioprotecao e Seguranca Nuclear. Coordenacao de Materias Primas e Minerais; Campos, Thomas F. da C.; Petta, Reinaldo A., E-mail: thomascampos@geologia.ufrn.b, E-mail: petta@geologia.ufrn.b [Universidade Federal do Rio Grande do Norte (LARANA/UFRN), Natal, RN (Brazil). Lab. de Radioatividade Natural

    2011-10-26

    This paper determined the original dose equivalents from radionuclides of uranium and thorium series in a drinking water of well which is supplied to the population of Santa Luzia, Paraiba state, Brazil. The collected waters are near to the mineralized phlegmatic bodies in rose quartz and amazonite feldspar. Radiometric measurements performed on the feldspar vein point out counting ratios surrounding 30000 cps and the analysis of collected samples of minerals presented tenors for the {sup 226}Ra and {sup 219}Pb varying from 0.50 to 2.30 Bq/sw. For determination of concentration of radionuclides U{sub Total}, {sup 226}Ra, {sup 228}Ra and {sup 219}Pb, found in the not desalinated, two methods were used, spectrophotometry with arsenazo and radiochemistry, both realized in the CNEN-LAPOC laboratories. For the calculation of dose equivalent it was taken into consideration the following parameters: the dose coefficients for incorporation by ingestion for public individuals with ages over 17 years (Norma CNEN-NN-3.01, Regulatory Position 3.01/011) and daily ingestion of 4 liters of water, which is over the recommended by the WHO of 2L/day - 1993. The obtained values were compared with the reference value for compromised dose equivalent established by WHO for evaluate the risk potential to the health of population, by ingestion. The radionuclide concentrations in the wells varies from 0.054 to 0.21 Bq/L, resulting dose equivalents of 3.94 x 10{sup -3} mSv/year and 0.17 mSv/year in the studied population

  10. Monoallelic mutation analysis (MAMA) for identifying germline mutations.

    Science.gov (United States)

    Papadopoulos, N; Leach, F S; Kinzler, K W; Vogelstein, B

    1995-09-01

    Dissection of germline mutations in a sensitive and specific manner presents a continuing challenge. In dominantly inherited diseases, mutations occur in only one allele and are often masked by the normal allele. Here we report the development of a sensitive and specific diagnostic strategy based on somatic cell hybridization termed MAMA (monoallelic mutation analysis). We have demonstrated the utility of this strategy in two different hereditary colorectal cancer syndromes, one caused by a defective tumour suppressor gene on chromosome 5 (familial adenomatous polyposis, FAP) and the other caused by a defective mismatch repair gene on chromosome 2 (hereditary non-polyposis colorectal cancer, HNPCC).

  11. Brazil Low Carbon Case Study : Waste

    OpenAIRE

    World Bank

    2010-01-01

    This report synthesis the findings for the waste sector of a broader study, the Brazil low carbon study, which was undertaken by the World Bank in its initiative to support Brazil's integrated effort towards reducing national and global emissions of Greenhouse Gases (GHG) while promoting long term development. The purpose of the present report is to assist in the preparation of public poli...

  12. A novel p. Gly630Ser mutation of COL2A1 in a Chinese family with presentations of Legg-Calve-Perthes disease or avascular necrosis of the femoral head.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available OBJECTIVE: Mutations in the type II collagen gene are associated with certain human disorders, collectively termed type II collagenopathies. They include Legg-Calvé-Perthes disease (LCPD and avascular necrosis of the femoral head (ANFH. These two diseases are skeletal dysplasias, inherited in an autosomal dominant fashion, characterized by groin pain, dislocation of the hip and diminished joint mobility. Coxa vara and elevation of the greater trochanter of the femur comprise the typical phenotype of LCPD, but do not occur in ANFH. Lack of synthesis of type II collagen and structural defects are responsible for the major clinical outcomes, because collagen is the essential matrix protein of all connective tissues. Type II collagen, encoded by the COL2A1 gene, contains N- and C- terminal regions that are cleaved after secretion into the extracellular matrix, and the core area is composed of a triple helical (Gly-X-Y domain. If the Gly in this specific region is replaced by other amino acids, the structure of type II collagen will be destroyed. METHOD: Forty-five members of a four-generation family were recruited and investigated. Diagnosis was made by independent orthopedic surgeons and radiologists. A mutation of the COL2A1 gene was detected. RESULT: In our research, we identify a heterozygous mutation (c.1888 G>A, p. Gly630Ser in exon 29 of COL2A1 in the Gly-X-Y domain, in a Chinese family affected by LCPD and ANFH. Our findings provide significant clues to the phenotype-genotype relationships in these syndromes and may be helpful in clinical diagnosis. Furthermore, these results should assist further studies of the mechanisms underlying collagen diseases. CONCLUSION: Our data add new variants to the repertoire of COL2A1 mutation resulting in related collagenopathies.

  13. Mutation analysis of Swedish haemophilia B families - high frequency of unique mutations.

    Science.gov (United States)

    Mårtensson, A; Letelier, A; Halldén, C; Ljung, R

    2016-05-01

    Haemophilia B is caused by a heterogeneous spectrum of mutations. Mutation characterization is important in genetic counselling, prenatal diagnosis and to predict risk of inhibitor development. To study the mutation spectrum, frequency of unique recurrent mutations, genotype-phenotype association and inhibitor development in a population-based study of the complete Swedish haemophilia B population. The study included, facilitated by centralized DNA diagnostics, the complete registered Swedish haemophilia B population (113 families: 47 severe, 22 moderate and 44 mild), each represented by a single patient. Mutation characterization was performed by conventional sequencing of all exons and haplotyping by genotyping of single nucleotide variants and microsatellites. A mutation was found in every family: eight had large deletions, three had small deletions (mutations were found and were predicted to be deleterious. Sixteen mutations (one total gene deletion, 14 substitutions and one acceptor splice site) were present in more than one family. Of the single nucleotide mutations (37/102), 36% arose at CpG sites. Haplotyping of families with identical mutations and present analyses showed that the frequency of unique mutations was at least 65%. Inhibitors developed in 9/47 (19%) patients with severe haemophilia B. The spectrum of haemophilia B mutations reveals at least 65% of the families carry a unique mutation, but with more inhibitor patients than reported internationally, probably as a result of many 'null' mutations. © 2015 John Wiley & Sons Ltd.

  14. Oral health policies in Brazil

    Directory of Open Access Journals (Sweden)

    Gilberto Alfredo Pucca Junior

    2009-06-01

    Full Text Available Since Oral Health policies in Brazil have been constructed according to circumstances and possibilities, they should be understood within a given context. The present analysis contextualizes several issues of the Brazilian Oral Health Policy, called "Smiling Brazil", and describes its present stage of development. Today it involves re-organizing basic oral health care by deploying Oral Health Teams within the Family Health strategy, setting up Centers of Dental Specialists within an Oral Health network as a secondary care measure, setting up Regional Laboratories of Dental Prosthesis and a more extensive fluoridation of the public water supply.

  15. Characterization of the geochemical processes present in the radionuclides and metals mobilization in the tailing dam at the Uranium Mining and Milling Facilities - Pocos de Caldas, MG, Brazil; Caracterizacao dos processos geoquimicos atuantes na mobilizacao de radionuclideos e metais na bacia de rejeitos do complexo minero-industrial de Pocos de Caldas, MG, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Patricia Freitas

    1995-08-01

    In Brazil, the first step of nuclear fuel cycle - the mining and milling of the uranium ore - is developed at the Uranium Mining and Milling Facilities of Pocos de Caldas, Minas Gerais state. The wastes management is a very important aspect of the process. The understanding of the geochemical processes that occur in the tailings dam is a key question to define a plan of action concerning the decommissioning strategy of the facility. The objective of the present work was to give some issues to help in the adoption of the remedial actions concerning the decommissioning of the facility. It focused on the characterization of the most important geochemical processes regulating the mobilization of radionuclides and heavy metals in the tailings dam. Two cores from the tailings dam (uncovered area) were collected. Seepage and drainage waters were sampled, the same being true for the tailings dam lake. Groundwater form an aquifer bellow the tailings dam and superficial waters from a river that receives the effluents of the dam (Soberbo River) were also sampled. Data from the mining company were used to calculate the inventory of radionuclides and heavy metals deposited in the waste dam.The obtained results showed that pyrite oxidation is the key process in the mobilization of radionuclides and heavy metals from the wastes. Pyrite oxidation is a process regulated by oxygen diffusion and water. In the studied scenario it could be shown that the process was limited to a one meter deep layer in the uncovered part of the waste dam. Because of this, Fe, Al, Mn, Zn, Th and {sup 238} U showed higher concentrations in the bottom layers of the cores in relation to the upper ones. {sup 226} Ra and {sup 210} Pb showed opposite patterns. The coprecipitation with Ca SO{sub 4} was the most relevant mechanism in both radionuclides immobilization in the wastes. Sulfate was the only chemical species that could be assigned as a contaminant in aquifer bellow the waste dam. As a conclusion, the

  16. Mutations causative of familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Benn, Marianne; Watts, Gerald F; Tybjærg-Hansen, Anne

    2016-01-01

    AIMS: Ideally, familial hypercholesterolaemia (FH) is diagnosed by testing for mutations that decrease the catabolism of low-density lipoprotein (LDL) cholesterol; however, genetic testing is not universally available. The aim of the present study was to assess the frequency and predictors of FH...... causing mutations in 98 098 participants from the general population, the Copenhagen General Population Study. METHODS AND RESULTS: We genotyped for LDLR[W23X;W66G;W556S] and APOB[R3500Q] accounting for 38.7% of pathogenic FH mutations in Copenhagen. Clinical FH assessment excluded mutation information....... The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH...

  17. Islam in Brazil or the Islam of Brazil?

    Directory of Open Access Journals (Sweden)

    Vitória Peres de Oliveira

    Full Text Available This article is about the Islam lived and practiced by Muslim communities in Brazil. It attempts to understand the identity that this religion is acquiring in the Brazilian religious field. It discusses the discrepancy between figures presented by the official census and Muslim sources and offers models to think about the emergence of Muslim communities and possible changes due to the entrance of "new Muslims" (converted Brazilians without Muslim origin. Based on empirical data, it discusses the difficulties found and strategies used by the communities. It suggests that Islam in Brazil is starting to put down roots and to have a profile of its own.

  18. Impacts of mutation effects and population size on mutation rate in asexual populations: a simulation study

    Directory of Open Access Journals (Sweden)

    Huang Zhuoran

    2010-09-01

    Full Text Available Abstract Background In any natural population, mutation is the primary source of genetic variation required for evolutionary novelty and adaptation. Nevertheless, most mutations, especially those with phenotypic effects, are harmful and are consequently removed by natural selection. For this reason, under natural selection, an organism will evolve to a lower mutation rate. Overall, the action of natural selection on mutation rate is related to population size and mutation effects. Although theoretical work has intensively investigated the relationship between natural selection and mutation rate, most of these studies have focused on individual competition within a population, rather than on competition among populations. The aim of the present study was to use computer simulations to investigate how natural selection adjusts mutation rate among asexually reproducing subpopulations with different mutation rates. Results The competition results for the different subpopulations showed that a population could evolve to an "optimum" mutation rate during long-term evolution, and that this rate was modulated by both population size and mutation effects. A larger population could evolve to a higher optimum mutation rate than could a smaller population. The optimum mutation rate depended on both the fraction and the effects of beneficial mutations, rather than on the effects of deleterious ones. The optimum mutation rate increased with either the fraction or the effects of beneficial mutations. When strongly favored mutations appeared, the optimum mutation rate was elevated to a much higher level. The competition time among the subpopulations also substantially shortened. Conclusions Competition at the population level revealed that the evolution of the mutation rate in asexual populations was determined by both population size and mutation effects. The most striking finding was that beneficial mutations, rather than deleterious mutations, were the

  19. All about neosporosis in Brazil.

    Science.gov (United States)

    Cerqueira-Cézar, Camila Koutsodontis; Calero-Bernal, Rafael; Dubey, Jitender Prakash; Gennari, Solange Maria

    2017-01-01

    Neospora caninum is protozoan parasite with domestic and wild dogs, coyotes and grey wolves as the definitive hosts and many warm-blooded animals as intermediate hosts. It was cultivated and named in 1988. Neosporosis is a major disease of cattle and has no public health significance. Since 1990's N. caninum has emerged as a major cause of abortion in cattle worldwide, including in Brazil. N. caninum also causes clinical infections in several other animal species. Considerable progress has been made in understanding the biology of N. caninum and there are more than 200 papers on this subject from Brazil. However, most of the reports on neosporosis from Brazil are serological surveys. Overall, little is known of clinical neosporosis in Brazil, particularly cattle. The few reports pertain to sporadic cases of abortion with no information on epidemics or storms of abortion. The objective of the present review is to summarize all reports from Brazil and suggest topic for further research, including prevalence of N. caninum oocysts in soil or in canine feces, and determining if there are additional definitive hosts, other than the domestic dog. There is need for a national survey in cattle using defined parameters. Future researches should focus on molecular characterization of N. caninum strains, possibility of vaccine production and relationship between wildlife and livestock epidemiology.

  20. All about neosporosis in Brazil

    Directory of Open Access Journals (Sweden)

    Camila Koutsodontis Cerqueira-Cézar

    2017-08-01

    Full Text Available Abstract Neospora caninum is protozoan parasite with domestic and wild dogs, coyotes and grey wolves as the definitive hosts and many warm-blooded animals as intermediate hosts. It was cultivated and named in 1988. Neosporosis is a major disease of cattle and has no public health significance. Since 1990’s N. caninum has emerged as a major cause of abortion in cattle worldwide, including in Brazil. N. caninum also causes clinical infections in several other animal species. Considerable progress has been made in understanding the biology of N. caninum and there are more than 200 papers on this subject from Brazil. However, most of the reports on neosporosis from Brazil are serological surveys. Overall, little is known of clinical neosporosis in Brazil, particularly cattle. The few reports pertain to sporadic cases of abortion with no information on epidemics or storms of abortion. The objective of the present review is to summarize all reports from Brazil and suggest topic for further research, including prevalence of N. caninum oocysts in soil or in canine feces, and determining if there are additional definitive hosts, other than the domestic dog. There is need for a national survey in cattle using defined parameters. Future researches should focus on molecular characterization of N. caninum strains, possibility of vaccine production and relationship between wildlife and livestock epidemiology.

  1. HNPCC: Six new pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Epplen Joerg T

    2004-06-01

    Full Text Available Abstract Background Hereditary non-polyposis colorectal cancer (HNPCC is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR. HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in the DNA mismatch-repair genes MLH1, MSH2 and MSH6. Methods Patients with clinical diagnosis of HNPCC were counselled. Tumor specimen were analysed for microsatellite instability and immunohistochemistry for MLH1, MSH2 and MSH6 protein was performed. If one of these proteins was not detectable in the tumor mutation analysis of the corresponding gene was carried out. Results We identified 6 frameshift mutations (2 in MLH1, 3 in MSH2, 1 in MSH6 resulting in a premature stop: two mutations in MLH1 (c.2198_2199insAACA [p.N733fsX745], c.2076_2077delTG [p.G693fsX702], three mutations in MSH2 (c.810_811delGT [p.C271fsX282], c.763_766delAGTGinsTT [p.F255fsX282], c.873_876delGACT [p.L292fsX298] and one mutation in MSH6 (c.1421_1422dupTG [p.C475fsX480]. All six tumors tested for microsatellite instability showed high levels of microsatellite instability (MSI-H. Conclusions HNPCC in families with MSH6 germline mutations may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations.

  2. IDRC in Brazil

    International Development Research Centre (IDRC) Digital Library (Canada)

    that help the government promote creativity and entrepreneurship. □ Wage inequalities in Brazil and India. Funding: $247,200. Duration: 2013–2015. Grantee: Centro Brasileiro de Analise e Planejamento, Brazil. Although poverty in Brazil and India has diminished, inequality among wage earners remains high. Think tanks ...

  3. Infantile Hemophagocytic Lymphohistiocytosis in a Case of Chediak-Higashi Syndrome Caused by a Mutation in the LYST/CHS1 Gene Presenting With Delayed Umbilical Cord Detachment and Diarrhea

    DEFF Research Database (Denmark)

    Nielsen, Christian; Agergaard, Charlotte N; Jakobsen, Marianne A

    2015-01-01

    perforin content in CD8 T cells seems to correlate to the immune activation state of the patient with 82% and 8% perforin-containing CD8 T cells at active and nonactive hemophagocytic lymphohistiocytosis (HLH) disease, respectively. HLH was confirmed by hemophagocytosis in bone marrow and absent natural...... killer cell activity. The patient carried a homozygous G>A mutation in the 3' splice site of intron 24 of the LYST/CHS1 gene, leading to the use of an alternative YAG splice site located in exon 25, introducing a premature STOP codon (L2355fsX2370; NP_000072.2). The early-onset accelerated phase...... in this severe phenotype of Chediak-Higashi syndrome was probably induced by rotaviral infection. Interestingly, the intracellular perforin content in CD8 T cells seems to correlate to the immune activation state of the patient. Late separation of the umbilical cord in concordance with clinical symptoms should...

  4. Manaus, Brazil

    Science.gov (United States)

    2002-01-01

    The junctions of the Amazon and the Rio Negro Rivers at Manaus, Brazil. The Rio Negro flows 2300 km from Columbia, and is the dark current forming the north side of the river. It gets its color from the high tannin content in the water. The Amazon is sediment laden, appearing brown in this simulated natural color image. Manaus is the capital of Amazonas state, and has a population in excess of one million. The ASTER image covers an area of 60 x 45 km. This image was acquired on July 16, 2000 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image Earth for the next 6 years to map and monitor the changing surface of our planet.ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. Dr. Anne Kahle at NASA's Jet Propulsion Laboratory, Pasadena, California, is the U.S. Science team leader; Bjorn Eng of JPL is the project manager. The Terra mission is part of NASA's Earth Science Enterprise, a long-term research and technology program designed to examine Earth's land, oceans, atmosphere, ice and life as a total integrated system.The broad spectral coverage and high spectral resolution of ASTER will provide scientists in numerous disciplines with critical information for surface mapping, and monitoring dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface

  5. Molecular Characterization of Pediatric Acute Myeloid Leukemia: Results of a Multicentric Study in Brazil.

    Science.gov (United States)

    Andrade, Francianne Gomes; Noronha, Elda Pereira; Brisson, Gisele Dallapicola; Dos Santos Vicente Bueno, Filipe; Cezar, Ingrid Sardou; Terra-Granado, Eugênia; Thuler, Luiz Claudio Santos; Pombo-de-Oliveira, Maria S

    2016-11-01

    The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil. Seven hundred and three de novo pediatric AML cases (2000-2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of FLT3, NRAS, KRAS, PTPN11, and c-KIT genes were analyzed as well as fusion genes (RUNX1-RUNX1T1, MLL/KMT2A-r, CBFβ-MYH11, and PML-RARα) associated with AML. Patients were treated out of the clinical trial although following the BFM-AML2004 protocol. Acute promyelocytic leukemia (APL) was treated differently. AML with Down syndrome was excluded. There were significant differences in gene mutations among age ranges (≤2 years-old; >2-10 years old and ≥11 years old) and the nonrandom association between type I/II mutations. Lower white blood cell count (≤50 × 109/L) was associated with RUNX1-RUNX1T1, whereas higher WBC with CBFβ-MYH11 (p <0.05). Cumulative pOS in 5 years was 37.7 ± 2.8% for total AMLs and 59.8 ± 6.2% for APL (p = 0.03). pOS differences were observed between Brazilian regions. The South-Southeast regions had a better 5-year pOS, whereas the Midwest region presented the poorest pOS (23.7 ± 4.9%). PTPN11 mutations conferred an adverse prognosis as an independent prognostic factor. Identification of genetic subgroups contributes to the molecular epidemiology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  6. Why do patients undergoing anterior cruciate ligament reconstruction in Brazil stay in hospital for longer periods than in other countries? Prospective evaluation of 30 patients and presentation of possible discharge criteria

    Directory of Open Access Journals (Sweden)

    Diego Costa Astur

    2013-08-01

    Full Text Available OBJECTIVE: Evaluate a better moment by the medical team and patient to be discharged and relate to possible medical discharge criteria. METHODS: 31 anterior cruciate ligament reconstructed patients under similar conditions prospectively evaluated about the possibility of discharge with 24 and 48 hours after surgery and possibles discharges criteria such as pain, range of motion and capacity quadriceps contraction, besides the use of a validated scale to measure the patient's functional independence. RESULTS: 50% and 6.4% of patients prefer remain hospitalized after 24 and 48 hours of surgery, respectively. The average of the visual analogue scale of pain was 2.63 and 1.76 points, and the range of motion of 79º and 86,7º after 24 and 48 hours, respectively. 100% of patients were able to quadriceps contraction in every evaluated moments. CONCLUSION: In Brazil, possible discharged criteria as pain, range of motion, quad contraction and motor independence motor function scale show that anterior cruciate reconstruction reconstructed patients could be discharged after 24 hours of surgery. However, 50% of patients still prefer to remain hospitalized for longer periods.

  7. 21-Hydroxylase deficiency in Brazil

    Directory of Open Access Journals (Sweden)

    T.A.S.S. Bachega

    2000-10-01

    Full Text Available We determined the frequency of large rearrangements and point mutations in 130 Brazilian patients with 21-hydroxylase deficiency and correlated genotype with phenotype. The frequency of CYP21 deletions was lower (4.4% than in most of the previous series described, whereas the frequency of large gene conversions was similar to the frequency reported in the literature (6.6%. The most frequent point mutations were I2 splice (41.8% in salt wasting - SW, I172N (32.6% in simple virilizing - SV and V281L (40.2% in the late onset form - LO. The frequency of the nine most common point mutations was similar to that reported for other countries. The 93 fully genotyped patients were classified into 3 mutation groups based on the degree of enzymatic activity (A@ 2%, C>20%. In group A, 62% of cases presented the SW form; in group B, 96% the SV form, and in group C, 88% the LO form. We diagnosed 80% of the affected alleles after screening for large rearrangements and 15 point mutations. To diagnose these remaining alleles we sequenced the CYP21 gene of one patient with the SV form and identified a heterozygous G->A transition in codon 424. This mutation leads to a substitution of glycine by serine in a conserved region and was also found in a compound heterozygous state in 4 other patients. The mutation G424S presented a linkage disequilibrium with CYP21P and C4A gene deletions and HLA DR17, suggesting a probable founder effect. Search for the G424S mutation in other populations will reveal if it is restricted to the Brazilian patients or if it has a wider ethnic distribution.

  8. A new mutation in blau syndrome.

    Science.gov (United States)

    Zeybek, Cengiz; Basbozkurt, Gokalp; Gul, Davut; Demirkaya, Erkan; Gok, Faysal

    2015-01-01

    Blau syndrome is a rare, autosomal dominant, granulomatous autoinflammatory disease. The classic triad of the disease includes recurrent uveitis, granulomatous dermatitis, and symmetrical arthritis. Blau syndrome is related to mutations located at the 16q12.2-13 gene locus. To date, 11 NOD2 gene mutations causing Blau syndrome have been described. Here, we describe a 5-year-old male patient who presented with Blau syndrome associated with a novel sporadic gene mutation that has not been reported previously.

  9. APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations.

    Science.gov (United States)

    Andresen, Per Arne; Heimdal, Ketil; Aaberg, Kristin; Eklo, Katrine; Eklo, Kristin; Ariansen, Sarah; Silye, Alexandra; Fausa, Olav; Aabakken, Lars; Aretz, Stefan; Eide, Tor J; Gedde-Dahl, Tobias

    2009-10-01

    Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease caused by mutations in the adenomatous polyposis coli (APC) gene. Massive formation of colorectal adenomas, of which some will inevitably develop into adenocarcinomas, is the hallmark of the disease. Characterization of causative APC mutations allows presymptomatic diagnosis, close follow-up and prophylactic intervention in families. To date more than 900 different germline mutations have been characterized worldwide demonstrating allelic heterogeneity. The germline mutation spectrum of APC identified in 69 apparently unrelated Norwegian FAP families are presented and discussed with reference to clinical phenotype and novel mutation rate. Different methods have been used over the years. However, all mutations were confirmed detectable by an implemented denaturing high-performance liquid chromatography screening approach. Multiplex ligation-dependent probe amplification analysis was employed for potential gross rearrangements. Fifty-three distinctive mutations were detected, of which 22 have been detected in Norway exclusively. Except for two major deletion mutations encompassing the entire APC, all mutations resulted in premature truncation of translation caused by non-sense (31%) or change in reading frame (69%). A high ratio of novel APC mutations continues to contribute to APC mutation heterogeneity causing FAP. This is the first comprehensive report of APC germline mutation spectrum in Norway.

  10. Wind / hydro complementary seasonal regimes in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Amarante, O.A.C. do [CAMARGO SCHUBERT Engenharia Eolica, Curitiba PR (Brazil); Schultz, D.J. [Companhia Paranaense de Energia (COPEL), Curitiba, PR (Brazil); Bittencourt, R.M. [CHESF - Companhia Hidro Eletrica do Sao Francisco, Recife PE (Brazil); Rocha, N.A. [PROMON Engenharia Ltda., Rio de Janeiro, RJ (Brazil)

    2001-08-01

    In the last decades, wind power generation has proven its suitability to the Gigawatt scale, necessary to an effective contribution to electric systems. This paper demonstrates, from existing data, the wind / hydro seasonal complementarity in the relevant areas of Brazil, and discusses its possible effect on the feasibility of seasonal stabilization of the energy supply in the Brazilian interconnected grid, taking advantage of the country's large natural resources available. Case studies for the southern/southeastern and the northeastern regions of Brazil are presented. A brief analysis is included regarding the geographic location of the interconnected grid, main hydro power plants, and estimated promising wind farm areas in Brazil. (orig.)

  11. Purging deleterious mutations under self fertilization: paradoxical recovery in fitness with increasing mutation rate in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Levi T Morran

    Full Text Available BACKGROUND: The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci. METHODOLOGY/PRINCIPAL FINDINGS: We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase. CONCLUSIONS: Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. The prolonged maintenance of tightly linked compensatory and deleterious mutations facilitated by self-fertilization may be responsible for the fitness increase as linkage disequilibrium between the compensatory and deleterious mutations preserves their epistatic interaction.

  12. A novel de novo exon 21 DNMT1 mutation causes cerebellar ataxia, deafness, and narcolepsy in a Brazilian patient.

    Science.gov (United States)

    Pedroso, José Luiz; Povoas Barsottini, Orlando Graziani; Lin, Ling; Melberg, Atle; Oliveira, Acary S B; Mignot, Emmanuel

    2013-08-01

    Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges. Clinical and genetic investigation in a patient and family members. Ataxia clinic, São Paulo, Brazil. One patient and her family members. N/A. Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06:02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. The patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. The proband had a novel DNMT1 mutation in exon 21, p.Cys596Arg, c.1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient. The Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. The mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis.

  13. Mapping Mutations on Phylogenies

    DEFF Research Database (Denmark)

    Nielsen, Rasmus

    2005-01-01

    This chapter provides a short review of recent methodologies developed for mapping mutations on phylogenies. Mapping of mutations, or character changes in general, using the maximum parsimony principle has been one of the most powerful tools in phylogenetics, and it has been used in a variety...... uncertainty in the mapping. Recently developed probabilistic methods can incorporate statistical uncertainty in the character mappings. In these methods, focus is on a probability distribution of mutational mappings instead of a single estimate of the mutational mapping....

  14. Mutational landscape of yeast mutator strains.

    Science.gov (United States)

    Serero, Alexandre; Jubin, Claire; Loeillet, Sophie; Legoix-Né, Patricia; Nicolas, Alain G

    2014-02-04

    The acquisition of mutations is relevant to every aspect of genetics, including cancer and evolution of species on Darwinian selection. Genome variations arise from rare stochastic imperfections of cellular metabolism and deficiencies in maintenance genes. Here, we established the genome-wide spectrum of mutations that accumulate in a WT and in nine Saccharomyces cerevisiae mutator strains deficient for distinct genome maintenance processes: pol32Δ and rad27Δ (replication), msh2Δ (mismatch repair), tsa1Δ (oxidative stress), mre11Δ (recombination), mec1Δ tel1Δ (DNA damage/S-phase checkpoints), pif1Δ (maintenance of mitochondrial genome and telomere length), cac1Δ cac3Δ (nucleosome deposition), and clb5Δ (cell cycle progression). This study reveals the diversity, complexity, and ultimate unique nature of each mutational spectrum, composed of punctual mutations, chromosomal structural variations, and/or aneuploidies. The mutations produced in clb5Δ/CCNB1, mec1Δ/ATR, tel1Δ/ATM, and rad27Δ/FEN1 strains extensively reshape the genome, following a trajectory dependent on previous events. It comprises the transmission of unstable genomes that lead to colony mosaicisms. This comprehensive analytical approach of mutator defects provides a model to understand how genome variations might accumulate during clonal evolution of somatic cell populations, including tumor cells.

  15. Calibração das câmaras de ionização para feixes de tomografia computadorizada no Brasil: a realidade atual Calibration of ionization chambers for computed tomography beams in Brazil: the present reality

    Directory of Open Access Journals (Sweden)

    Ana Figueiredo Maia

    2006-06-01

    Full Text Available OBJETIVO: O objetivo deste trabalho foi estabelecer, no Laboratório de Calibração de Instrumentos do Instituto de Pesquisas Energéticas e Nucleares, uma metodologia de calibração específica para as câmaras de ionização tipo lápis, que são utilizadas em procedimentos dosimétricos em feixes de tomografia computadorizada, seguindo as mais recentes recomendações internacionais. MATERIAIS E MÉTODOS: Foram utilizados, neste estudo, um equipamento de radiação X industrial, várias câmaras de ionização, um sistema de colimação móvel (tipo diafragma e vários filtros de alumínio de alta pureza. RESULTADOS: Foram estabelecidos os campos padrões de radiodiagnóstico descritos na norma internacional IEC 61267, e foi elaborado um procedimento de calibração adequado para as câmaras de ionização tipo lápis. CONCLUSÃO: Atualmente, já é possível calibrar apropriadamente as câmaras de ionização tipo lápis no Brasil. O procedimento de calibração foi definido com base nas recomendações internacionais e em testes feitos com duas metodologias distintas.OBJECTIVE: The aim of this study was to establish a calibration methodology specific for pencil ionization chambers used in computed tomography dosimetric procedures, in compliance with the most recent recommendations. The study was developed at the Calibration Laboratory of the Instituto de Pesquisas Energéticas e Nucleares. MATERIALS AND METHODS: An industrial x-ray equipment, several types of ionization chambers, a mobile collimator (diaphragm type, and several high purity aluminum filters were utilized in this study. RESULTS: Diagnostic radiology standard irradiation fields were established according to IEC 61267 standard, and an adequate calibration procedure for pencil ionization chambers was elaborated. CONCLUSION: The appropriate calibration of pencil ionization chambers is already a reality in Brazil. The calibration procedure was defined on the basis of

  16. Canavan disease: a novel mutation.

    Science.gov (United States)

    Schober, Harald; Luetschg, Juerg; Hoeliner, Isabella; Kalb, Stefanie; Simma, Burkhard

    2011-10-01

    Canavan disease, an autosomal recessive inherited leukodystrophy caused by an aspartoacylase deficiency, is common among children of Ashkenazi Jewish descent. We report on a non-Jewish female infant who presented at age 6 months with progressive macrocephaly and developmental delay. A sequence analysis of the aspartoacylase gene revealed compound heterozygosity for a known mutation and for the mutation c.432G>A in exon 2, which has not yet been described in Canavan disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The invasive MenC cc103 lineage with penicillin reduced susceptibility persisting in Brazil.

    Science.gov (United States)

    Fonseca, Érica L; Marin, Michel A; Freitas, Fernanda S; Vitório, Bruna S A; de Araújo, Flávio M G; Camargo, Dhian R A; Coimbra, Roney S; De Filippis, Ivano R; Vicente, Ana Carolina P

    2017-09-01

    Penicillin is the antibiotic of choice for the treatment of meningococcal infections, and mutations in penA gene are involved with reduced susceptibility (pen(I)) emergence to this antibiotic. This study aimed to characterize the penA allelic diversity, their association with pen(I) phenotype and distribution among prevalent meningococci serogroups in Brazil. The entire penA from 49 invasive strains of distinct serogroups circulating in Brazil for more than two decades were obtained by PCR and sequencing. Additionally, the penA from 22 publicly available complete Neisseria meningitidis genomes from Brazil were included in the study. The allelic diversity was determined and a genetic tree was built using the penA sequence alignment. The penicillin MIC was obtained by the E-Test method. In general, the identified penA alleles correlated with the observed pen(I) phenotype. The canonical penA1 was the most prevalent allele, however, several altered penA were also identified in strains presenting increased penicillin MICs. It was identified a new penA amino acid position (residue 480) that possibly influence the penicillin MIC in some strains. Interestingly, the altered penA14 was found in pen(I) invasive MenC cc103 strains spread in Brazil and persisting since 2011, indicating that the biological cost imposed by pen(I) phenotype can be ameliorated by particular features present in this lineage, which represents an additional public health threat. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. UV Signature Mutations

    Science.gov (United States)

    2014-01-01

    Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta-analysis discusses signatures and their proper use. We first distinguish between a mutagen's canonical mutations – deviations from a random distribution of base changes to create a pattern typical of that mutagen – and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the non-transcribed strand or at the 3' pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non-UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; non-signature mutations induced by UV may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  19. Mutations found in the Danish population causing Hereditary Hemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Brusgaard, Klaus

    2011-01-01

    been performing genetic screening of patients and relatives with HHT. The molecular genetic screening serves dual purposes, a) as part of the clinical management as genotype/phenotype correlations exists, b) to identify asymptomatic family members. Materials and Methods Inclusion of patient’s who were....... Results In 61 families we found mutations in either ENG (N=35) or ACVLR1 (N=26). In ENG a total of 22 different mutations were found 16 was unreported. In ACVLR1 24 different mutations were found 13 was unreported. The mutations were mainly of a familial character all though in ENG a single mutation...... is present in 11 families and 2 mutations are represented in 2 families. Likewise in ACVLR1 2 mutations was found in 2 different families. I ENG 1 and in ACVLR1 3 families had major deletions found by MLPA. No mutations were found in MADH4. Conclusion The majority of mutations found during clinical genetic...

  20. Recurrent APC gene mutations in Polish FAP families

    Directory of Open Access Journals (Sweden)

    Pławski Andrzej

    2007-12-01

    Full Text Available Abstract The molecular diagnostics of genetically conditioned disorders is based on the identification of the mutations in the predisposing genes. Hereditary cancer disorders of the gastrointestinal tracts are caused by mutations of the tumour suppressor genes or the DNA repair genes. Occurrence of recurrent mutation allows improvement of molecular diagnostics. The mutation spectrum in the genes causing hereditary forms of colorectal cancers in the Polish population was previously described. In the present work an estimation of the frequency of the recurrent mutations of the APC gene was performed. Eight types of mutations occurred in 19.4% of our FAP families and these constitute 43% of all Polish diagnosed families.

  1. The deep-sea shrimp fishery off Brazil (Decapoda: Aristeidae: development and present status La pesquería de gambas de profundidad en Brasil (Decapoda: Aristeidae: desarrollo y estado actual

    Directory of Open Access Journals (Sweden)

    Rodrigo Dallagnolo

    2009-01-01

    Full Text Available The development of a deep-sea fishery for aristeid shrimps off Brazil is reviewed from its early days in 2002. Descriptive data were collected by observers on board 75 directed fishing trips conducted in the study period, with a total of over 15,000 monitored trawls. An incipient fishing phase took place between No-vember 2000 and October 2002, when aristeid shrimps were occasionally reported in the bycatch of operations mostly targeting the Argentine hake (Merluccius hubbsi. After that, a directed fishery was established for these resources. All nine vessels involved in this fishery (one national and eight chartered concentrated on 11 limited grounds between 700 and 800 m deep and 18°S and 34°S. The main species caught between November 2002 and May 2007 was the "carabinero" Aristaeopsis edwardsiana (456,710 kg, followed by the "moruno" Aristaeomorpha foliácea (121,497 kg, and then the "alistado" Aristeus antillensis (27,919 kg. The trawlers operate in conjunction, such that the total area of each fishing ground was swept at least twice. This harvest pattern substantially reduced "carabinero" catch rates from 14 kg hour-1 in the first sampled trimester to 4 kg hour-1 in the last. Despite the inferred biomass reduction of this species, the fishery has continued without a formal management plan.Se revisa el desarrollo de una pesquería en aguas profundas dirigida a gambas aristeideas en Brasil. Desde su inicio, en 2002, los datos descriptivos fueron obtenidos por observadores a bordo de 75 viajes de pesca realizadas en ese período que resultaron en más de 15.000 arrastres monitoreados. Una fase incipiente de la pesquería se estableció entre noviembre de 2000 y octubre de 2002, cuando gambas aristeideas fueron registradas en la captura accidental de operaciones de pesca dirigidas principalmente a la merluza-argentina (Merluccius hubbsi. A ésta sobrevino una fase dirigida en que participaron nueve arrastreros (uno nacional y ocho arrendados

  2. Spherical tokamak development in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, G.O.; Del Bosco, E.; Ferreira, J.G.; Berni, L.A.; Oliveira, R.M.; Andrade, M.C.R.; Shibata, C.S.; Ueda, M.; Barroso, J.J.; Castro, P.J. [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Lab. Associado de Plasma; Barbosa, L.F.W. [Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, SP (Brazil). Faculdade de Engenharia, Arquitetura e Urbanismo; Patire Junior, H. [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Div. de Mecanica Espacial e Controle; The high-power microwave sources group

    2003-12-01

    This paper describes the general characteristics of spherical tokamaks, or spherical tori, with a brief overview of work in this area already performed or in progress at several institutions worldwide. The paper presents also the steps in the development of the ETE (Experimento Tokamak Esferico) project, its research program, technical characteristics and operating conditions as of December, 2002 at the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  3. Spherical tokamak development in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Gerson Otto; Bosco, Edson Del; Ferreira, Julio Guimaraes [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Lab. Associado de Plasma] (and others)

    2003-07-01

    The general characteristics of spherical tokamaks, or spherical tori, with a brief view of work in this area already performed or in progress at several institutions worldwide are described. The paper presents also the steps in the development of the ETE (Experiment Tokamak spheric) project, its research program, technical characteristics and operating conditions as of December, 2002 a the Associated Plasma Laboratory (LAP) of the National Space Research Institute (INPE) in Brazil. (author)

  4. [Family medicine in Brazil].

    Science.gov (United States)

    Abath, G M

    1985-01-01

    A need for general physicians, chiefly to deal with health problems in the interior, has made itself felt since 1948. The first two medical residency programs for the training of general physicians were begun in 1976, and today there are 13 such programs. Ten of those programs have been studied in this report, which is based on visits to the establishments where the resident physicians receive training and to some areas served by the programs, and on interviews with education and health officials, alumni of the programs, resident physicians, and coordinators and supervisors of residency programs. "Community general medicine" is the term most widely used in the profession to designate medical practice addressed to the individual, the family and the community and providing total, ongoing and personalized care of the patient. Community general medicine must take account of psychological and socioeconomic factors and interact with the community to collaborate in the solution of its problems. The residency programs in community general medicine are essential for the training of teachers and researchers who will be models to the graduating students and change the undergraduate courses by removing them from the now prevalent overspecialization so as to arrive at a more humane medicine that is more responsive to the health needs of less developed regions. For lack of information on the practice and teaching of community general medicine, attitudes in the medical profession vary from apathetic to sceptical to approving. As a new movement in Brazil, it has great difficulties to overcome, including shortcomings in the training for it and a lack of job openings for graduates. Up to 1982, 174 physicians had completed residencies in community general medicine in Brazil, and about 154 of them are known to have been employed. There are at present 138 physicians attending the 10 programs considered. The regular teaching staff are joined by many professionals in different capacities

  5. Fitness is strongly influenced by rare mutations of large effect in a microbial mutation accumulation experiment.

    Science.gov (United States)

    Heilbron, Karl; Toll-Riera, Macarena; Kojadinovic, Mila; MacLean, R Craig

    2014-07-01

    Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments. We performed a classic MA experiment in which frequent sampling of MA lines was combined with whole genome resequencing to develop a high-resolution picture of the effect of spontaneous mutations in a hypermutator (ΔmutS) strain of the bacterium Pseudomonas aeruginosa. After ∼644 generations of mutation accumulation, MA lines had accumulated an average of 118 mutations, and we found that average fitness across all lines decayed linearly over time. Detailed analyses of the dynamics of fitness change in individual lines revealed that a large fraction of the total decay in fitness (42.3%) was attributable to the fixation of rare, highly deleterious mutations (comprising only 0.5% of fixed mutations). Furthermore, we found that at least 0.64% of mutations were beneficial and probably fixed due to positive selection. The majority of mutations that fixed (82.4%) were base substitutions and we failed to find any signatures of selection on nonsynonymous or intergenic mutations. Short indels made up a much smaller fraction of the mutations that were fixed (17.4%), but we found evidence of strong selection against indels that caused frameshift mutations in coding regions. These results help to quantify the amount of natural selection present in microbial MA experiments and demonstrate that changes in fitness are strongly influenced by rare mutations of large effect. Copyright © 2014 by the Genetics Society of America.

  6. Single Mutation in Shine-Dalgarno-Like Sequence Present in the Amino Terminal of Lactate Dehydrogenase of Plasmodium Effects the Production of an Eukaryotic Protein Expressed in a Prokaryotic System

    NARCIS (Netherlands)

    Cicek, M.; Mutlu, O.; Erdemir, A.; Ozkan, E.; Saricay, Y.; Turgut-Balik, D.

    2013-01-01

    One of the most important step in structure-based drug design studies is obtaining the protein in active form after cloning the target gene. In one of our previous study, it was determined that an internal Shine-Dalgarno-like sequence present just before the third methionine at N-terminus of wild

  7. Pediatric lymphomas in Brazil

    Directory of Open Access Journals (Sweden)

    Gabriela Gualco

    2010-01-01

    Full Text Available OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36% and mature (64% cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%, followed by diffuse large B-cell lymphomas (24%. In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%, followed by peripheral T-cell lymphoma, then not otherwise specified (25%. In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%. Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions.

  8. IDRC in Brazil

    International Development Research Centre (IDRC) Digital Library (Canada)

    biotechnology and nanotechnology could help to develop natural resources in a more sustainable way. □ Reconstruction in Haiti. Funding: $300,700. Duration: 2009–2012. Grantee: Pró-Ensino Sociedade Civil, Brazil. Researchers from Brazil, Argentina, Mexico, and Chile have been supporting their coun- tries' efforts to ...

  9. A new PAX6 mutation in familial aniridia.

    OpenAIRE

    Hanson, I.; Brown, A.; Van Heyningen, V.

    1995-01-01

    Aniridia (lack of iris) is caused by loss of function mutations in one copy of the PAX6 gene. Here we present a new PAX6 splice mutation in a family with autosomal dominant aniridia. The mutation is a single nucleotide change which, although occurring within an exon, affects the splice junction consensus and results in skipping of that exon.

  10. Titin mutation in familial restrictive cardiomyopathy

    National Research Council Canada - National Science Library

    Peled, Yael; Gramlich, Michael; Yoskovitz, Guy; Feinberg, Micha S; Afek, Arnon; Polak-Charcon, Sylvie; Pras, Elon; Sela, Ben-Ami; Konen, Eli; Weissbrod, Omer; Geiger, Dan; Gordon, Paul M K; Thierfelder, Ludwig; Freimark, Dov; Gerull, Brenda; Arad, Michael

    2014-01-01

    ...). Other genes associated with RCM include the desmin and familial amyloidosis genes. In the present study we describe familial RCM with severe heart failure triggered by a de novo mutation in TTN, encoding the huge muscle filament protein titin...

  11. Delivery presentations

    Science.gov (United States)

    ... is delivered under the pubic bone. After the shoulder, the rest of the body is usually delivered without a problem. Alternative Names Shoulder presentation; Malpresentations; Breech birth; Cephalic presentation; Fetal lie; ...

  12. Mitochondrial DNA mutation load in a family with the m.8344A>G point mutation and lipomas

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Al-Hashimi, Noor; Duno, Morten

    2017-01-01

    Studies have shown that difference in mtDNA mutation load among tissues is a result of postnatal modification. We present five family members with the m.8344A>G with variable phenotypes but uniform intrapersonal distribution of mutation load, indicating that there is no postnatal modification of mt......DNA mutation load in this genotype....

  13. Mutation of human cells by kerosene soot

    Energy Technology Data Exchange (ETDEWEB)

    Skopek, T.R. (Massachusetts Inst. of Tech., Cambridge, MA); Liber, H.L.; Kaden, D.A.; Hites, R.A.; Thilly, W.G.

    1979-08-01

    The polycyclic aromatic hydrocarbon fraction of a kerosene soot induced forward mutation in human diploid lymphoblasts when coincubated with coincubated with Sprague-Dawley rat liver postmitochondrial supematant. Two components of the kerosene soot extract, benzo(a)pyrene (BP) and cyclopenta(cd)pyrene (CP), were also tested. BP was not mutagenic at the concentration found in the soot extract, although it was active at higher concentrations. The amount of CP present could account for approximately 8% of the total mutation observed with the soot. The results were compared to data obtained previously in a similar mutation assay in Salmonella typhimurium. the protocol described permits the facile assay of mutation at the hgprt locus in human lymphoblasts; such mutation is induced by compounds or complex mixtures requiring mixed-function oxygenase activity for metabolism to genetically active derivatives.

  14. Hereditary Pancreatitis Associated With the N29T Mutation of the PRSS1 Gene in a Brazilian Family: A Case-Control Study.

    Science.gov (United States)

    Dytz, Marcio Garrison; Mendes de Melo, Julia; de Castro Santos, Olga; da Silva Santos, Isabel Durso; Rodacki, Melanie; Conceição, Flavia Lucia; Ortiga-Carvalho, Tania Maria

    2015-09-01

    Hereditary pancreatitis (HP) is an autosomal-dominant disease with incomplete penetrance manifesting as early-onset chronic relapsing pancreatitis. A mutation in the PRSS1 gene is present in greater than 70% of HP kindreds and leads to a gain-of-function characterized by the increased autocatalytic conversion of trypsinogen to active trypsin, promoting autodigestion and damage to acinar cells. Other genetic defects observed in the pathogenic mechanism of pancreatitis include mutations in the genes encoding SPINK1, CTRC, and CPA1. There are few reports of HP in Latin America, and no families have been investigated in Brazil. A case-control observational study was conducted at Clementino Fraga Filho University Hospital in Brazil. Patients with suspected HP and healthy controls were enrolled in this study, and a detailed questionnaire was administered to patients with HP. PRSS1 and SPINK1 genes were analyzed by DNA sequencing, and a family that fit the HP diagnostic criteria was identified. The neutral polymorphism c.88-352A > G in the SPINK1 gene was found to be prevalent in the individuals studied, but no important alterations were found in this gene. Ten out of 16 individuals in this family carried the N29T mutation in the PRSS1 gene, with 2 clinically unaffected mutation carriers. The median age of HP onset was 6 years. Pancreatic exocrine failure occurred in 6 patients, 5 of whom also had diabetes mellitus. Surgical procedures were performed on 3 affected members, and no cases of pancreatic cancer have been reported thus far. This study identified the first PRSS1 gene mutation in a Brazilian family with HP.

  15. Multiple mutations and mutation combinations in the sodium channel of permethrin resistant mosquitoes, Culex quinquefasciatus

    Science.gov (United States)

    Li, Ting; Zhang, Lee; Reid, William R.; Xu, Qiang; Dong, Ke; Liu, Nannan

    2012-10-01

    A previous study identified 3 nonsynonymous and 6 synonymous mutations in the entire mosquito sodium channel of Culex quinquefasciatus, the prevalence of which were strongly correlated with levels of resistance and increased dramatically following insecticide selection. However, it is unclear whether this is unique to this specific resistant population or is a common mechanism in field mosquito populations in response to insecticide pressure. The current study therefore further characterized these mutations and their combinations in other field and permethrin selected Culex mosquitoes, finding that the co-existence of all 9 mutations was indeed correlated with the high levels of permethrin resistance in mosquitoes. Comparison of mutation combinations revealed several common mutation combinations presented across different field and permethrin selected populations in response to high levels of insecticide resistance, demonstrating that the co-existence of multiple mutations is a common event in response to insecticide resistance across different Cx. quinquefasciatus mosquito populations.

  16. IDH1 mutated low grade astrocytoma occurring in MSH2 mutated Lynch syndrome family

    Directory of Open Access Journals (Sweden)

    Alaa Alkhotani

    2016-12-01

    Full Text Available Lynch syndrome (LS is an autosomal dominant tumour predisposition syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR genes.Patients with these mutations have an increased risk of brain tumours, the vast majority of which are glioblastomas and medulloblastomas, and their occurrence has been termed Turcot Syndrome. The case presented herein of a member of a Lynch syndrome family with an MSH2 mutation expands the spectrum of brain tumours occurring in Lynch syndrome to include low grade astrocytomas, and is the first reported case of an IDH1 (R132H mutated brain tumour occurring in a Lynch syndrome family.

  17. Lower genetic variability of HIV-1 and antiretroviral drug resistance in pregnant women from the state of Pará, Brazil.

    Science.gov (United States)

    Machado, Luiz Fernando Almeida; Costa, Iran Barros; Folha, Maria Nazaré; da Luz, Anderson Levy Bessa; Vallinoto, Antonio Carlos Rosário; Ishak, Ricardo; Ishak, Marluisa Oliveira Guimarães

    2017-04-12

    The present study aimed to describe the genetic diversity of HIV-1, as well as the resistance profile of the viruses identified in HIV-1 infected pregnant women under antiretroviral therapy in the state of Pará, Northern Brazil. Blood samples were collected from 45 HIV-1 infected pregnant to determine the virus subtypes according to the HIV-1 protease (PR) gene and part of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of these regions. Drug resistance mutations and susceptibility to antiretroviral drugs were analyzed by the Stanford HIV Drug Resistance Database. Out of 45 samples, only 34 could be amplified for PR and 30 for RT. Regarding the PR gene, subtypes B (97.1%) and C (2.9%) were identified; for the RT gene, subtypes B (90.0%), F (6.7%), and C (3.3%) were detected. Resistance to protease inhibitors (PI) was identified in 5.8% of the pregnant, and mutations conferring resistance to nucleoside reverse transcriptase inhibitors were found in 3.3%, while mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors were found in 3.3%. These results showed a low frequency of strains resistant to antiretroviral drugs, the prevalence of subtypes B and F, and the persistent low transmission of subtype C in pregnant of the state of Pará, Brazil.

  18. Study of mutations in Jordanian patients with haemophilia A: identification of five novel mutations.

    Science.gov (United States)

    Awidi, A; Ramahi, M; Alhattab, D; Mefleh, R; Dweiri, M; Bsoul, N; Magablah, A; Arafat, E; Barqawi, M; Bishtawi, M; Haddadeen, E; Falah, M; Tarawneh, B; Swaidan, S; Fauori, S

    2010-01-01

    Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the factor VIII gene (F8), which encodes factor VIII (FVIII) protein, a plasma glycoprotein, that plays an important role in the blood coagulation cascade. In the present study, our aim was to identify F8 gene mutations in HA patients from Jordan. One hundred and seventy-five HA patients from 42 unrelated families were included in this study. Among these patients, 117 (67%) had severe HA, 13 (7%) had moderate HA and 45 (26%) had mild HA. Severe patients were first tested for intron-22 inversion using long range polymerase chain reaction (PCR), then negative patients were tested for intron-1 inversion using PCR. Sequencing for the entire F8 gene was performed for all severe HA patients who were found negative for intron-22 and -1 inversions and it was also performed for moderate and mild HA patients. HA causative mutations were identified in all patients. Intron-22 and -1 inversions were detected in 52% and 2% of families respectively. Beside these two mutations, 19 different mutations were identified, which include 15 missense and four frameshift mutations. Five novel mutations were identified including one frameshift and four missense mutations. No large deletions or nonsense mutations were detected in patients who participated in this study. Only 17 patients with severe HA were found positive for FVIII inhibitors. The data presented will play an important role for genetic counselling and health care of HA patients in Jordan.

  19. Single mutation in Shine-Dalgarno-like sequence present in the amino terminal of lactate dehydrogenase of Plasmodium effects the production of an eukaryotic protein expressed in a prokaryotic system.

    Science.gov (United States)

    Cicek, Mustafa; Mutlu, Ozal; Erdemir, Aysegul; Ozkan, Ebru; Saricay, Yunus; Turgut-Balik, Dilek

    2013-06-01

    One of the most important step in structure-based drug design studies is obtaining the protein in active form after cloning the target gene. In one of our previous study, it was determined that an internal Shine-Dalgarno-like sequence present just before the third methionine at N-terminus of wild type lactate dehydrogenase enzyme of Plasmodium falciparum prevent the translation of full length protein. Inspection of the same region in P. vivax LDH, which was overproduced as an active enzyme, indicated that the codon preference in the same region was slightly different than the codon preference of wild type PfLDH. In this study, 5'-GGAGGC-3' sequence of P. vivax that codes for two glycine residues just before the third methionine was exchanged to 5'-GGAGGA-3', by mimicking P. falciparum LDH, to prove the possible effects of having an internal SD-like sequence when expressing an eukaryotic protein in a prokaryotic system. Exchange was made by site-directed mutagenesis. Results indicated that having two glycine residues with an internal SD-like sequence (GGAGGA) just before the third methionine abolishes the enzyme activity due to the preference of the prokaryotic system used for the expression. This study emphasizes the awareness of use of a prokaryotic system to overproduce an eukaryotic protein.

  20. Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors

    Directory of Open Access Journals (Sweden)

    Luciana Bonome Zeminian

    2013-02-01

    Full Text Available The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3 have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

  1. Energetic infrastructure and sustainable development: present situation and alternatives for the state of Roraima, Brazil; Infraestrutura energetica e desenvolvimento sustentavel: situacao atual e alternativas para o estado de Roraima, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Antonio de Oliveira

    2009-07-01

    This study aims to analyze the current situation of energy structure available of Roraima state, as well as viable alternatives to enlarge the base of the structure and minimize the impact to the environment, thus providing the support necessary for sustainable development of the state. In the theoretical framework, sought to present the main links between natural resources, economy and environment, and between infrastructure and economic development, where it is present energy infrastructure. Examined the capacity of generating electricity in Roraima and the existent limitations of the current structure available. Verifying the available options for energy production from renewable source in the state, analyzing their potential and viability. Were also proposed for energy planning strategies with the goal of providing the essential foundation for the sustainable development of Roraima. As a result of the search is highlighted the source of energy with the greatest potential in the state is water. The biomass and solar energy can be alternatives to attend isolated communities. The study also found that the current structure of energy Roraima does not provide the support necessary for a reliable and sustainable development. (author)

  2. CATCHY PRESENTATIONS

    DEFF Research Database (Denmark)

    Eriksen, Kaare; Tollestrup, Christian; Ovesen, Nis

    2011-01-01

    and ideas in many areas and avoiding “Death by Powerpoint”. This paper discusses the need and tools for making short presentations and describes the result from a business development project where engineering graduate students in architecture and design used the Pecha Kucha format to present...

  3. A new species of the genus Xanthomicrogaster Cameron (Hymenoptera: Braconidae: Microgastrinae) from Brazil

    NARCIS (Netherlands)

    Penteado-Dias, A.M.; Shimabukuro, P.H.F.; Achterberg, van C.

    2002-01-01

    One new Xanthomicrogaster species from Brazil is described, and X. fortipes Cameron, 1911, is redescribed and reported from Brazil and Suriname for the first time. A key to the species is presented as well as data about the geographical distribution in Brazil.

  4. Climatic change in northeastern Brazil: paleoparasitological data

    Directory of Open Access Journals (Sweden)

    Adauto Araujo

    1993-12-01

    Full Text Available Trichuris eggs were observed in Kerodon rupestris coprolites dated 9,000 years before present, collected in archeological sites of São Raimundo Nonato, northeastern Brazil. However, present day local rodents seem not to be infected by the parasite, suggesting its disappearence due to climatic changes.

  5. THE COOPERATIVE CREDIT MUTUAL IN BRAZIL.

    Directory of Open Access Journals (Sweden)

    Laércio Baptista da Silva

    2013-06-01

    Full Text Available This study presents an analysis of the reality of credit unions in Brazil, in view of the singular importance of credit unions for the whole society as an alternative to private resources in favor of members of the community where they are located. It confirms that, in Brazil, the mutual credit unions, besides being presented as one of the viable options within the financial system, are also seen as an alternative by which some sectors of society promote the humanization of the financial system by offering credit and return on capital with fairer interest rates.

  6. Situação atual da filariose bancroftiana na cidade de Maceió, estado de Alagoas, Brasil Present status of bancroftian filariasis in Maceió, State of Alagoas, Brazil

    Directory of Open Access Journals (Sweden)

    Gilberto Fontes

    Full Text Available Com o objetivo de determinar a prevalência e a distribuição da filariose linfática bancroftiana na área urbana de Maceió, estado de Alagoas, assim como identificar os insetos vetores na região, foram realizados inquéritos hemoscópicos e entomológicos. Foram examinadas, pelo método da gota espessa, amostras de sangue de 10.450 escolares oriundos de diferentes regiões da cidade, sendo detectado 0,66% de indivíduos microfilarêmicos por Wuchereria bancrofti. A parasitose tem distribuição focal com 80% dos indivíduos com infecção patente detectados em duas regiões vizinhas, cujas prevalências atingiram 1,24% e 5,25%. Estudos paralelos feitos em amostras populacionais com indivíduos de diferentes faixas etárias mostraram prevalências semelhantes às detectadas entre os escolares. No entanto, o exame dos familiares de indivíduos infectados pela W. bancrofti mostrou prevalência seis vezes mais alta, sugerindo maior transmissão no intradomicílio. A percentagem de parasitados foi maior no grupo etário mais jovem (Epidemiological and entomological surveys were carried out in the human and mosquito populations in Maceió, Alagoas, in order to assess the present status of bancroftian lymphatic filariasis. Examination of thick blood smears of 10,450 students from different areas of the city revealed 0.66% Wuchereria bancrofti microfilaria carriers. The distribution of filariasis is focal in the city, 80% of the individuals with patent infection living in two neighboring areas with 1.24% and 5.25% prevalence. Parallel studies performed with samples of all age groups in the human population showed similar microfilaria prevalence rates observed previously in the student survey. However, thick blood smears taken from members of families with at least one subject with patent infection gave a prevalence six times greater suggesting, increased transmission in households. The percentage of carriers was higher in the youngest age group

  7. Information Presentation

    Science.gov (United States)

    Holden, Kritina L.; Thompson, Shelby G.; Sandor, Aniko; McCann, Robert S.; Kaiser, Mary K.; Adelstein, Barnard D.; Begault, Durand R.; Beutter, Brent R.; Stone, Leland S.; Godfroy, Martine

    2009-01-01

    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew. In addition to addressing display design issues associated with information formatting, style, layout, and interaction, the Information Presentation DRP is also working toward understanding the effects of extreme environments encountered in space travel on information processing. Work is also in progress to refine human factors-based design tools, such as human performance modeling, that will supplement traditional design techniques and help ensure that optimal information design is accomplished in the most cost-efficient manner. The major areas of work, or subtasks, within the Information Presentation DRP for FY10 are: 1) Displays, 2) Controls, 3) Procedures and Fault Management, and 4) Human Performance Modeling. The poster will highlight completed and planned work for each subtask.

  8. Poster Presentations

    National Research Council Canada - National Science Library

    2017-01-01

    [...]high index of suspicion was observed when other 4 patients presented with biopsy proven secondary membranous with history of intake of indigenous medications and all were shown to have increased urinary mercury levels...

  9. CERN presentations

    CERN Multimedia

    CERN. Geneva

    2011-01-01

    Presentation by CERN (10 minutes each) Rolf Landua - Education and Outreach Salvatore Mele - Open Access Jean-Yves Le Meur - Digital Library in Africa Francois Fluckiger - Open Source/Standards (tbc) Tim Smith - Open Data for Science Tullio Basiglia - tbc

  10. NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described.

    Science.gov (United States)

    Guaragna, Mara S; Cleto, Thaís Lira; Souza, Marcela Lopes; Lutaif, Anna Cristina G B; de Castro, Luiz Cláudio Gonçalves; Penido, Maria Goretti Moreira Guimarães; Maciel-Guerra, Andréa T; Belangero, Vera M S; Guerra-Junior, Gil; De Mello, Maricilda P

    2016-09-01

    Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease. Direct sequencing of NPHS1 gene in four children was performed. Each patient was heterozygous for two pathogenic mutations disclosing the molecular cause of the disease in 100% of the cases. We identified six different mutations, consisting of one in-frame deletion, one frameshift, and four missense substitutions. The p.Val736Met mutation that is described here for the first time was considered pathogenic by different mutation predictive algorithms. Regardless of the type of mutation, three patients had a bad outcome and died Despite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation. Also, since we identified NPHS1 pathogenic mutations as the cause of the disease in all cases analyzed, it might be a frequent cause of CNS in the South Eastern region of Brazil, although the analysis of a larger sample is required to obtain more indicative epidemiological data. © 2015 Asian Pacific Society of Nephrology.

  11. Optimization, water reuse and biomass energy potential from waste water poultry slaughterhouse in Matelandia-Parana, Brazil; Otimizacao, reuso de agua e potencial energetico da biomassa presente nas aguas residuarias de abatedouro de aves em Matelandia, Parana

    Energy Technology Data Exchange (ETDEWEB)

    Formentini, Diana Fatima [Fundacao Parque Tecnologico de Itaipu (PTI), Foz do Iguacu, PR (Brazil)], E-mail: mpbambiental@yahoo.com.br; Costanzi, Ricardo Nagamine [Universidade Federal Tecnologica do Parana (UFTPR), PR (Brazil)

    2010-07-01

    The alternative sources for energy generation through anaerobic digestion assist in reducing emissions of greenhouse gases and increase the efficiency removing wastewater organic load. This study aimed to identify opportunities for optimization and water reuse in industry and energy potential of biomass present in wastewater from poultry slaughterhouse in Matelandia Parana state, through the anaerobic digestion process. The company slaughtered 130,000 poultries d{sup -1} and generates a wastewater flow of 3,398.77 m{sup 3}.d{sup -}1. Measurements of water consumption were made by water meters installed at seven points of the production process, which resulted in consumption values by sector. The treatment system used consists of pre-treatment in sieve flotator static and physical, followed by stabilization ponds. Two anaerobic ponds were covered with a geo membrane and installed a gas meter to measure the flow of biogas production. The average production of biogas produced in each month was approximately 2,100 m{sup 3}. The use of biomass poultry slaughterhouse is viable for generating electricity and that you can reuse 255.80 m{sup 3}.d{sup -1}. (author)

  12. Somatic mutations in cerebral cortical malformations.

    Science.gov (United States)

    Jamuar, Saumya S; Lam, Anh-Thu N; Kircher, Martin; D'Gama, Alissa M; Wang, Jian; Barry, Brenda J; Zhang, Xiaochang; Hill, Robert Sean; Partlow, Jennifer N; Rozzo, Aldo; Servattalab, Sarah; Mehta, Bhaven K; Topcu, Meral; Amrom, Dina; Andermann, Eva; Dan, Bernard; Parrini, Elena; Guerrini, Renzo; Scheffer, Ingrid E; Berkovic, Samuel F; Leventer, Richard J; Shen, Yiping; Wu, Bai Lin; Barkovich, A James; Sahin, Mustafa; Chang, Bernard S; Bamshad, Michael; Nickerson, Deborah A; Shendure, Jay; Poduri, Annapurna; Yu, Timothy W; Walsh, Christopher A

    2014-08-21

    Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.).

  13. A New Mutation in Blau Syndrome

    Directory of Open Access Journals (Sweden)

    Cengiz Zeybek

    2015-01-01

    Full Text Available Blau syndrome is a rare, autosomal dominant, granulomatous autoinflammatory disease. The classic triad of the disease includes recurrent uveitis, granulomatous dermatitis, and symmetrical arthritis. Blau syndrome is related to mutations located at the 16q12.2–13 gene locus. To date, 11 NOD2 gene mutations causing Blau syndrome have been described. Here, we describe a 5-year-old male patient who presented with Blau syndrome associated with a novel sporadic gene mutation that has not been reported previously.

  14. Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations.

    Science.gov (United States)

    Szpurka, Hadrian; Jankowska, Anna M; Makishima, Hideki; Bodo, Juraj; Bejanyan, Nelli; Hsi, Eric D; Sekeres, Mikkael A; Maciejewski, Jaroslaw P

    2010-08-01

    While a majority of patients with refractory anemia with ring sideroblasts and thrombocytosis harbor JAK2V617F and rarely MPLW515L, JAK2/MPL-negative cases constitute a diagnostic problem. 23 RARS-T cases were investigated applying immunohistochemical phospho-STAT5, sequencing and SNP-A-based karyotyping. Based on the association of TET2/ASXL1 mutations with MDS/MPN we studied molecular pattern of these genes. Two patients harbored ASXL1 and another 2 TET2 mutations. Phospho-STAT5 activation was present in one mutated TET2 and ASXL1 case. JAK2V617F/MPLW515L mutations were absent in TET2/ASXL1 mutants, indicating that similar clinical phenotype can be produced by various MPN-associated mutations and that additional unifying lesions may be present in RARS-T. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. Análise da mutação G20210A no gene da protrombina (fator II em pacientes com suspeita de trombofilia no sul do Brasil Analysis of prothrombin G20210A mutation (factor II in patients with suspected trombophilia in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Marcos Edgar Herkenhoff

    2012-04-01

    with thrombophilia. This allelic variant is a single mutation, also denominated single nucleotide polymorphism (SNP, in which guanine is replaced with adenine in the messenger ribonucleic acid (mRNA cleavage of nucleotide 20210. The replacement is characterized by the presence of allele A and the absence of mutation in allele G. OBJECTIVE: To quantify the number of individuals homozygous for allele G, allele A and heterozygotes. The samples were collected in Paraná and Santa Catarina from January 1st, 2009 to October 10th, 2010 and were sent to Genolab Análises Genéticas. METHODS: Analysis of single mutation by polymerase chain reaction in real time (RT-PCR. RESULTS: From 243 individuals, 51.03% were from Paraná and 48.97% were from Santa Catarina. 88.89% individuals were homozygous for G genotype, none of them were homozygous for A. Only 11.11% were heterozygotes. Santa Catarina presented a higher frequency in heterozygous genotype in comparison with Paraná. CONCLUSION: This study showed that patients with suspected thrombophilia should undergo genotype identification in both states.

  16. Perfil socioeconômico dos portadores de glaucoma no serviço de oftalmologia do hospital universitário da Universidade Federal de Juiz de Fora - Minas Gerais - Brasil Socioeconomic profile of individuals presenting with glaucoma in the service of ophthalmology of the University Hospital of the Federal University of Juiz de Fora - Minas Gerais - Brazil

    Directory of Open Access Journals (Sweden)

    Cristiana Moraes Ramalho

    2007-10-01

    Full Text Available OBJETIVO: Avaliação do perfil socioeconômico dos pacientes portadores de glaucoma primário em acompanhamento no serviço de oftalmologia do hospital universitário da Universidade Federal de Juiz de Fora (MG, Brasil. MÉTODOS: Aplicação de um questionário em 100 pacientes durante suas consultas no serviço de oftalmologia do hospital universitário da Universidade Federal de Juiz de Fora, no período de abril de 2005 a junho de 2006. RESULTADOS: Observou-se que 84% dos pacientes eram pensionistas ou aposentados, 86% recebiam de 1 a 2 salários mínimos, 29% gastavam de 26 a 75 reais/mês com o tratamento do glaucoma, 78% apresentavam co-morbidades e 41% já haviam suspendido o tratamento por falta de condições financeiras para a compra das medicações. CONCLUSÃO: A população em estudo, de baixo nível socioeconômico, apresenta dificuldades de adesão terapêutica por, principalmente, problemas financeiros e presença de co-morbidades. Os autores reforçam a urgente necessidade de adoção de medidas sociopolíticas que facilitem o acesso à medicação antiglaucomatosa, determinando maior aderência terapêutica.PURPOSE: To assess the socioeconomic profile of individuals presenting with primary glaucoma at the ophthalmology service of the university hospital of the Feredal University of Juiz de Fora (MG, Brazil. METHODS: Submission of a questionnaire to 100 individuals during consultation in the ophthalmology service of the university hospital of Federal University of Juiz de Fora (MG, Brazil. RESULTS: Eighty-four per cent of individuals were pensioners or retired, 86% had a monthly income of 1 to 2 salaries, 29% had been spending 26 to 75 reais per month with glaucoma therapy, 78% presented with comorbidities and 41% had already abandoned treatment due to financial difficulties in buying the medication. CONCLUSION: The low-socioeconomic-level studied population presents with therapeutic compliance difficulties mainly due to

  17. Drought preparedness in Brazil

    Directory of Open Access Journals (Sweden)

    Ana Paula A. Gutiérrez

    2014-06-01

    Full Text Available Large portions of Brazil′s Northeast have experienced an intense and prolonged drought for the majority of 2010–2013. This drought, along with other droughts that have hit the South in recent years, has sparked a new round of discussions to improve drought policy and management at the federal and state levels. To assist with these efforts, the World Bank recently conducted a series of evaluations on national and sub-national drought preparedness measures and approaches across five country case studies. This particular article presents the Brazilian case study. The work draws from interviews with key experts and stakeholders, as well as document analyses, and focuses on preparedness measures and approaches at the national and one sub-national case; the state of Ceará. The analysis shows that although there is a rich history of drought management throughout Brazil, there are short-term and long-term gaps and opportunities on which decision makers might consider focusing to improve monitoring, forecasting, and early warning systems, vulnerability/resilience and impact assessments, and mitigation and response planning measures.

  18. Minkowski Polynomials and Mutations

    Directory of Open Access Journals (Sweden)

    Mohammad Akhtar

    2012-12-01

    Full Text Available Given a Laurent polynomial f, one can form the period of f: this is a function of one complex variable that plays an important role in mirror symmetry for Fano manifolds. Mutations are a particular class of birational transformations acting on Laurent polynomials in two variables; they preserve the period and are closely connected with cluster algebras. We propose a higher-dimensional analog of mutation acting on Laurent polynomials f in n variables. In particular we give a combinatorial description of mutation acting on the Newton polytope P of f, and use this to establish many basic facts about mutations. Mutations can be understood combinatorially in terms of Minkowski rearrangements of slices of P, or in terms of piecewise-linear transformations acting on the dual polytope P* (much like cluster transformations. Mutations map Fano polytopes to Fano polytopes, preserve the Ehrhart series of the dual polytope, and preserve the period of f. Finally we use our results to show that Minkowski polynomials, which are a family of Laurent polynomials that give mirror partners to many three-dimensional Fano manifolds, are connected by a sequence of mutations if and only if they have the same period.

  19. Voting Present

    Directory of Open Access Journals (Sweden)

    James Lo

    2013-12-01

    Full Text Available During his time as a state senator in Illinois, Barack Obama voted “Present” 129 times, a deliberate act of nonvoting that subsequently became an important campaign issue during the 2008 presidential elections. In this article, I examine the use of Present votes in the Illinois state senate. I find evidence that Present votes can largely be characterized as protest votes used as a legislative tool by the minority party. Incorporating information from Present votes into a Bayesian polytomous item-response model, I find that this information increases the efficiency of ideal point estimates by approximately 35%. There is little evidence of significant moderation by Obama when Present votes are accounted for, though my results suggest that Obama’s voting record may have moderated significantly before his subsequent election to the U.S. Senate. My results also suggest that because legislative nonvoting may occur for a variety of reasons, naive inclusion of nonvoting behavior into vote choice models may lead to biased results.

  20. Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil

    OpenAIRE

    Moreira-Nunes, Caroline Aquino; Barros, Mariceli Baia Leão; do Nascimento Borges, Bárbara; Montenegro, Raquel Carvalho; Lamarão, Leticia Martins; Ribeiro, Helem Ferreira; Bona, Amanda Braga; Assumpção, Paulo Pimentel; Rey, Juan Antonio; Pinto, Giovanny Rebouças; Burbano, Rommel Rodriguez

    2014-01-01

    Background Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern a...

  1. Spectrum of small mutations in the dystrophin coding region.

    Science.gov (United States)

    Prior, T W; Bartolo, C; Pearl, D K; Papp, A C; Snyder, P J; Sedra, M S; Burghes, A H; Mendell, J R

    1995-07-01

    Duchenne and Becker muscular dystrophies (DMD and BMD) are caused by defects in the dystrophin gene. About two-thirds of the affected patients have large deletions or duplications, which occur in the 5' and central portion of the gene. The nondeletion/duplication cases are most likely the result of smaller mutations that cannot be identified by current diagnostic screening strategies. We screened approximately 80% of the dystrophin coding sequence for small mutations in 158 patients without deletions or duplications and identified 29 mutations. The study indicates that many of the DMD and the majority of the BMD small mutations lie in noncoding regions of the gene. All of the mutations identified were unique to single patients, and most of the mutations resulted in protein truncation. We did not find a clustering of small mutations similar to the deletion distribution but found > 40% of the small mutations 3' of exon 55. The extent of protein truncation caused by the 3' mutations did not determine the phenotype, since even the exon 76 nonsense mutation resulted in the severe DMD phenotype. Our study confirms that the dystrophin gene is subject to a high rate of mutation in CpG sequences. As a consequence of not finding any hotspots or prevalent small mutations, we conclude that it is presently not possible to perform direct carrier and prenatal diagnostics for many families without deletions or duplications.

  2. Diversity of ARSACS mutations in French-Canadians.

    Science.gov (United States)

    Thiffault, I; Dicaire, M J; Tetreault, M; Huang, K N; Demers-Lamarche, J; Bernard, G; Duquette, A; Larivière, R; Gehring, K; Montpetit, A; McPherson, P S; Richter, A; Montermini, L; Mercier, J; Mitchell, G A; Dupré, N; Prévost, C; Bouchard, J P; Mathieu, J; Brais, B

    2013-01-01

    The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability. Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin. A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin. The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.

  3. Technical presentation

    CERN Multimedia

    FI Department

    2008-01-01

    RADIOSPARES, the leading catalogue distributor of components (electronic, electrical, automation, etc.) and industrial supplies will be at CERN on Friday 3 October 2008 (Main Building, Room B, from 9.00 a.m. to 3.00 p.m.) to introduce its new 2008/2009 catalogue. This will be the opportunity for us to present our complete range of products in more detail: 400 000 part numbers available on our web site (Radiospares France, RS International, extended range of components from other manufacturers); our new services: quotations, search for products not included in the catalogue, SBP products (Small Batch Production: packaging in quantities adapted to customers’ requirements); partnership with our focus manufacturers; demonstration of the on-line purchasing tool implemented on our web site in conjunction with CERN. RADIOSPARES will be accompanied by representatives of FLUKE and TYCO ELECTRONICS, who will make presentations, demonstrate materials and answer any technical questio...

  4. Predicting resistance mutations using protein design algorithms.

    Science.gov (United States)

    Frey, Kathleen M; Georgiev, Ivelin; Donald, Bruce R; Anderson, Amy C

    2010-08-03

    Drug resistance resulting from mutations to the target is an unfortunate common phenomenon that limits the lifetime of many of the most successful drugs. In contrast to the investigation of mutations after clinical exposure, it would be powerful to be able to incorporate strategies early in the development process to predict and overcome the effects of possible resistance mutations. Here we present a unique prospective application of an ensemble-based protein design algorithm, K*, to predict potential resistance mutations in dihydrofolate reductase from Staphylococcus aureus using positive design to maintain catalytic function and negative design to interfere with binding of a lead inhibitor. Enzyme inhibition assays show that three of the four highly-ranked predicted mutants are active yet display lower affinity (18-, 9-, and 13-fold) for the inhibitor. A crystal structure of the top-ranked mutant enzyme validates the predicted conformations of the mutated residues and the structural basis of the loss of potency. The use of protein design algorithms to predict resistance mutations could be incorporated in a lead design strategy against any target that is susceptible to mutational resistance.

  5. Situação atual da fluoretação de águas de abastecimento público no Estado de São Paulo - Brasil The present position on fluoridation of water for human consumption in S. Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Osvaldo C. Buendia

    1983-06-01

    Full Text Available Destacando alguns fatos relacionados com a evolução da fluoretação de águas no Estado de São Paulo (Brasil, foram citadas Leis, Decretos e Portarias que amparam a incrementação do método. Foram citados os órgãos públicos que vêm dando assistência à implantação de sistemas de fluoretação, posicionando a ação desenvolvida por eles, cuja cobertura é de 25,39% do total dos municípios. Foram relacionadas nominalmente as 145 cidades com água fluoretada até o momento, com o composto utilizado, o órgão que implantou o sistema, a população beneficiada e o custo/hab./ano.With a view to bringing out some facts connected with the progress achieved in water fluoridation in the State of S. Paulo, Brazil, the paper quotes laws, decrees and other legal acts which form the basis for the spread of the method. The public agencies which are assisting in the implantation of fluoridation systems, are quoted and the action, covering 23.39% of all communities, which has been taken by them is discribed. The list of 145 communities fluoridated up to the present, the composite used, the implanting agency, the population benefited and cost/individual/year, are presented.

  6. Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil.

    Science.gov (United States)

    Carranza, Julio César; Valadares, Helder M S; D'Avila, Daniella A; Baptista, Rodrigo P; Moreno, Margoth; Galvão, Lúcia M C; Chiari, Egler; Sturm, Nancy R; Gontijo, Eliane D; Macedo, Andrea M; Zingales, Bianca

    2009-07-15

    The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, approximately 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex I) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T. cruzi II (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T. cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T. cruzi II cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite.

  7. Metátese de olefinas no Brasil: "Brazil is romping it!" Olefin metathesis in Brazil: Brazil is romping it!

    Directory of Open Access Journals (Sweden)

    José Milton E. Matos

    2007-04-01

    Full Text Available Some aspects of the olefin metathesis reactions are summarized here (types of reactions, mechanism and catalysts. In particular, the research groups that have been working on this chemistry in Brazil are presented. The main goal of this paper is to make this type of reaction more widely known in the Brazilian chemical community.

  8. Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.

    Science.gov (United States)

    Tatton-Brown, Katrina; Murray, Anne; Hanks, Sandra; Douglas, Jenny; Armstrong, Ruth; Banka, Siddharth; Bird, Lynne M; Clericuzio, Carol L; Cormier-Daire, Valerie; Cushing, Tom; Flinter, Frances; Jacquemont, Marie-Line; Joss, Shelagh; Kinning, Esther; Lynch, Sally Ann; Magee, Alex; McConnell, Vivienne; Medeira, Ana; Ozono, Keiichi; Patton, Michael; Rankin, Julia; Shears, Debbie; Simon, Marleen; Splitt, Miranda; Strenger, Volker; Stuurman, Kyra; Taylor, Clare; Titheradge, Hannah; Van Maldergem, Lionel; Temple, I Karen; Cole, Trevor; Seal, Sheila; Rahman, Nazneen

    2013-12-01

    Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome. To date, we have identified 48 individuals with EZH2 mutations. The mutations were primarily missense mutations occurring throughout the gene, with some clustering in the SET domain (12/48). Truncating mutations were uncommon (4/48) and only identified in the final exon, after the SET domain. Through analyses of clinical data and facial photographs of EZH2 mutation-positive individuals, we have shown that the facial features can be subtle and the clinical diagnosis of Weaver syndrome is thus challenging, especially in older individuals. However, tall stature is very common, reported in >90% of affected individuals. Intellectual disability is also common, present in ~80%, but is highly variable and frequently mild. Additional clinical features which may help in stratifying individuals to EZH2 mutation testing include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry. Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. As mutation testing becomes increasingly accessible and larger numbers of EZH2 mutation-positive individuals are identified, knowledge of the clinical spectrum and prognostic implications of EZH2 mutations should improve. © 2013 Wiley Periodicals, Inc.

  9. Women's motivation to become dentists in Brazil.

    Science.gov (United States)

    Kfouri, Maria G; Moyses, Samuel J; Moyses, Simone Tetu

    2013-06-01

    There has been a marked increase of women in dentistry in Brazil and in many countries around the world. The behavioral mechanisms behind the choice of career differ between men and women, and the inclination to care for others is thought by some to be more present in women than it is in men. This article discusses the reasons that lead women to choose dentistry as a profession in Brazil and the impact of feminization on the current and future profile of the profession, based on the ethics of care. The authors' review of the relevant literature published between 2000 and 2011, primarily in Brazil, suggests that whereas men have tended to choose dentistry as a good business opportunity, women have tended to base their decision on relations with other people and the flexibility of practicing the profession. Many women dentists have been found to decide to work fewer hours, report more interruptions in their activities, and have less preference to work in private practice than men dentists. In the view of service users and dental auxiliaries in Brazil, women dentists invest more time in their patients and communicate in a more pleasant, sensitive, and friendly manner. The conclusion suggests that characteristics often associated with women can affect the dental profession in Brazil by introducing greater concern with the promotion of health and other people's well-being in contrast to traditional dentistry based on curative procedures.

  10. Mutations in GABRB3

    DEFF Research Database (Denmark)

    Møller, Rikke S; Wuttke, Thomas V; Helbig, Ingo

    2017-01-01

    OBJECTIVE: To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. METHODS: We performed massive parallel sequencing...... of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs. RESULTS: We identified 22 patients with heterozygous mutations in GABRB3, including 3...... probands from multiplex families. The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy with myoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies...

  11. PRRT2 gene mutations

    Science.gov (United States)

    Gardiner, Alice R.; Bhatia, Kailash P.; Stamelou, Maria; Dale, Russell C.; Kurian, Manju A.; Schneider, Susanne A.; Wali, G.M.; Counihan, Tim; Schapira, Anthony H.; Spacey, Sian D.; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A.G.; Raskin, Salmo; Sander, Josemir W.; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M.; Wood, Nicholas W.; Hanna, Michael

    2012-01-01

    ABSTRACT Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. PMID:23077024

  12. Mutations in Lettuce Improvement

    OpenAIRE

    Mou, Beiquan

    2012-01-01

    Lettuce is a major vegetable in western countries. Mutations generated genetic variations and played an important role in the domestication of the crop. Many traits derived from natural and induced mutations, such as dwarfing, early flowering, male sterility, and chlorophyll deficiency, are useful in physiological and genetic studies. Mutants were also used to develop new lettuce products including miniature and herbicide-tolerant cultivars. Mutant analysis was critical in lettuce genomic stu...

  13. Labour Market Inequality in Brazil and India: A Comparative Brazil ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Labour Market Inequality in Brazil and India: A Comparative Brazil, Russia, India and China (BRIC) Study. Think tanks in Brazil and India ... to climate change. IDRC is investing in local solutions to address climate change-related challenges in India, including heat stress, water management, and climate-related migration.

  14. Labour Market Inequality in Brazil and India: A Comparative Brazil ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Inequality and the labour market : what can we learn from comparing India and Brazil?; project paper H (f). Rapports. Report on Policy Dialogue on Labour Market Inequality in Brazil and India : project paper G.2. Rapports. Vocational education and training (VET), inequality and the labour market in Brazil and India : a policy ...

  15. TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child - evidence for chimerism involving a common mutant founder haplotype: case report

    Science.gov (United States)

    2011-01-01

    Background Gastric adenocarcinoma is rare in children and adolescents, with about 17 cases under age 21 in the world's literature. We report a case of invasive well-differentiated metastatic gastric cancer in a Brazilian 12-year-old boy without documented familial history of cancer. Case presentation The patient, diagnosed with metastatic disease, died seven months after surgery. DNA from intra-surgical specimens revealed a TP53 mutation at codon 337 (p.R337H) in samples with neoplastic cells (dysplasia, tumor and metastasis) but not in non-transformed cells (incomplete intestinal metaplasia and non-involved celiac lymph node). In all mutation-positive tissues, p.R337H occurred on the same background, a founder allele identified by a specific haplotype previously described in Brazilian Li-Fraumeni syndrome patients. The same mutant haplotype, corresponding to a founder mutation present in 0.3% of the general population in Southern Brazil, was found in the genome of the father. Presence of this inherited haplotype in the tumor as well as in the father's germline, suggests a rare case of microchimerism in this patient, who may have harbored a small number of mutant cells originating in another individual, perhaps a dizygotic twin that died early in gestation. Conclusion This case represents one of the earliest ages at diagnosis of gastric cancer ever reported. It shows that cancer inheritance can occur in the absence of an obvious germline mutation, calling for caution in assessing early cancers in populations with common founder mutations such as p.R337H in Southern Brazil. PMID:22004116

  16. TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child - evidence for chimerism involving a common mutant founder haplotype: case report

    Directory of Open Access Journals (Sweden)

    Prolla Patricia A

    2011-10-01

    Full Text Available Abstract Background Gastric adenocarcinoma is rare in children and adolescents, with about 17 cases under age 21 in the world's literature. We report a case of invasive well-differentiated metastatic gastric cancer in a Brazilian 12-year-old boy without documented familial history of cancer. Case presentation The patient, diagnosed with metastatic disease, died seven months after surgery. DNA from intra-surgical specimens revealed a TP53 mutation at codon 337 (p.R337H in samples with neoplastic cells (dysplasia, tumor and metastasis but not in non-transformed cells (incomplete intestinal metaplasia and non-involved celiac lymph node. In all mutation-positive tissues, p.R337H occurred on the same background, a founder allele identified by a specific haplotype previously described in Brazilian Li-Fraumeni syndrome patients. The same mutant haplotype, corresponding to a founder mutation present in 0.3% of the general population in Southern Brazil, was found in the genome of the father. Presence of this inherited haplotype in the tumor as well as in the father's germline, suggests a rare case of microchimerism in this patient, who may have harbored a small number of mutant cells originating in another individual, perhaps a dizygotic twin that died early in gestation. Conclusion This case represents one of the earliest ages at diagnosis of gastric cancer ever reported. It shows that cancer inheritance can occur in the absence of an obvious germline mutation, calling for caution in assessing early cancers in populations with common founder mutations such as p.R337H in Southern Brazil.

  17. Technical presentation

    CERN Multimedia

    FP Department

    2009-01-01

    07 April 2009 Technical presentation by Leuze Electronics: 14.00 – 15.00, Main Building, Room 61-1-017 (Room A) Photoelectric sensors, data identification and transmission systems, image processing systems. We at Leuze Electronics are "the sensor people": we have been specialising in optoelectronic sensors and safety technology for accident prevention for over 40 years. Our dedicated staff are all highly customer oriented. Customers of Leuze Electronics can always rely on one thing – on us! •\tFounded in 1963 •\t740 employees •\t115 MEUR turnover •\t20 subsidiaries •\t3 production facilities in southern Germany Product groups: •\tPhotoelectric sensors •\tIdentification and measurements •\tSafety devices

  18. Estudo de mutações causadoras de cardiomiopatia hipertrófica em um grupo de pacientes no Espírito Santo, Brasil Estudio de mutaciones causadoras de cardiomiopatía hipertrófica en un grupo de pacientes en Espírito Santo, Brasil Study of mutations causing hypertrophic cardiomyopathy in a group of patients from Espirito Santo, Brazil

    Directory of Open Access Journals (Sweden)

    Júlia Daher Carneiro Marsiglia

    2010-01-01

    un grupo de pacientes en el estado de Espírito Santo, Brasil. MÉTODOS: Usando la técnica SSCP, se estudiaron 12 exones de los tres principales genes involucrados con la CH: exones 15, 20, 21, 22 y 23 del gen de la cadena pesada de la β-miosina (MYH7, exones 7, 16, 18, 22 y 24 del gen de la proteína C unida a la miosina (MYBPC3 y exones 8 y 9 del gen de la troponina T (TNNT2. RESULTADOS: Se encontraron 16 alteraciones, incluyendo dos mutaciones, una de ellas posiblemente patogénica en el gen MYBPC3 gen (p. Glu441Lys y otra patogénica ya descrita en el gen TNNT2 (p. Arg92Trp; 8 variaciones de secuencia raras y 6 variaciones de secuencia con frecuencia alélica mayor que el 1% (polimorfismos. CONCLUSIONES: Con estos datos, es posible concluir que el genotipaje de los pacientes es factible en nuestro medio. Es posible que la variante p.Glu441Lys en el exón 16 del gen MYBPC3 sea patogénica, resultando en un fenotipo más leve que el encontrado en asociación con otras mutaciones. La variante p.Arg92Trp en el exón 9 del gen TNNT2 no resulta en un fenotipo tan homogéneo como el descrito anteriormente y puede llevar a hipertrofia grave.BACKGROUND: Hypertrophic cardiomyopathy (HC is the most frequent cardiac hereditary disease, caused by mutations in sarcomere protein coding genes. Although more than 430 mutations have been identified in several continents and countries, there have been no reports of mutations in Brazil. OBJECTIVE: To carry out a genetic study to identify genetic mutations that cause HC in a group of patients in Espirito Santo, Brazil. METHODS: Using the SSCP technique, 12 exons from the three main genes involved in HC were studied: exons 15, 20, 21, 22 and 23 of the β-myosin heavy chain gene (MYH7, exons 7, 16, 18, 22 and 24 of the myosin binding protein C gene (MYBPC3 and exons 8 and 9 of troponin T gene (TNNT2. RESULTS: 16 alterations were found, including two mutations, one of them possibly pathogenic in the MYBPC3 gene (p. Glu441Lys and

  19. IBM Brazil: and environmental modern view

    Energy Technology Data Exchange (ETDEWEB)

    Cremonesi, Valter [IBM Brasil, Industria, Maquinas e Servicos Ltda., Rio de Janeiro, Rj (Brazil)

    1993-12-31

    Information of practical experiences on Environmental Affairs at IBM Brazil plant and branch offices is presented, with a modern view of the mission, resources, support, waste management, monitoring programs, recycling, energy conservation, partners programs, nature preservation 2rograms, recognitions and image. (author). 4 figs., 2 tabs.

  20. Assessing Higher Education Learning Outcomes in Brazil

    Science.gov (United States)

    Pedrosa, Renato H. L.; Amaral, Eliana; Knobel, Marcelo

    2013-01-01

    Brazil has developed an encompassing system for quality assessment of higher education, the National System of Higher Education Evaluation (SINAES), which includes a test for assessing learning outcomes at the undergraduate level, the National Exam of Student Performance (ENADE). The present system has been running since 2004, and also serves as…

  1. The Scenario of Gifted Education in Brazil

    Science.gov (United States)

    Wechsler, Solange Muglia; Fleith, Denise de Souza

    2017-01-01

    The purpose of this paper is to provide an overview of gifted education in Brazil. A scenario of the education of the gifted is presented, including the official concept of giftedness as well as programs and services available to emphasize important contributions to the area. Although there are considerable advances regarding policies, practices,…

  2. PREFACE: Brazil MRS Meeting 2014

    Science.gov (United States)

    2015-11-01

    The annual meetings, organized by the Brazilian materials research society - B-MRS, are amongst the most import discussion forums in the area of materials science and engineering in Brazil, with a growing interest from the national and international scientific society. In the last 4 years, more than 1,500 participants have attended the B-MRS meetings, promoting an auspicious environment for presentation and discussion of scientific and technological works in the materials science area. The XIII Brazilian Materials Research Society Meeting was held from 28 September to 02 October, 2014, in João Pessoa, PB, Brazil. The Meeting congregated more than 1650 participants from the whole of Brazil and from 28 other countries. More than 2100 abstracts were accepted for presentation, distributed along 19 Symposia following the format used in traditional meetings of Materials Research Societies. These involved topics such as: synthesis of new materials, computer simulations, optical, magnetic and electronic properties, traditional materials as clays and cements, advanced metals, carbon and graphene nanostructures, nanomaterials for nanostructures, energy storage systems, composites, surface engineering and others. A novelty was a symposium dedicated to innovation and technology transfer in materials research. The program also included 7 Plenary Lectures presented by internationally renowned researchers: Alberto Salleo from Stanford University, United States of America; Roberto Dovesi from Universita' degli Studi di Torino, Italy; Luís Antonio F. M. Dias Carlos from Universidade de Aveiro, Portugal; Jean Marie Dubois from Institut Jean-Lamour, France; Sir Colin Humphreys from University of Cambridge, England; Karl Leo from Technische Universität Dresden, Germany; Robert Chang from Northwestern University, Evanston, United States of America. The numbers of participants in the B-MRS meetings have been growing continuously, and in this meeting we had almost 2200 presentations

  3. A novel MERTK mutation causing retinitis pigmentosa.

    Science.gov (United States)

    Al-Khersan, Hasenin; Shah, Kaanan P; Jung, Segun C; Rodriguez, Alex; Madduri, Ravi K; Grassi, Michael A

    2017-08-01

    Retinitis pigmentosa (RP) is a genetically heterogeneous inherited retinal dystrophy. To date, over 80 genes have been implicated in RP. However, the disease demonstrates significant locus and allelic heterogeneity not entirely captured by current testing platforms. The purpose of the present study was to characterize the underlying mutation in a patient with RP without a molecular diagnosis after initial genetic testing. Whole-exome sequencing of the affected proband was performed. Candidate gene mutations were selected based on adherence to expected genetic inheritance pattern and predicted pathogenicity. Sanger sequencing of MERTK was completed on the patient's unaffected mother, affected brother, and unaffected sister to determine genetic phase. Eight sequence variants were identified in the proband in known RP-associated genes. Sequence analysis revealed that the proband was a compound heterozygote with two independent mutations in MERTK, a novel nonsense mutation (c.2179C > T) and a previously reported missense variant (c.2530C > T). The proband's affected brother also had both mutations. Predicted phase was confirmed in unaffected family members. Our study identifies a novel nonsense mutation in MERTK in a family with RP and no prior molecular diagnosis. The present study also demonstrates the clinical value of exome sequencing in determining the genetic basis of Mendelian diseases when standard genetic testing is unsuccessful.

  4. Phenylketonuria mutation analysis in Northern Ireland: A rapid stepwise approach

    Energy Technology Data Exchange (ETDEWEB)

    Zschocke, J.; Graham, C.A.; Nevin, N.C. [Queen`s Univ., Belfast (Australia)] [and others

    1995-12-01

    We present a multistep approach for the rapid analysis of phenylketonuria (PKU) mutations. In the first step, three common mutations and a polymorphic short tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex assay. In the second step, minihaplotypes combining STR and VNTR data are used to determine rare mutations likely to be present in an investigated patient, which are then confirmed by restriction enzyme analysis. The remaining mutations are analyzed with denaturant gradient-gel electrophoresis and sequencing. The first two steps together identify both mutations in 90%-95% of PKU patients, and results can be obtained within 2 d. We have investigated 121 Northern Irish families with hyperphenylalaninemia, including virtually all patients born since 1972, and have found 34 different mutations on 241 of the 242 mutant alleles. Three mutations (R408W, 165T, and F39L) account for 57.5% of mutations, while 14 mutations occur with a frequency of 1%-6%. The present analysis system is efficient and inexpensive and is particularly well suited to routine mutation analysis in a diagnostic setting. 19 refs., 5 tabs.

  5. [A better Brazil].

    Science.gov (United States)

    Lesser, Jeffrey

    2014-01-01

    Many countries in the Americas describe themselves as "nations of immigrants." In the United States, the myth of the "promised land" suggests that foreigners better themselves upon arrival because the nation is intrinsically great. In Brazil, however, the relationship between immigration and national identity is different. Many intellectuals, politicians, and cultural and economic leaders saw (and see) immigrants as improving an imperfect nation that has been tainted by the history of Portuguese colonialism and African slavery. As a result, immigrants were often hailed as saviors because they modified and improved Brazil, not because they were improved by Brazil. This "improvement" took place through absorption, mixture and with the use of increasingly flexible racial and ethnic categories.

  6. Actionable mutations in canine hemangiosarcoma.

    Directory of Open Access Journals (Sweden)

    Guannan Wang

    Full Text Available Angiosarcomas (AS are rare in humans, but they are a deadly subtype of soft tissue sarcoma. Discovery sequencing in AS, especially the visceral form, is hampered by the rarity of cases. Most diagnostic material exists as archival formalin fixed, paraffin embedded tissue which serves as a poor source of high quality DNA for genome-wide sequencing. We approached this problem through comparative genomics. We hypothesized that exome sequencing a histologically similar tumor, hemangiosarcoma (HSA, that occurs in approximately 50,000 dogs per year, may lead to the identification of potential oncogenic drivers and druggable targets that could also occur in angiosarcoma.Splenic hemangiosarcomas are common in dogs, which allowed us to collect a cohort of archived matched tumor and normal tissue samples suitable for whole exome sequencing. Mapping of the reads to the latest canine reference genome (Canfam3 demonstrated that >99% of the targeted exomal regions were covered, with >80% at 20X coverage and >90% at 10X coverage.Sequence analysis of 20 samples identified somatic mutations in PIK3CA, TP53, PTEN, and PLCG1, all of which correspond to well-known tumor drivers in human cancer, in more than half of the cases. In one case, we identified a mutation in PLCG1 identical to a mutation observed previously in this gene in human visceral AS. Activating PIK3CA mutations present novel therapeutic targets, and clinical trials of targeted inhibitors are underway in human cancers. Our results lay a foundation for similar clinical trials in canine HSA, enabling a precision medicine approach to this disease.

  7. Actionable mutations in canine hemangiosarcoma.

    Science.gov (United States)

    Wang, Guannan; Wu, Ming; Maloneyhuss, Martha A; Wojcik, John; Durham, Amy C; Mason, Nicola J; Roth, David B

    2017-01-01

    Angiosarcomas (AS) are rare in humans, but they are a deadly subtype of soft tissue sarcoma. Discovery sequencing in AS, especially the visceral form, is hampered by the rarity of cases. Most diagnostic material exists as archival formalin fixed, paraffin embedded tissue which serves as a poor source of high quality DNA for genome-wide sequencing. We approached this problem through comparative genomics. We hypothesized that exome sequencing a histologically similar tumor, hemangiosarcoma (HSA), that occurs in approximately 50,000 dogs per year, may lead to the identification of potential oncogenic drivers and druggable targets that could also occur in angiosarcoma. Splenic hemangiosarcomas are common in dogs, which allowed us to collect a cohort of archived matched tumor and normal tissue samples suitable for whole exome sequencing. Mapping of the reads to the latest canine reference genome (Canfam3) demonstrated that >99% of the targeted exomal regions were covered, with >80% at 20X coverage and >90% at 10X coverage. Sequence analysis of 20 samples identified somatic mutations in PIK3CA, TP53, PTEN, and PLCG1, all of which correspond to well-known tumor drivers in human cancer, in more than half of the cases. In one case, we identified a mutation in PLCG1 identical to a mutation observed previously in this gene in human visceral AS. Activating PIK3CA mutations present novel therapeutic targets, and clinical trials of targeted inhibitors are underway in human cancers. Our results lay a foundation for similar clinical trials in canine HSA, enabling a precision medicine approach to this disease.

  8. Geodiversity and geoconservation in Brazil

    Science.gov (United States)

    Cardozo Moreira, Jasmine; Muggler, Cristine Carole

    2014-05-01

    Brazil is a large country with a wide diversity of landscapes and geological features and has been an important world producer of mineral resources. Despite this, until the 90's of last century, there has not been much concern and policies about geological heritage and geoconservation. Only at the end of the century the National Geological Service (CPRM) included the physical characterization of areas with geotouristic interest in its mission of generation and diffusion of geological information. In 1997, was created the Brazilian Commission of Geological and Paleobiological Sites (SIGEP, http://sigep.cprm.gov.br), responsible for the assessment, description and publicizing the sites of geological heritage. This is by now the most comprehensive and relevant initiative to protect the national heritage. It is composed by a fully accessible national database composed by 167 certified sites presented as scientific papers. Furthermore, a web-based applicative for the inventory and protection of geological heritage sites is being developed by the National Geological Service. The wider knowledge about geological heritage can be a useful tool for its conservation and this has been an important goal in the creation of protected areas, by means of environmental education and tourism. In Brazil, actions, research and publications about the subject have increased in the last five years, as well as the outreach and responsible use of the geological heritage. Scientific meetings, conferences and courses are growing and spreading around the country. The main scientific meeting has been the Brazilian Symposium of Geological Heritage that in its second edition (2013) had more than 200 papers presented. At that meeting it was also created the Association in Defence of the Geomining Heritage and the Association of Aspiring Geoparks. Brazil has only one geopark in the Unesco's Global Geopark Network, that is the Araripe Geopark, created in 2006. By the moment, propositions are being

  9. The development of Analytical Chemistry in Brazil: retrospective and expectations

    Directory of Open Access Journals (Sweden)

    Zagatto Elias A. G.

    2003-01-01

    Full Text Available The development of Analytical Chemistry in Brazil in the last century is critically evaluated in relation to international achievements. Tendencies for the next century are foreseen, especially in relation to the presently observed shifts in paradigm.

  10. Molecular Analysis of 9 Unrelated Families Presenting With Juvenile and Chronic GM1 Gangliosidosis

    Directory of Open Access Journals (Sweden)

    Marcella B. Baptista MSc

    2016-04-01

    Full Text Available GM1 gangliosidosis is a rare autosomal recessive lysosomal storage disorder with high prevalence in Brazil (1:17 000. In the present study, we genotyped 10 individuals of 9 unrelated families from the States of São Paulo and Minas Gerais diagnosed with the juvenile and chronic forms of the disease. We found the previously described p.Thr500Ala mutation in 8 alleles; c.1622-1627insG and p.Arg59His in 2 alleles (the latter also segregating with c.1233+8T>C; and p.Phe107Leu, p.Leu173Pro, p.Arg201His, and p.Gly311Arg in 1 allele each. Two mutations (p.Ile354Ser and p.Thr384Ser and 1 neutral alteration (p.Pro152= are described for the first time. All patients presented as compound heterozygotes. A discussion on genotype–phenotype correlation is also presented.

  11. Flood model for Brazil

    Science.gov (United States)

    Palán, Ladislav; Punčochář, Petr

    2017-04-01

    Looking on the impact of flooding from the World-wide perspective, in last 50 years flooding has caused over 460,000 fatalities and caused serious material damage. Combining economic loss from ten costliest flood events (from the same period) returns a loss (in the present value) exceeding 300bn USD. Locally, in Brazil, flood is the most damaging natural peril with alarming increase of events frequencies as 5 out of the 10 biggest flood losses ever recorded have occurred after 2009. The amount of economic and insured losses particularly caused by various flood types was the key driver of the local probabilistic flood model development. Considering the area of Brazil (being 5th biggest country in the World) and the scattered distribution of insured exposure, a domain covered by the model was limited to the entire state of Sao Paolo and 53 additional regions. The model quantifies losses on approx. 90 % of exposure (for regular property lines) of key insurers. Based on detailed exposure analysis, Impact Forecasting has developed this tool using long term local hydrological data series (Agencia Nacional de Aguas) from riverine gauge stations and digital elevation model (Instituto Brasileiro de Geografia e Estatística). To provide most accurate representation of local hydrological behaviour needed for the nature of probabilistic simulation, a hydrological data processing focused on frequency analyses of seasonal peak flows - done by fitting appropriate extreme value statistical distribution and stochastic event set generation consisting of synthetically derived flood events respecting realistic spatial and frequency patterns visible in entire period of hydrological observation. Data were tested for homogeneity, consistency and for any significant breakpoint occurrence in time series so the entire observation or only its subparts were used for further analysis. The realistic spatial patterns of stochastic events are reproduced through the innovative use of d-vine copula

  12. Spectrum of K ras mutations in Pakistani colorectal cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Murtaza, B.N.; Bibi, A. [School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore (Pakistan); Rashid, M.U.; Khan, Y.I. [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Johar Town, Lahore (Pakistan); Chaudri, M.S. [Services Institute of Medical Sciences, Lahore (Pakistan); Shakoori, A.R. [School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore (Pakistan)

    2013-11-29

    The incidence of colorectal cancer (CRC) is increasing daily worldwide. Although different aspects of CRC have been studied in other parts of the world, relatively little or almost no information is available in Pakistan about different aspects of this disease at the molecular level. The present study was aimed at determining the frequency and prevalence of K ras gene mutations in Pakistani CRC patients. Tissue and blood samples of 150 CRC patients (64% male and 36% female) were used for PCR amplification of K ras and detection of mutations by denaturing gradient gel electrophoresis, restriction fragment length polymorphism analysis, and nucleotide sequencing. The K ras mutation frequency was found to be 13%, and the most prevalent mutations were found at codons 12 and 13. A novel mutation was also found at codon 31. The dominant mutation observed was a G to A transition. Female patients were more susceptible to K ras mutations, and these mutations were predominant in patients with a nonmetastatic stage of CRC. No significant differences in the prevalence of K ras mutations were observed for patient age, gender, or tumor type. It can be inferred from this study that Pakistani CRC patients have a lower frequency of K ras mutations compared to those observed in other parts of the world, and that K ras mutations seemed to be significantly associated with female patients.

  13. Scientific integrity in Brazil.

    Science.gov (United States)

    Lins, Liliane; Carvalho, Fernando Martins

    2014-09-01

    This article focuses on scientific integrity and the identification of predisposing factors to scientific misconduct in Brazil. Brazilian scientific production has increased in the last ten years, but the quality of the articles has decreased. Pressure on researchers and students for increasing scientific production may contribute to scientific misconduct. Cases of misconduct in science have been recently denounced in the country. Brazil has important institutions for controlling ethical and safety aspects of human research, but there is a lack of specific offices to investigate suspected cases of misconduct and policies to deal with scientific dishonesty.

  14. Ethnozoology in Brazil: current status and perspectives

    Directory of Open Access Journals (Sweden)

    Alves Rômulo RN

    2011-07-01

    Full Text Available Abstract Ancient connections between animals and human are seen in cultures throughout the world in multiple forms of interaction with the local fauna that form the core of Ethnozoology. Historically, ethnozoological publications grew out of studies undertaken in academic areas such as zoology, human ecology, sociology and anthropology - reflecting the interdisciplinary character of this discipline. The rich fauna and cultural diversity found in Brazil, with many different species of animals being used for an extremely wide diversity of purposes by Amerindian societies (as well as the descendents of the original European colonists and African slaves, presents an excellent backdrop for examining the relationships that exist between humans and other animals. This work presents a historical view of ethnozoological research in Brazil and examines its evolution, tendencies, and future perspectives. In summary, literature researches indicated that ethnozoology experienced significant advances in recent years in Brazil, although from a qualitative point of view improvement is still needed in terms of methodological procedures, taxonomic precision, and the use of quantitative techniques. A wide range of methodologies and theories are available in different areas of learning that can be put to good use in ethnozoological approaches if the right questions are asked. The challenges to studying ethnozoology in Brazil are not insignificant, and the tendencies described in the present study may aid in defining research strategies that will maintain the quantitative growth observed in the recent years but likewise foster needed qualitative improvements.

  15. Lateritic nickel deposits of Brazil

    Science.gov (United States)

    de Oliveira, S. M. Barros; Trescases, J. J.; Melfi, A. José

    1992-03-01

    Many nickel deposits are known in Brazil, accounting for about 350 · 106 tons of ore with an average of 1.5% Ni. All are of the lateritic type. These deposits are scattered throughout the country, being rarer in the Northeastern Region and in the South, below 25 °S latitude. They are mainly associated with mafic-ultramafic massifs of large dimensions and ultramafic alkaline complexes, and occur in climatic regions of contrasting seasons. The weathering profile developed over the fresh rock consists, from bottom to top, of the following horizons: altered rock, coarse saprolite, argillaceous saprolite, ferruginous saprolite and lateritic overburden. The thickness of each horizon varies from one deposit to another, the whole profile generally exceeding 20 m. The saprolitic horizons with inherited minerals (serpentine, chlorite) or neoformed minerals (smectites) constitute the silicated nickel ore and are thicker were climatic conditions are drier; the ferruginous upper horizons made up of iron oxide-hydroxides are more developed in more humid regions. In Brazil, the silicated ore generally prevails over the oxidized ore. The main Ni-bearing minerals are serpentine, smectite, garnierite and goethite. The lateritic nickel deposits of Brazil may be correlated with two erosion surfaces, corresponding to the Sul Americano (Lower Tertiary) and Velhas (Upper Tertiary) levelling cycles. The degree of dismantling of the higher and more ancient surface and the consequent development of the Velhas Surface control the position of the nickel accumulation in the landscape. Thus, the deposits may be found either in the lowlands or in the highlands, where they are always covered by a silcrete layer. The alteration profiles in the Brazilian lateritic nickel deposits are broadly similar to those described elsewhere in the world. However, they present two characteristic features: the silicated ore prevails over the oxidized ore, and a silicified layer covers the profies developed on

  16. Brazil's mental health adventure.

    Science.gov (United States)

    Weingarten, Richard

    2003-01-01

    This is an account of my trips to Brazil in 2001 where I worked on a series of mental health projects with Brazilian colleagues. I first got interested in Brazil after I graduated from college when I was a Peace Corps volunteer in Northeast Brazil (Bahia state). After I got out of the Peace Corps I moved to Rio de Janeiro and went to work for United Press International (UPI) in their Rio bureau. I was UPI foreign news correspondent for a year and a half. Those years in Brazil were probably the happiest years of my life. Later on, after I became ill in the U.S., my Brazilian connection played an important role in my recovery. Raised in a Victorian family in a small town in the Midwest, and schooled in a traditional boarding school for boys and then at an all men's college, Brazil's lively Latino culture served as a healthy antidote for my tendency to be reserved and often depressed. My contact with Brazilians and Brazilian culture always beckoned me on. I maintained contact with my friends in Brazil and they stuck by me through my illness years. What seemed like my emotional and intellectual "excess" to me, was easily accepted by my Brazilian friends. I felt much more myself interacting with Brazilians and connected to a larger sense of self I developed in Brazil. I traveled to Brazil at every opportunity and made friends with Brazilians I met in the States. I initiated Portuguese classes at John Carroll University in Cleveland, Ohio in the early 1990s and then was invited to teach Brazilian culture to undergraduates. These appointments and my own resilience moved me past one depression and a dysthymia condition and into the wider community. I regained my confidence as a teacher, a role I had before and during the years of my illness. From this position, I organized a club for Brazilian students studying in the Cleveland area. After this teaching stint, I felt ready to pursue full time employment and began a job search that would eventually land me in New Haven at

  17. Zika virus infections imported from Brazil to Portugal, 2015

    Directory of Open Access Journals (Sweden)

    L. Zé-Zé

    2016-01-01

    Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present.

  18. On the creative economy chain in Brazil: potential and challenges

    OpenAIRE

    ANITA KON

    2016-01-01

    ABSTRACT The article presents an analysis of the Creative Economy in Brazil, showing its development potential for the generation of income and employment, in order to the country's development resumption. They are initially presented concepts and features of the Creative Economy for, in sequence, to analyze the economic development profile and potential of this industry in Brazil. The empirical part introduces some methodological aspects, in continuing with the analysis of the creative chain...

  19. Detecting clusters of mutations.

    Directory of Open Access Journals (Sweden)

    Tong Zhou

    Full Text Available Positive selection for protein function can lead to multiple mutations within a small stretch of DNA, i.e., to a cluster of mutations. Recently, Wagner proposed a method to detect such mutation clusters. His method, however, did not take into account that residues with high solvent accessibility are inherently more variable than residues with low solvent accessibility. Here, we propose a new algorithm to detect clustered evolution. Our algorithm controls for different substitution probabilities at buried and exposed sites in the tertiary protein structure, and uses random permutations to calculate accurate P values for inferred clusters. We apply the algorithm to genomes of bacteria, fly, and mammals, and find several clusters of mutations in functionally important regions of proteins. Surprisingly, clustered evolution is a relatively rare phenomenon. Only between 2% and 10% of the genes we analyze contain a statistically significant mutation cluster. We also find that not controlling for solvent accessibility leads to an excess of clusters in terminal and solvent-exposed regions of proteins. Our algorithm provides a novel method to identify functionally relevant divergence between groups of species. Moreover, it could also be useful to detect artifacts in automatically assembled genomes.

  20. Homozygous mutation in the NPHP3 gene causing foetal nephronophthisis

    DEFF Research Database (Denmark)

    Abdullah, Uzma; Farooq, Muhammad; Fatima, Ambrin

    2017-01-01

    We present a case of a foetal sonographic finding of hyper-echogenic kidneys, which led to a strategic series of genetic tests and identified a homozygous mutation (c.424C > T, p. R142*) in the NPHP3 gene. Our study provides a rare presentation of NPHP3-related ciliopathy and adds to the mutation...

  1. Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Joao Leandro Paula Ferreira

    2013-01-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 transmitted drug resistance (TDR is an important public health issue. In Brazil, low to intermediate resistance levels have been described. We assessed 225 HIV-1 infected, antiretroviral naïve individuals, from HIV Reference Centers at two major metropolitan areas of Sao Paulo (Sao Paulo and Campinas, the state that concentrates most of the Brazilian Aids cases. TDR was analyzed by Stanford Calibrated Population Resistance criteria (CPR, and mutations were observed in 17 individuals (7.6%, 95% CI: 4.5%–11.9%. Seventy-six percent of genomes (13/17 with TDR carried a nonnucleoside reverse transcriptase inhibitor (NNRTI resistance mutation, mostly K103N/S (9/13, 69%, potentially compromising the preferential first-line therapy suggested by the Brazilian HIV Treatment Guideline that recommends efavirenz-based combinations. Moreover, 6/17 (35% had multiple mutations associated with resistance to one or more classes. HIV-1 B was the prevalent subtype (80%; other subtypes include HIV-1 F and C, mosaics BC, BF, and single cases of subtype A1 and CRF02_AG. The HIV Reference Center of Campinas presented more cases with TDR, with a significant association of TDR with clade B infection (P<0.05.

  2. TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal acute myeloid leukemia patients with NPM1+ and FLT3-ITD - mutations.

    Science.gov (United States)

    Tian, Xiaopeng; Xu, Yang; Yin, Jia; Tian, Hong; Chen, Suning; Wu, Depei; Sun, Aining

    2014-07-01

    Cytogenetically normal acute myeloid leukemia (cn-AML) is a group of heterogeneous diseases. Gene mutations are increasingly used to assess the prognosis of cn-AML patients and guide risk-adapted treatment. In the present study, we analyzed the molecular genetics characteristics of 373 adult cn-AML patients and explored the relationship between TET2 gene mutations or different genetic mutation patterns and prognosis. We found that 16.1 % of patients had TET2 mutations, 31.6 % had FLT3 internal tandem duplications (ITDs), 6.2 % had FLT3 tyrosine kinase domain mutations, 2.4 % had c-KIT mutations, 37.8 % had NPM1 mutations, 11.3 % had WT1 mutations, 5.9 % had RUNX1 mutations, 11.5 % had ASXL1 mutations, 3.8 % had MLL-PTDs, 7.8 % had IDH1 mutations, 7.8 % had NRAS mutations, 12.3 % had IDH2 mutations, 1.6 % had EZH2 mutations, and 14.7 % had DNMT3A mutations, while none had CBL mutations. Gene mutations were detected in 76.94 % (287/373) of all patients. In the NPM1m(+) patients, those with TET2 mutations were associated with a shorter median overall survival (OS) as compared to TET2 wild-type (wt) patients (9.9 vs. 27.0 months, respectively; P = 0.023); Interestingly, the TET2 mutation was identified as an unfavorable prognostic factor and was closely associated with a shorter median OS as compared to TET2-wt (9.5 vs. 32.2 months, respectively; P = 0.013) in the NPM1m(+)/FLT3-ITDm(-) patient group. Thus, identification of TET2 combined with classic NPM1 and FLT3-ITD mutations allowed us to stratify cn-AML into distinct subtypes.

  3. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium.

    Science.gov (United States)

    Pillai, Rathi N; Behera, Madhusmita; Berry, Lynne D; Rossi, Mike R; Kris, Mark G; Johnson, Bruce E; Bunn, Paul A; Ramalingam, Suresh S; Khuri, Fadlo R

    2017-11-01

    Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2-directed therapies. A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%-4%). One patient had a concurrent mesenchymal-epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never-smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2-targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy. HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed therapies should be investigated in this subgroup of patients. Cancer 2017;123:4099-4105. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child: evidence for chimerism involving a common mutant founder haplotype: case report.

    Science.gov (United States)

    da Silva, Edaise M; Achatz, Maria Isabel W; Martel-Planche, Ghyslaine; Montagnini, André L; Olivier, Magali; Prolla, Patricia A; Hainaut, Pierre; Soares, Fernando A

    2011-10-17

    Gastric adenocarcinoma is rare in children and adolescents, with about 17 cases under age 21 in the world's literature. We report a case of invasive well-differentiated metastatic gastric cancer in a Brazilian 12-year-old boy without documented familial history of cancer. The patient, diagnosed with metastatic disease, died seven months after surgery. DNA from intra-surgical specimens revealed a TP53 mutation at codon 337 (p.R337H) in samples with neoplastic cells (dysplasia, tumor and metastasis) but not in non-transformed cells (incomplete intestinal metaplasia and non-involved celiac lymph node). In all mutation-positive tissues, p.R337H occurred on the same background, a founder allele identified by a specific haplotype previously described in Brazilian Li-Fraumeni syndrome patients. The same mutant haplotype, corresponding to a founder mutation present in 0.3% of the general population in Southern Brazil, was found in the genome of the father. Presence of this inherited haplotype in the tumor as well as in the father's germline, suggests a rare case of microchimerism in this patient, who may have harbored a small number of mutant cells originating in another individual, perhaps a dizygotic twin that died early in gestation. This case represents one of the earliest ages at diagnosis of gastric cancer ever reported. It shows that cancer inheritance can occur in the absence of an obvious germline mutation, calling for caution in assessing early cancers in populations with common founder mutations such as p.R337H in Southern Brazil.

  5. Homozygous Desmocollin-2 Mutations and Arrhythmogenic Cardiomyopathy.

    Science.gov (United States)

    Lorenzon, Alessandra; Pilichou, Kalliopi; Rigato, Ilaria; Vazza, Giovanni; De Bortoli, Marzia; Calore, Martina; Occhi, Gianluca; Carturan, Elisa; Lazzarini, Elisabetta; Cason, Marco; Mazzotti, Elisa; Poloni, Giulia; Mostacciuolo, Maria Luisa; Daliento, Luciano; Thiene, Gaetano; Corrado, Domenico; Basso, Cristina; Bauce, Barbara; Rampazzo, Alessandra

    2015-10-15

    Dominant mutations in desmocollin-2 (DSC2) gene cause arrhythmogenic cardiomyopathy (ACM), a progressive heart muscle disease characterized by ventricular tachyarrhythmias, heart failure, and risk of juvenile sudden death. Recessive mutations are rare and are associated with a cardiac or cardiocutaneous phenotype. Here, we evaluated the impact of a homozygous founder DSC2 mutation on clinical expression of ACM. An exon-by-exon analysis of the DSC2 coding region was performed in 94 ACM index patients. The c.536A>G (p.D179G) mutation was identified in 5 patients (5.3%), 4 of which resulted to be homozygous carriers. The 5 subjects shared a conserved haplotype, strongly indicating a common founder. Genetic and clinical investigation of probands' families revealed that p.D179G homozygous carriers displayed severe forms of biventricular cardiomyopathy without hair or skin abnormalities. The only heterozygous proband, who carried an additional variant of unknown significance in αT-catenin gene, showed a mild form of ACM without left ventricular involvement. All heterozygous family members were clinically asymptomatic. In conclusion, this is the first homozygous founder mutation in DSC2 gene identified among Italian ACM probands. Our findings provide further evidence of the occurrence of recessive DSC2 mutations in patients with ACM predominantly presenting with biventricular forms of the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The Mutations Associated with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ruti Parvari

    2012-01-01

    Full Text Available Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM. The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in general in genetic studies, the identification of the mutated genes has a direct clinical impact for the families and population involved. Identifying causative mutations immediately amplifies the possibilities for disease prevention through carrier screening and prenatal testing. This often lifts a burden of social isolation from affected families, since healthy family members can be assured of having healthy children. Identification of the mutated genes holds the potential to lead to the understanding of disease etiology, pathophysiology, and therefore potential therapy. This paper presents the genetic variations, or disease-causing mutations, contributing to the pathogenesis of hereditary DCM, and tries to relate these to the functions of the mutated genes.

  7. Apparent directional selection by biased pleiotropic mutation.

    Science.gov (United States)

    Tanaka, Yoshinari

    2010-07-01

    Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

  8. TOX3 mutations in breast cancer.

    Directory of Open Access Journals (Sweden)

    James Owain Jones

    Full Text Available TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe was identified in one tumour (genomic DNA and cDNA. Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.

  9. Portugal, a Brazil Colony

    National Research Council Canada - National Science Library

    Cid, Pedro

    2004-01-01

    ... a new America, in fact, some say that this new vague of migrants towards the terrinha, as Brazilians like to call Portugal, is connected to the strong barriers imposed by the US government, in recent years, to Brazilian citizens willing to enter the United States and to the rippling tide of anti-American feeling in Brazil, right now. Apart from...

  10. Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review.

    Science.gov (United States)

    Ossa, Carlos Andrés; Torres, Diana

    2016-07-01

    Numerous epidemiological factors affect the probability of developing breast or ovarian cancer, but no predictor is as determinant as inheriting a mutation in BRCA1 or BRCA2. The concept of the founder effect explains the reduced genetic variability in some populations, according to the theory that new populations can be formed from a reduced number of individuals, so the new population would carry only a small fraction of the genetic variability of the original population. The main purpose of this review is to provide an update on the state of the art in founder mutations and some recurrent mutations that have recently been described in Latin America. A literature search was performed in the electronic databases of PUBMED, EMBASE, LILACS, and BIREME using the terms BRCA1, BRCA2, founder mutation, Latin American population, and Hispanic. Sixty-two papers were identified, of which 38 were considered relevant for this review. Each result is shown per country. In Latin America, clear founder effects have been reported in Mexico (BRCA1 del exons 9-12), Brazil (BRCA1 5382insC and BRCA2 c.156_157insAlu), and Colombia (BRCA1 3450del4, A1708E, and BRCA2 3034del4) and in Latinas residing in Southern California (BRCA1 185delAG, IVS5+1G>A, S955x, and R1443x). Of these, mutation BRCA1 3450del4 has also been reported in Brazil and Chile, whereas mutation BRCA2 3034del4 has been reported in Argentina and Peru. These data support the idea that although most Hispanic populations are the result of a mixture between Europeans, Africans, and Amerindians, the relative proportion of each genetic component varies throughout the Hispanic populations, making it necessary to identify the mutations characteristic of each population to generate mutation profiles adjusted to each one of them. In Latin American countries, and even among regions of the same country, there is great heterogeneity of ancestors. Therefore, Latinas should not be analyzed like other population groups without taking

  11. Are There Mutator Polymerases?

    Directory of Open Access Journals (Sweden)

    Miguel Garcia-Diaz

    2003-01-01

    Full Text Available DNA polymerases are involved in different cellular events, including genome replication and DNA repair. In the last few years, a large number of novel DNA polymerases have been discovered, and the biochemical analysis of their properties has revealed a long list of intriguing features. Some of these polymerases have a very low fidelity and have been suggested to play mutator roles in different processes, like translesion synthesis or somatic hypermutation. The current view of these processes is reviewed, and the current understanding of DNA polymerases and their role as mutator enzymes is discussed.

  12. A Naturally Occurring hPMS2 Mutation Can Confer a Dominant Negative Mutator Phenotype

    Science.gov (United States)

    Nicolaides, Nicholas C.; Littman, Susan J.; Modrich, Paul; Kinzler, Kenneth W.; Vogelstein, Bert

    1998-01-01

    Defects in mismatch repair (MMR) genes result in a mutator phenotype by inducing microsatellite instability (MI), a characteristic of hereditary nonpolyposis colorectal cancers (HNPCC) and a subset of sporadic colon tumors. Present models describing the mechanism by which germ line mutations in MMR genes predispose kindreds to HNPCC suggest a “two-hit” inactivation of both alleles of a particular MMR gene. Here we present experimental evidence that a nonsense mutation at codon 134 of the hPMS2 gene is sufficient to reduce MMR and induce MI in cells containing a wild-type hPMS2 allele. These results have significant implications for understanding the relationship between mutagenesis and carcinogenesis and the ability to generate mammalian cells with mutator phenotypes. PMID:9488480

  13. Diabetes Care in Brazil.

    Science.gov (United States)

    Coutinho, Walmir F; Silva Júnior, Wellington Santana

    2015-01-01

    The diabetes epidemic affects most countries across the world and is increasing at alarming rates in Latin America. Nearly 12 million individuals have diabetes in Brazil, and the current prevalence ranges from 6.3% to 13.5%, depending on the region and the diagnostic criteria adopted in each study. To provide an overview of diabetes care in Brazil, focusing on studies of diabetes epidemiology, prevalence of patients within the standard targets of care, and economic burden of diabetes and its complications. SciELO and PubMed searches were performed for the terms "diabetes," "Brazil," "Brazilian," and "health system"; relevant literature from 1990 to 2015 was selected. Additional articles identified from reference list searches were also included. All articles selected were published in Portuguese and/or English. Recent studies detected a prevalence of gestational diabetes mellitus of nearly 20%. Among patients with type 1 diabetes, almost 90% fail to reach target of glycemic control, with less than 30% receiving treatment for both hypertension and dyslipidemia. More than 75% of patients with type 2 diabetes are either overweight or obese. Most of these patients fail to reach glycemic targets (42.1%) and less than 30% reached the target for systolic and diastolic blood pressure, body mass index, or low-density lipoprotein cholesterol. Only 0.2% of patients reach all these anthropometric and metabolic targets. Brazil is the fourth country in the world in number of patients with diabetes. Regardless of the diabetes type, the majority of patients do not meet other metabolic control goals. The economic burden of diabetes and its complications in Brazil is extremely high, and more effective approaches for preventions and management are urgently needed. Copyright © 2015. Published by Elsevier Inc.

  14. HIV-1 primary and secondary antiretroviral drug resistance and genetic diversity among pregnant women from central Brazil.

    Science.gov (United States)

    Cardoso, Ludimila Paula Vaz; Pereira, Gisner Alves Souza; Viegas, Angela Alves; Schmaltz, Luiza Emylce Pelá Rosado; Stefani, Mariane Martins de Araújo

    2010-03-01

    Antiretroviral (ARV) resistance mutations in HIV-1 may reduce the efficacy of prophylactic therapy to mother-to-child transmission and impact future treatment options. ARV resistance mutations and HIV-1 phylogenetic diversity in protease (PR) and reverse transcriptase (RT) genes were assessed among 77 pregnant women (35 naïve, 42 treated with ARV) from Goiânia/Goiás, central west Brazil. ARV mutations in PR/RT genes were analyzed against the Stanford Database, PR/RT HIV-1 subtypes were assigned by phylogenetic analysis and env/gag subtypes were identified by heteroduplex mobility analysis (HMA). Naïve patients had accessory mutations in the PR gene [A71T (1/6), L10V (2/6), L10I (3/6)] and in the RT gene [V118I (2/6), V179D (1/6), V106I (1/6), K101Q (1/6), H221Y (1/6)]. Seven patients (16.7%) under ARV presented drug resistance mutations, one of them to three ARV classes. Most isolates (67.5%) were subtype B, 11.7% subtype F1 and 3.9% subtype C. Recombinant B(PR)/F1(RT) viruses represented 10.4% while F1(PR)/B(RT) viruses made up 6.5%. HIV-1 envgag/PRRT genes were identified as 66.2% subtype B, 3.9% subtype C, 6.5% subtype F1 and approximately 25% B and F1 viruses. HIV-1 genetic diversity in envgag/PRRT genes indicates the spread and dissemination of BF1 recombinant viruses among a significant proportion of patients from central west Brazil. Moreover, discovery of HIV-1 secondary resistance among a considerable number of pregnant women under ARV therapy indicates the importance of genotypic testing during pregnancy for optimal prophylactic intervention. J. Med. Virol. 82:351-357, 2010. (c) 2010 Wiley-Liss, Inc.

  15. Nuclear research reactors in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Cota, Anna Paula Leite; Mesquita, Amir Zacarias, E-mail: aplc@cdtn.b, E-mail: amir@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2011-07-01

    The rising concerns about global warming and energy security have spurred a revival of interest in nuclear energy, giving birth to a 'nuclear power renaissance' in several countries in the world. Particularly in Brazil, in the recent years, the nuclear power renaissance can be seen in the actions that comprise its nuclear program, summarily the increase of the investments in nuclear research institutes and the government target to design and build the Brazilian Multipurpose research Reactor (BMR). In the last 50 years, Brazilian research reactors have been used for training, for producing radioisotopes to meet demands in industry and nuclear medicine, for miscellaneous irradiation services and for academic research. Moreover, the research reactors are used as laboratories to develop technologies in power reactors, which are evaluated today at around 450 worldwide. In this application, those reactors become more viable in relation to power reactors by the lowest cost, by the operation at low temperatures and, furthermore, by lower demand for nuclear fuel. In Brazil, four research reactors were installed: the IEA-R1 and the MB-01 reactors, both at the Instituto de Pesquisas Energeticas Nucleares (IPEN, Sao Paulo); the Argonauta, at the Instituto de Engenharia Nuclear (IEN, Rio de Janeiro) and the IPR-R1 TRIGA reactor, at the Centro de Desenvolvimento da Tecnologia Nuclear (CDTN, Belo Horizonte). The present paper intends to enumerate the characteristics of these reactors, their utilization and current academic research. Therefore, through this paper, we intend to collaborate on the BMR project. (author)

  16. The Inherited p53 Mutation in the Brazilian Population.

    Science.gov (United States)

    Achatz, Maria Isabel; Zambetti, Gerard P

    2016-12-01

    A common criticism of studying rare diseases is the often-limited relevance of the findings to human health. Here, we review ∼15 years of research into an unusual germline TP53 mutation (p.R337H) that began with its detection in children with adrenocortical carcinoma (ACC), a remarkably rare childhood cancer that is associated with poor prognosis. We have come to learn that the p.R337H mutation exists at a very high frequency in Southern and Southeastern Brazil, occurring in one of 375 individuals within a total population of ∼100 million. Moreover, it has been determined that carriers of this founder mutation display variable tumor susceptibility, ranging from isolated cases of pediatric ACC to Li-Fraumeni or Li-Fraumeni-like (LFL) syndromes, thus representing a significant medical issue for this country. Studying the biochemical and molecular consequences of this mutation on p53 tumor-suppressor activity, as well as the putative additional genetic alterations that cooperate with this mutation, is advancing our understanding of how p53 functions in tumor suppression in general. These studies, which originated with a rare childhood tumor, are providing important information for guiding genetic counselors and physicians in treating their patients and are already providing clinical benefit. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  17. Factor V Leiden Mutation and PT 20210 Mutation Test

    Science.gov (United States)

    ... Patient Resources For Health Professionals Subscribe Search Factor V Leiden Mutation and PT 20210 Mutation Send Us ... As Activated Protein C Resistance APC Resistance Factor V R506Q PT G20210A Factor II 20210 Factor II ...

  18. Molecular evaluation of a novel missense mutation & an insertional truncating mutation in SUMF1 gene

    Directory of Open Access Journals (Sweden)

    Udhaya H Kotecha

    2014-01-01

    Full Text Available Background & objectives: Multiple suphphatase deficiency (MSD is an autosomal recessive disorder affecting the post translational activation of all enzymes of the sulphatase family. To date, approximately 30 different mutations have been identified in the causative gene, sulfatase modifying factor 1 (SUMF1. We describe here the mutation analysis of a case of MSD. Methods: The proband was a four year old boy with developmental delay followed by neuroregression. He had coarse facies, appendicular hypertonia, truncal ataxia and ichthyosis limited to both lower limbs. Radiographs showed dysostosis multiplex. Clinical suspicion of MSD was confirmed by enzyme analysis of four enzymes of the sulphatase group. Results: The patient was compound heterozygote for a c.451A>G (p.K151E substitution in exon 3 and a single base insertion mutation (c.690_691 InsT in exon 5 in the SUMF1 gene. The bioinformatic analysis of the missense mutation revealed no apparent effect on the overall structure. However, the mutated 151-amino acid residue was found to be adjacent to the substrate binding and the active site residues, thereby affecting the substrate binding and/or catalytic activity, resulting in almost complete loss of enzyme function. Conclusions: The two mutations identified in the present case were novel. This is perhaps the first report of an insertion mutation in SUMF1 causing premature truncation of the protein.

  19. Molecular evaluation of a novel missense mutation & an insertional truncating mutation in SUMF1 gene.

    Science.gov (United States)

    Kotecha, Udhaya H; Movva, Sireesha; Sharma, Deepak; Verma, Jyotsna; Puri, Ratna Dua; Verma, Ishwar Chander

    2014-07-01

    Multiple suphphatase deficiency (MSD) is an autosomal recessive disorder affecting the post translational activation of all enzymes of the sulphatase family. To date, approximately 30 different mutations have been identified in the causative gene, sulfatase modifying factor 1 (SUMF1). We describe here the mutation analysis of a case of MSD. The proband was a four year old boy with developmental delay followed by neuroregression. He had coarse facies, appendicular hypertonia, truncal ataxia and ichthyosis limited to both lower limbs. Radiographs showed dysostosis multiplex. Clinical suspicion of MSD was confirmed by enzyme analysis of four enzymes of the sulphatase group. The patient was compound heterozygote for a c.451A>G (p.K151E) substitution in exon 3 and a single base insertion mutation (c.690_691 InsT) in exon 5 in the SUMF1 gene. The bioinformatic analysis of the missense mutation revealed no apparent effect on the overall structure. However, the mutated 151-amino acid residue was found to be adjacent to the substrate binding and the active site residues, thereby affecting the substrate binding and/or catalytic activity, resulting in almost complete loss of enzyme function. The two mutations identified in the present case were novel. This is perhaps the first report of an insertion mutation in SUMF1 causing premature truncation of the protein.

  20. Msx1 Mutations

    Science.gov (United States)

    Wang, Y.; Kong, H.; Mues, G.; D’Souza, R.

    2011-01-01

    Mutations in the transcription factors PAX9 and MSX1 cause selective tooth agenesis in humans. In tooth bud mesenchyme of mice, both proteins are required for the expression of Bmp4, which is the key signaling factor for progression to the next step of tooth development. We have previously shown that Pax9 can transactivate a 2.4-kb Bmp4 promoter construct, and that most tooth-agenesis-causing PAX9 mutations impair DNA binding and Bmp4 promoter activation. We also found that Msx1 by itself represses transcription from this proximal Bmp4 promoter, and that, in combination with Pax9, it acts as a potentiator of Pax9-induced Bmp4 transactivation. This synergism of Msx1 with Pax9 is significant, because it is currently the only documented mechanism for Msx1-mediated activation of Bmp4. In this study, we investigated whether the 5 known tooth-agenesis-causing MSX1 missense mutations disrupt this Pax9-potentiation effect, or if they lead to deficiencies in protein stability, protein-protein interactions, nuclear translocation, and DNA-binding. We found that none of the studied molecular mechanisms yielded a satisfactory explanation for the pathogenic effects of the Msx1 mutations, calling for an entirely different approach to the investigation of this step of odontogenesis on the molecular level. PMID:21297014

  1. Presentation Presentación = Presentation

    Directory of Open Access Journals (Sweden)

    Leany BARREIRO LEMOS

    2011-01-01

    Full Text Available This issue of América Latina Hoy is dedicated to the evaluation of the first year of government of Luiz Inacio Lula da Silva in Brazil.Este número de América Latina Hoy está dedicado a la evaluación del primer año de gobierno de Luiz Inácio Lula da Silva en Brasil.

  2. Mutations in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Reichardt, J.K.V. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States)

    1995-10-01

    This Letter raises four issues concerning two papers on galactosemia published in the March 1995 of the Journal. First, table 2 in the paper by Elsas et al. incorrectly attributes seven galactose-l-phosphate uridyl transferase (GALT) mutations (S135L, L195P, K285N, N314D, R333W, R333G, and K334R). The table also fails to mention that others have reported the same two findings attributed to {open_quotes}Leslie et al.; Elsas et al. and in press{close_quotes} and {open_quotes}Leslie et al.; Elsas et al.{close_quotes} The first finding on the prevalence of the Q188R galactosemia mutation in the G/G Caucasian population has also been described by Ng et al., and the second finding on the correlation of the N314D GALT mutation with the Duarte variant was reported by Lin et al. Second, Elsas et al. suggest that the E203K and N314D mutations may {open_quotes}produce intra-allelic complementation when in cis{close_quotes}. This speculation is supported by the activity data of individual III-2 but is inconsistent with the activities of three other individuals I-1, II-1, and III-1 of the same pedigree. The GALT activity measured in these three individuals suggests a dominant negative effect of E203K in E203K-N314D chromosomes, since they all have less than normal activity. Thus, the preponderance of the data in this paper is at odds with the authors speculation. It is worth recalling that Lin et al. also identified four N314D GALT mutations on 95 galactosemic chromosomes examined. A similar situation also appears to be the case in proband III-1 (with genotype E203K-N314D/IVSC) in the Elsas et al. paper. 9 refs.

  3. Case studies in international tobacco surveillance: cigarette smuggling in Brazil.

    Science.gov (United States)

    Shafey, O; Cokkinides, V; Cavalcante, T M; Teixeira, M; Vianna, C; Thun, M

    2002-09-01

    This article is the first in a series of international case studies developed by the American Cancer Society to illustrate use of publicly available surveillance data for regional tobacco control. A descriptive analysis of Brazil and Paraguay cigarette production and trade data from official sources. Per capita cigarette consumption for Brazil and its neighbour was calculated from 1970 to 1998 using data on production, imports, and exports from NATIONS, the National Tobacco Information Online System. A 63% decrease was observed in the estimate of per capita consumption of cigarettes in Brazil between 1986 and 1998 (from 1913 cigarettes per person in 1986 to 714 cigarettes per person in 1998) and a 16-fold increase in Paraguay was observed during the same period (from 678 cigarettes per person in 1986 to 10 929 cigarettes per person in 1998). Following Brazil's 1999 passage of a 150% cigarette export tax, cigarette exports fell 89% and Brazil's estimated per capita consumption rose to 1990 levels (based on preliminary data). Per capita consumption in Paraguay also fell to 1990 levels. These trends coincide with local evidence that large volumes of cigarettes manufactured in Brazil for export to Paraguay are smuggled back and consumed as tax-free contraband in Brazil. It is hoped that this case study will draw wider public attention to the problems that smuggling presents for tobacco control, help identify other countries confronting similar issues, and stimulate effective interventions.

  4. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

    Science.gov (United States)

    Nangalia, J; Massie, C E; Baxter, E J; Nice, F L; Gundem, G; Wedge, D C; Avezov, E; Li, J; Kollmann, K; Kent, D G; Aziz, A; Godfrey, A L; Hinton, J; Martincorena, I; Van Loo, P; Jones, A V; Guglielmelli, P; Tarpey, P; Harding, H P; Fitzpatrick, J D; Goudie, C T; Ortmann, C A; Loughran, S J; Raine, K; Jones, D R; Butler, A P; Teague, J W; O'Meara, S; McLaren, S; Bianchi, M; Silber, Y; Dimitropoulou, D; Bloxham, D; Mudie, L; Maddison, M; Robinson, B; Keohane, C; Maclean, C; Hill, K; Orchard, K; Tauro, S; Du, M-Q; Greaves, M; Bowen, D; Huntly, B J P; Harrison, C N; Cross, N C P; Ron, D; Vannucchi, A M; Papaemmanuil, E; Campbell, P J; Green, A R

    2013-12-19

    Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2. (Funded by the Kay

  5. High-throughput Phenotyping of Lung Cancer Somatic Mutations.

    Science.gov (United States)

    Berger, Alice H; Brooks, Angela N; Wu, Xiaoyun; Shrestha, Yashaswi; Chouinard, Candace; Piccioni, Federica; Bagul, Mukta; Kamburov, Atanas; Imielinski, Marcin; Hogstrom, Larson; Zhu, Cong; Yang, Xiaoping; Pantel, Sasha; Sakai, Ryo; Watson, Jacqueline; Kaplan, Nathan; Campbell, Joshua D; Singh, Shantanu; Root, David E; Narayan, Rajiv; Natoli, Ted; Lahr, David L; Tirosh, Itay; Tamayo, Pablo; Getz, Gad; Wong, Bang; Doench, John; Subramanian, Aravind; Golub, Todd R; Meyerson, Matthew; Boehm, Jesse S

    2016-08-08

    Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Analysis of HIV-1 protease gene reveals frequent multiple infections followed by recombination among drug treated individuals living in Sao Paulo and Santos, Brazil.

    Directory of Open Access Journals (Sweden)

    Edsel Renata De Morais Nunes

    Full Text Available The present study investigated the prevalence of HIV-1 multiple infections in a population composed by 47 patients under HAART failure and enrolled at the National DST/AIDS, Program, Ministry of Health, Brazil.Detection of multiple infections was done using a previously published RFLP assay for the HIV-1 protease gene, which is able of distinguishing between infections caused by a single or multiple HIV-1 subtypes. Samples with multiple infections were cloned, and sequence data submitted to phylogenetic analysis. We were able to identify 17 HIV-1 multiple infections out of 47 samples. Multiple infections were mostly composed by a mixture of recombinant viruses (94%, with only one case in which protease gene pure subtypes B and F were recovered. This is the first study that reports the prevalence of multiple infections and intersubtype recombinants in a population undergoing HAART in Brazil. Based on the data there was a steep increase of multiple infections after the introduction of the combined antiretroviral therapy in Brazil. Cases of multiple infections may be associated with HIV-1 genetic diversity through recombination allowing for the generation of viruses showing a combination of resistance mutations.

  7. Norovirus Recombinant Strains Isolated from Gastroenteritis Outbreaks in Southern Brazil, 2004-2011.

    Science.gov (United States)

    Fumian, Tulio Machado; da Silva Ribeiro de Andrade, Juliana; Leite, José Paulo Gagliardi; Miagostovich, Marize Pereira

    2016-01-01

    Noroviruses are recognized as one of the leading causes of viral acute gastroenteritis, responsible for almost 50% of acute gastroenteritis outbreaks worldwide. The positive single-strand RNA genome of noroviruses presents a high mutation rate and these viruses are constantly evolving by nucleotide mutation and genome recombination. Norovirus recombinant strains have been detected as causing acute gastroenteritis outbreaks in several countries. However, in Brazil, only one report of a norovirus recombinant strain (GII.P7/GII.20) has been described in the northern region so far. For this study, 38 norovirus strains representative of outbreaks, 11 GII.4 and 27 non-GII.4, were randomly selected and amplified at the ORF1/ORF2 junction. Genetic recombination was identified by constructing phylogenetic trees of the polymerase and capsid genes, and further SimPlot and Bootscan analysis of the ORF1/ORF2 overlap. Sequence analysis revealed that 23 out of 27 (85%) non-GII.4 noroviruses were recombinant strains, characterized as: GII.P7/GII.6 (n = 9); GIIP.g/GII.12 (n = 4); GII.P16/GII.3 (n = 4); GII.Pe/GII.17 (n = 2); GII.P7/GII.14 (n = 1); GII.P13/GII.17 (n = 1); GII.P21/GII.3 (n = 1); and GII.P21/GII.13 (n = 1). On the other hand, among the GII.4 variants analyzed (Den Haag_2006b and New Orleans_2009) no recombination was observed. These data revealed the great diversity of norovirus recombinant strains associated with outbreaks, and describe for the first time these recombinant types circulating in Brazil. Our results obtained in southern Brazil corroborate the previous report for the northern region, demonstrating that norovirus recombinant strains are circulating more frequently than we expected. In addition, these results emphasize the relevance of including ORF1/ORF2-based analysis in surveillance studies as well as the importance of characterizing strains from other Brazilian regions to obtain epidemiological data for norovirus recombinant strains circulating in the

  8. Norovirus Recombinant Strains Isolated from Gastroenteritis Outbreaks in Southern Brazil, 2004-2011.

    Directory of Open Access Journals (Sweden)

    Tulio Machado Fumian

    Full Text Available Noroviruses are recognized as one of the leading causes of viral acute gastroenteritis, responsible for almost 50% of acute gastroenteritis outbreaks worldwide. The positive single-strand RNA genome of noroviruses presents a high mutation rate and these viruses are constantly evolving by nucleotide mutation and genome recombination. Norovirus recombinant strains have been detected as causing acute gastroenteritis outbreaks in several countries. However, in Brazil, only one report of a norovirus recombinant strain (GII.P7/GII.20 has been described in the northern region so far. For this study, 38 norovirus strains representative of outbreaks, 11 GII.4 and 27 non-GII.4, were randomly selected and amplified at the ORF1/ORF2 junction. Genetic recombination was identified by constructing phylogenetic trees of the polymerase and capsid genes, and further SimPlot and Bootscan analysis of the ORF1/ORF2 overlap. Sequence analysis revealed that 23 out of 27 (85% non-GII.4 noroviruses were recombinant strains, characterized as: GII.P7/GII.6 (n = 9; GIIP.g/GII.12 (n = 4; GII.P16/GII.3 (n = 4; GII.Pe/GII.17 (n = 2; GII.P7/GII.14 (n = 1; GII.P13/GII.17 (n = 1; GII.P21/GII.3 (n = 1; and GII.P21/GII.13 (n = 1. On the other hand, among the GII.4 variants analyzed (Den Haag_2006b and New Orleans_2009 no recombination was observed. These data revealed the great diversity of norovirus recombinant strains associated with outbreaks, and describe for the first time these recombinant types circulating in Brazil. Our results obtained in southern Brazil corroborate the previous report for the northern region, demonstrating that norovirus recombinant strains are circulating more frequently than we expected. In addition, these results emphasize the relevance of including ORF1/ORF2-based analysis in surveillance studies as well as the importance of characterizing strains from other Brazilian regions to obtain epidemiological data for norovirus recombinant strains

  9. A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome.

    Science.gov (United States)

    Estephan, Eduardo de Paula; Sobreira, Cláudia Ferreira da Rosa; Dos Santos, André Clériston José; Tomaselli, Pedro José; Marques, Wilson; Ortega, Roberta Paiva Magalhães; Costa, Marcela Câmara Machado; da Silva, André Macedo Serafim; Mendonça, Rodrigo Holanda; Caldas, Vitor Marques; Zambon, Antonio Alberto; Abath Neto, Osório; Marchiori, Paulo Eurípedes; Heise, Carlos Otto; Reed, Umbertina Conti; Azuma, Yoshiteru; Töpf, Ana; Lochmüller, Hanns; Zanoteli, Edmar

    2018-01-30

    The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.

  10. Chloride Channel ClCN7 Mutations Are Responsible for Severe Recessive, Dominant, and Intermediate Osteopetrosis

    National Research Council Canada - National Science Library

    Frattini, Annalisa; Pangrazio, Alessandra; Susani, Lucia; Sobacchi, Cristina; Mirolo, Massimiliano; Abinun, Mario; Andolina, Marino; Flanagan, Adrienne; Horwitz, Edwin M; Mihci, Ercan; Notarangelo, Luigi D; Ramenghi, Ugo; Teti, Anna; Van Hove, Johan; Vujic, Dragana; Young, Terri; Albertini, Alberto; Orchard, Paul J; Vezzoni, Paolo; Villa, Anna

    2003-01-01

    Among 94 osteopetrotic patients presenting with a severe clinical picture and diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them had the expected two recessive mutations...

  11. Mutation supply and the repeatability of selection for antibiotic resistance

    Science.gov (United States)

    van Dijk, Thomas; Hwang, Sungmin; Krug, Joachim; de Visser, J. Arjan G. M.; Zwart, Mark P.

    2017-10-01

    Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution, which is a necessary condition for predictability. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of antibiotic resistance gene TEM-1 β-lactamase in Escherichia coli, generated by error-prone PCR, were subjected to different antibiotic concentrations. We determined whether populations went extinct or survived, and sequenced the TEM gene of the surviving populations. The distribution of mutations per allele in our mutant libraries followed a Poisson distribution. Extinction patterns could be explained by a simple stochastic model that assumed the sampling of beneficial mutations was key for survival. In most surviving populations, alleles containing at least one known large-effect beneficial mutation were present. These genotype data also support a model which only invokes sampling effects to describe the occurrence of alleles containing large-effect driver mutations. Hence, evolution is largely predictable given cursory knowledge of mutational fitness effects, the mutation rate and population size. There were no clear trends in the repeatability of selected mutants when we considered all mutations present. However, when only known large-effect mutations were considered, the outcome of selection is less repeatable for large libraries, in contrast to expectations. We show experimentally that alleles carrying multiple mutations selected from large libraries confer higher resistance levels relative to alleles with only a known large-effect mutation, suggesting that the scarcity of high-resistance alleles carrying multiple mutations may contribute to the decrease in repeatability at large library sizes.

  12. Innovation Policies of Brazil

    Science.gov (United States)

    2013-09-01

    and Embraer (aircraft manufacture), and private multinational companies include Vale (mining), Volkswagen do Brasil (automotive and biofuels...innovation. The high cost of doing business in Brazil known as custo Brasil is a barrier to starting and growing new businesses and arises from high...Exterior, MDIC) 1960 Responsible for policy development of industry, trade and services National Bank for Economic and Social Development ( Banco

  13. STYLISTICS IN BRAZIL

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Falcão Uchôa

    2015-11-01

    Full Text Available This article aims at pointing out the origins and the evolution of Stylistics in Brazil. After an introduction about the emergence, in Europe, of Stylistics as a discipline in the field of language studies, the article concerns itself with the contributions of Philology, Linguistics, the Theory of Literature and Grammar to the study of the most different stylistic devices employed by writers, particularly by Brazilian ones.

  14. Comprehensive Mutation Analysis in Colorectal Flat Adenomas

    Science.gov (United States)

    Voorham, Quirinus J. M.; Carvalho, Beatriz; Spiertz, Angela J.; Claes, Bart; Mongera, Sandra; van Grieken, Nicole C. T.; Grabsch, Heike; Kliment, Martin; Rembacken, Bjorn; van de Wiel, Mark A.; Quirke, Philip; Mulder, Chris J. J.; Lambrechts, Diether; van Engeland, Manon; Meijer, Gerrit A.

    2012-01-01

    Background Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes. Methods A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in “hot spot” regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (β-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing. Results APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes. Conclusion The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway. PMID:22848674

  15. The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, S.J.; Gladwin, A.J.; Dixon, M.J. [Univ. of Manchester (United Kingdom)

    1997-03-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mutations, which are spread throughout the gene, are presented. This brings the total reported to date to 35, which represents a detection rate of 60%. Of the mutations that have been reported to date, all but one result in the introduction of a premature-termination codon into the predicted protein, treacle. Moreover, the mutations are largely family specific, although a common 5-bp deletion in exon 24 (seven different families) and a recurrent splicing mutation in intron 3 (two different families) have been identified. This mutational spectrum supports the hypothesis that TCS results from haploin-sufficiency. 49 refs., 4 figs., 3 tabs.

  16. Schistosomiasis control in Brazil

    Directory of Open Access Journals (Sweden)

    Katz Naftale

    1998-01-01

    Full Text Available In 1975 the Special Programme for Schistosomiasis Control was introduced in Brazil with the objective of controlling this parasitic disease in six northeastern states. The methodology applied varied largely from state to state, but was based mainly on chemotherapy, This Programme was modified about ten years after it beginning with the main goals including control of morbidity and the blockage of establishment of new foci in non-endemic areas. In two states, Bahia and Minas Gerais, the schistosomiasis control programme started in 1979 and 1983, respectively. The recently made evaluation of those two programmes is the main focus of this paper. It must also be pointed out, that the great majority of the studies performed by different researchers in Brazil, at different endemic areas, consistently found significant decrease on prevalence and incidence, when control measures are repeatedly used for several years. Significant decrease of hepatosplenic forms in the studied areas is well documented in Brazil. After more than 20 years of schistosomiasis control programmes in our country, chemotherapy has shown to be a very important tool for the control of morbidity and to decrease prevalence and incidence in endemic areas. Nevertheless, in medium and long terms, sanitation, water supply, sewage draining and health education seem to be the real tools when the aim is persistent and definitive schistosomiasis control.

  17. Radiopharmacy education in Brazil

    Directory of Open Access Journals (Sweden)

    Ralph Santos-Oliveira

    2014-01-01

    Full Text Available The number of schools of pharmacy has been increasing each year in Brazil. From 2002 to 2013 over 300 new schools were opened in Brazil with a final number of 415 schools of pharmacy in operation around the country. Of these schools, only 28 schools offer a course in radiopharmacy (7.77%. However, the demand for such trained professionals has grown exponentially in Brazil, especially following amendment 49 (February 2006 that broke the monopoly on the production, distribution, and marketing of short half-life radiopharmaceuticals, and the recent constitutional amendment project 517/2010, which was approved in the last instance and is waiting for final approval by the President. Thus, in this scenario, there are a total of 417 radiopharmacy services across the country waiting for qualified professionals to fill posts. However, while there are insufficient trained professionals, radiopharmacy services under the aegis of Agencia Nacional de Vigilancia Sanitaria - Brazilian Health Surveillance Agency allow biomedical scientists and biologists to perform specialized functions as developed in radiopharmacy services without the presence of radiopharmacists.

  18. Health promotion in Brazil.

    Science.gov (United States)

    Ivo de Carvalho, Antonio; Westphal, Marcia Faria; Pereira Lima, Vera Lucia Góes

    2007-01-01

    Brazil, a Latin American country of continental proportions and contrasts, demographic inequalities, and social inequities, concomitantly faces the challenge of preventing and controlling infectious diseases, injuries, and non-communicable diseases. The loss of strength of the biomedical paradigm, the change in epidemiological profile, and the sociopolitical and cultural challenges of recent decades have fostered the emergence of new formulations about public health thinking and practice. Among them, are the paradigms of Brazilian Collective Health and Health Promotion. The former provides philosophical support for Brazil's Unified Health System (SUS). The aim of this article is to discuss the development of public health within the country's history, and to analyze and compare the theoretical assumptions of Health Promotion and Collective Health. We conclude that health promotion, based on the principles and values disseminated by the international Charters and concerned with social actors and social determinants of the health-disease process, has significant potential to promote the improvement of living and health conditions of the population. This frame of reference guided the formulation of the National Policy of Health Promotion within the Unified Health System, which was institutionalized by a ministerial decree. The importance and application of evaluating the effectiveness of health promotion processes and methodologies in Brazil have been guided by various frames of reference, which we clarify in this article through describing historical processes.

  19. The cardiac phenotype in patients with a CHD7 mutation

    DEFF Research Database (Denmark)

    Corsten-Janssen, Nicole; Kerstjens-Frederikse, Wilhelmina S; du Marchie Sarvaas, Gideon J

    2013-01-01

    . Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7...

  20. Mutations in the AGXT2L2 gene cause phosphohydroxylysinuria

    NARCIS (Netherlands)

    Veiga-da-Cunha, Maria; Verhoeven-Duif, Nanda M; de Koning, Tom J; Duran, Marinus; Dorland, Bert; Van Schaftingen, Emile

    2013-01-01

    Phosphohydroxylysinuria has been described in two patients with neurological symptoms, but the deficient enzyme or mutated gene has never been identified. In the present work, we tested the hypothesis that this condition is due to mutations in the AGXT2L2 gene, recently shown to encode

  1. reverse transcriptase inhibitors drug resistance mutations in drug ...

    African Journals Online (AJOL)

    2011-01-01

    Jan 1, 2011 ... REVERSE TRANSCRIPTASE INHIBITORS DRUG RESISTANCE MUTATIONS IN DRUG-NAIVE HIV TYPE 1 POSITIVE ... S. A. Khamadi, BSc, MSc, PhD, Senior Research Scientist, Centre for Virus Research, Kenya Medical Research Institute, ... NNRTI associated resistance mutations were present.

  2. Timing of de novo mutations - relevance to health and disease

    NARCIS (Netherlands)

    Acuna Hidalgo, R.

    2017-01-01

    The work presented in this thesis shows that mutations arise constantly, between one generation and the next but also throughout life. This continuous occurrence of mutations leads to extraordinary genetic diversity between individuals but is also at the origin of the existence of genetically

  3. Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer.

    Science.gov (United States)

    Grellety, Thomas; Gros, Audrey; Pedeutour, Florence; Merlio, Jean-Philippe; Duranton-Tanneur, Valerie; Italiano, Antoine; Soubeyran, Isabelle

    2016-10-01

    Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications.

  4. [Botany and phytotherapy in Brazil].

    Science.gov (United States)

    Plumel, M M

    1990-01-01

    After a general survey of botanical exploration in Amazonia in the past and a summary of the present situation, an account is given of the work carried out in the field and the herbarium is search of plant species of potential therapeutic interest. The potential resources of these vast forests are far from being completely explored and still contain a number of unstudied species. Despite the low probability of major discoveries in this field, a promising approach involves the rational collection of data on traditional medicine, the precise identification of species utilized, and the scientific evaluation of their true properties. As an example, a short list of plants commonly utilized for folk medicine in Amazonia and north-eastern Brazil illustrates the importance of phytotherapy for peoples often deprived of other therapeutic means.

  5. Mutation update for the PORCN gene

    DEFF Research Database (Denmark)

    Lombardi, Maria Paola; Bulk, Saskia; Celli, Jacopo

    2011-01-01

    variants and allows the inclusion of future reports. The database is based on the Leiden Open (source) Variation Database (LOVD) software, and is accessible online at http://www.lovd.nl/porcn. At present, the database contains 106 variants, representing 68 different mutations, scattered along the whole...

  6. Kin Selection - Mutation Balance

    DEFF Research Database (Denmark)

    Dyken, J. David Van; Linksvayer, Timothy Arnold; Wade, Michael J.

    2011-01-01

    Abstract Social conflict, in the form of intraspecific selfish "cheating" has been observed in a number of natural systems. However, a formal, evolutionary genetic theory of social cheating that provides an explanatory, predictive framework for these observations is lacking. Here we derive the kin...... selection-mutation balance, which provides an evolutionary null hypothesis for the statics and dynamics of cheating. When social interactions have linear fitness effects and Hamilton´s rule is satisfied, selection is never strong enough to eliminate recurrent cheater mutants from a population, but cheater...... lineages are transient and do not invade. Instead, cheating lineages are eliminated by kin selection but are constantly reintroduced by mutation, maintaining a stable equilibrium frequency of cheaters. The presence of cheaters at equilibrium creates a "cheater load" that selects for mechanisms of cheater...

  7. Studies of human mutation rates

    Energy Technology Data Exchange (ETDEWEB)

    Neel, J.V.

    1990-01-01

    November 1989, marked the beginning of a new three-year cycle of DOE grant support, in connection with which the program underwent a major reorganization. This document presents the progress on the three objectives of the present program which are: to isolate by the technique of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), proteins of special interest because of the relative mutability of the corresponding gene, establish the identity of the protein, and, for selected proteins, move to a characterization of the corresponding gene; to develop a more efficient approach, based on 2-D PAGE, for the detection of variants in DNA, with special reference to the identification of mutations in the parents of the individual whose DNA is being examined; and, to continue an effective interface with the genetic studies on the children of atomic bomb survivors in Japan, with reference to both the planning and implementation of new studies at the molecular level.

  8. Demand for fisheries products in Brazil

    Directory of Open Access Journals (Sweden)

    Daniel Yokoyama Sonoda

    2012-10-01

    Full Text Available Fish consumption per capita in Brazil is relatively modest when compared to other animal proteins. This study analyses the influence of protein prices, other food prices and population income on the fish demand in Brazil. First, the problem of fish supply in Brazil is characterized. It is followed by reviews of the relevant economic theory and methods of Almost Ideal Demand System - AIDS and their elasticity calculations. A descriptive analysis of fish demand in Brazil using the microdata called "Pesquisa de Orçamento Familiar" (Familiar Budget Research - POF 2002-2003 is presented. Finally, demand functions and their elasticities are calculated for two different cases: one considering five groups of animal proteins (Chicken; Milk and Eggs; Fish; Processed Proteins and Red Meat and other with seven groups of food categories (Cereals; Vegetables and Fruits; Milky and Eggs; Oils and Condiments; Fish; Other processed foods; and Meats. The main results are: per capita consumption of fish (4.6 kg per inhabitant per year is low in Brazil because few households consume fish. When only households with fish consumption are considered, the per capita consumption would be higher: 27.2 kg per inhabitant per year. The fish consumption in the North-East Region is concentrated in the low-income class. In the Center-South Region, the fish consumption is lower and concentrated in the intermediate income classes. The main substitutes for fish are the processed proteins and not the traditional types of meat, such as chicken and red meat.

  9. Expanding CEP290 mutational spectrum in ciliopathies.

    Science.gov (United States)

    Travaglini, Lorena; Brancati, Francesco; Attie-Bitach, Tania; Audollent, Sophie; Bertini, Enrico; Kaplan, Josseline; Perrault, Isabelle; Iannicelli, Miriam; Mancuso, Brunella; Rigoli, Luciana; Rozet, Jean-Michel; Swistun, Dominika; Tolentino, Jerlyn; Dallapiccola, Bruno; Gleeson, Joseph G; Valente, Enza Maria; Zankl, A; Leventer, R; Grattan-Smith, P; Janecke, A; D'Hooghe, M; Sznajer, Y; Van Coster, R; Demerleir, L; Dias, K; Moco, C; Moreira, A; Kim, C Ae; Maegawa, G; Petkovic, D; Abdel-Salam, G M H; Abdel-Aleem, A; Zaki, M S; Marti, I; Quijano-Roy, S; Sigaudy, S; de Lonlay, P; Romano, S; Touraine, R; Koenig, M; Lagier-Tourenne, C; Messer, J; Collignon, P; Wolf, N; Philippi, H; Kitsiou Tzeli, S; Halldorsson, S; Johannsdottir, J; Ludvigsson, P; Phadke, S R; Udani, V; Stuart, B; Magee, A; Lev, D; Michelson, M; Ben-Zeev, B; Fischetto, R; Benedicenti, F; Stanzial, F; Borgatti, R; Accorsi, P; Battaglia, S; Fazzi, E; Giordano, L; Pinelli, L; Boccone, L; Bigoni, S; Ferlini, A; Donati, M A; Caridi, G; Divizia, M T; Faravelli, F; Ghiggeri, G; Pessagno, A; Briguglio, M; Briuglia, S; Salpietro, C D; Tortorella, G; Adami, A; Castorina, P; Lalatta, F; Marra, G; Riva, D; Scelsa, B; Spaccini, L; Uziel, G; Del Giudice, E; Laverda, A M; Ludwig, K; Permunian, A; Suppiej, A; Signorini, S; Uggetti, C; Battini, R; Di Giacomo, M; Cilio, M R; Di Sabato, M L; Leuzzi, V; Parisi, P; Pollazzon, M; Silengo, M; De Vescovi, R; Greco, D; Romano, C; Cazzagon, M; Simonati, A; Al-Tawari, A A; Bastaki, L; Mégarbané, A; Sabolic Avramovska, V; de Jong, M M; Stromme, P; Koul, R; Rajab, A; Azam, M; Barbot, C; Martorell Sampol, L; Rodriguez, B; Pascual-Castroviejo, I; Teber, S; Anlar, B; Comu, S; Karaca, E; Kayserili, H; Yüksel, A; Akcakus, M; Al Gazali, L; Sztriha, L; Nicholl, D; Woods, C G; Bennett, C; Hurst, J; Sheridan, E; Barnicoat, A; Hennekam, R; Lees, M; Blair, E; Bernes, S; Sanchez, H; Clark, A E; DeMarco, E; Donahue, C; Sherr, E; Hahn, J; Sanger, T D; Gallager, T E; Dobyns, W B; Daugherty, C; Krishnamoorthy, K S; Sarco, D; Walsh, C A; McKanna, T; Milisa, J; Chung, W K; De Vivo, D C; Raynes, H; Schubert, R; Seward, A; Brooks, D G; Goldstein, A; Caldwell, J; Finsecke, E; Maria, B L; Holden, K; Cruse, R P; Swoboda, K J; Viskochil, D

    2009-10-01

    Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.

  10. BRAF mutation in hairy cell leukemia

    Directory of Open Access Journals (Sweden)

    Ahmad Ahmadzadeh

    2014-09-01

    Full Text Available BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated protein kinase (MAPK signaling pathway. A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL. BRAF V600E is the most common mutation reported in exon15 of BRAF, which is observed in almost all cases of classic HCL, but it is negative in other B-cell malignancies, including the HCL variant. Therefore it can be used as a marker to differentiate between these B-cell disorders. We also discuss the interaction between miRNAs and signaling pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF protein inhibitors may represent an effective treatment. In this review we have evaluated the role of the mutation of the BRAF gene in the pathogenesis and progression of HCL.

  11. Mutation induction in synchronous hamster cells

    Energy Technology Data Exchange (ETDEWEB)

    Aebersold, P.M.

    1975-11-01

    Mutagenesis of synchronous Mutahinese hamster cells by 5-bromodeoxyuridine (BUdR) shows pronounced cell cycle dependency. Resistance to 6-thioguanine (6-TG) and ouabain are induced maximally by BUdR at different times early in the DNA synthesis period, suggesting that the genes coding for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and the (Na/sup +/K/sup +/)-associated ATPase of the plasma membrane are replicated early in the DNA synthesis period. Although BUdR induces mutations in specific genes only when present during their replication, the rate of mutation induction is not linearly related to the amount of BUdR incorporated into DNA. The data show a BUdR concentration threshold for mutation induction, suggesting that BUdR exerts some deterimental allosteric effect on DNA synthesis enzymes.

  12. Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

    Science.gov (United States)

    Mardis, Elaine R.; Ding, Li; Dooling, David J.; Larson, David E.; McLellan, Michael D.; Chen, Ken; Koboldt, Daniel C.; Fulton, Robert S.; Delehaunty, Kim D.; McGrath, Sean D.; Fulton, Lucinda A.; Locke, Devin P.; Magrini, Vincent J.; Abbott, Rachel M.; Vickery, Tammi L.; Reed, Jerry S.; Robinson, Jody S.; Wylie, Todd; Smith, Scott M.; Carmichael, Lynn; Eldred, James M.; Harris, Christopher C.; Walker, Jason; Peck, Joshua B.; Du, Feiyu; Dukes, Adam F.; Sanderson, Gabriel E.; Brummett, Anthony M.; Clark, Eric; McMichael, Joshua F.; Meyer, Rick J.; Schindler, Jonathan K.; Pohl, Craig S.; Wallis, John W.; Shi, Xiaoqi; Lin, Ling; Schmidt, Heather; Tang, Yuzhu; Haipek, Carrie; Wiechert, Madeline E.; Ivy, Jolynda V.; Kalicki, Joelle; Elliott, Glendoria; Ries, Rhonda E.; Payton, Jacqueline E.; Westervelt, Peter; Tomasson, Michael H.; Watson, Mark A.; Baty, Jack; Heath, Sharon; Shannon, William D.; Nagarajan, Rakesh; Link, Daniel C.; Walter, Matthew J.; Graubert, Timothy A.; DiPersio, John F.; Wilson, Richard K.; Ley, Timothy J.

    2011-01-01

    BACKGROUND The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known. METHODS We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome. RESULTS We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis. CONCLUSIONS By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis. PMID:19657110

  13. Imagined futures, present lives

    DEFF Research Database (Denmark)

    Dalsgaard, Anne Line; Wildermuth, Norbert

    2006-01-01

    The article is focused thematically on the uses and meanings of media for (some) young people in Recife, a million-inhabitant city in the northeast of Brazil. The article brings together the perspective of Anne Line Dalsgaard, a long-term anthropological field researcher who is familiar with the ......The article is focused thematically on the uses and meanings of media for (some) young people in Recife, a million-inhabitant city in the northeast of Brazil. The article brings together the perspective of Anne Line Dalsgaard, a long-term anthropological field researcher who is familiar...

  14. Septin mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Elias T Spiliotis

    2016-11-01

    Full Text Available Septins are GTP-binding proteins that are evolutionarily and structurally related to the RAS oncogenes. Septin expression levels are altered in many cancers and new advances point to how abnormal septin expression may contribute to the progression of cancer. In contrast to the RAS GTPases, which are frequently mutated and actively promote tumorigenesis, little is known about the occurrence and role of septin mutations in human cancers. Here, we review septin missense mutations that are currently in the Catalog of Somatic Mutations in Cancer (COSMIC database. The majority of septin mutations occur in tumors of the large intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in SEPT2, SEPT4 and SEPT9 belong to large intestine tumors. From all septins, SEPT9 and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large intestine cancers. While septin mutations occur with frequencies lower than 3%, recurring mutations in several invariant and highly conserved amino acids are found across different septin paralogs and tumor types. Interestingly, a significant number of these mutations occur in the GTP-binding pocket and septin dimerization interfaces. Future studies may determine how these somatic mutations affect septin structure and function, whether they contribute to the progression of specific cancers and if they could serve as tumor-specific biomarkers.

  15. Labour Market Inequality in Brazil and India: A Comparative Brazil ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Labour Market Inequality in Brazil and India: A Comparative Brazil, Russia, India and China (BRIC) Study ... and the Institute for Human Development in Delhi who will develop comparable measures of inequality in wage income and examine contributing factors such as ... Centro Brasileiro de Analise e Planejamento.

  16. Homeschooling in Brazil: A Matter of Rights or a Political Debate?

    Science.gov (United States)

    Barbosa, Luciane Muniz Ribeiro

    2016-01-01

    This article presents an analysis of the right to education in Brazil in light of the growing number of Brazilian families practicing homeschooling. The debate is recent in Brazil. Here we present an analysis of international literature on homeschooling, Brazilian literature on the right to education, and an appraisal of lawsuits against Brazilian…

  17. Workers, Education, and Social Change in Brazil

    Directory of Open Access Journals (Sweden)

    William J. Mello

    2013-09-01

    Full Text Available This article examines how Brazilian labor organizations developed educational programs that simultaneously confronted the issues of large scale illiteracy, particularly among young workers, while at the same time seized the opportunity to educate new generations of social movement and labor activists. Specifically, it explores the educational program Projeto Integrar, organized by the National Confederation of Metalworkers (CNM/CUT, and its importance for the broader process of political transformation presently underway in Brazil.

  18. Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.

    Science.gov (United States)

    Murua Escobar, Hugo; Günther, Kathrin; Richter, Andreas; Soller, Jan T; Winkler, Susanne; Nolte, Ingo; Bullerdiek, Jörn

    2004-01-01

    Point mutations within ras proto-oncogenes, particularly within the mutational hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and in different types of experimentally-induced tumours in animals. So far little is known about ras mutations in naturally occurring canine fibrosarcomas or K-ras mutations in canine melanomas. To elucidate whether ras mutations exist in these naturally occurring tumours in dogs, in the present study we screened 13 canine fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot-spots, making this the first study to investigate a large number of canine fibrosarcomas. None of the samples showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras mutations at the hot-spot loci are very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine tumours investigated.

  19. Systematic analysis of somatic mutations impacting gene expression in 12 tumour types

    Science.gov (United States)

    Ding, Jiarui; McConechy, Melissa K.; Horlings, Hugo M.; Ha, Gavin; Chun Chan, Fong; Funnell, Tyler; Mullaly, Sarah C.; Reimand, Jüri; Bashashati, Ali; Bader, Gary D.; Huntsman, David; Aparicio, Samuel; Condon, Anne; Shah, Sohrab P.

    2015-01-01

    We present a novel hierarchical Bayes statistical model, xseq, to systematically quantify the impact of somatic mutations on expression profiles. We establish the theoretical framework and robust inference characteristics of the method using computational benchmarking. We then use xseq to analyse thousands of tumour data sets available through The Cancer Genome Atlas, to systematically quantify somatic mutations impacting expression profiles. We identify 30 novel cis-effect tumour suppressor gene candidates, enriched in loss-of-function mutations and biallelic inactivation. Analysis of trans-effects of mutations and copy number alterations with xseq identifies mutations in 150 genes impacting expression networks, with 89 novel predictions. We reveal two important novel characteristics of mutation impact on expression: (1) patients harbouring known driver mutations exhibit different downstream gene expression consequences; (2) expression patterns for some mutations are stable across tumour types. These results have critical implications for identification and interpretation of mutations with consequent impact on transcription in cancer. PMID:26436532

  20. Germline mutations of TP53 gene in breast cancer.

    Science.gov (United States)

    Damineni, Surekha; Rao, Vadlamudi Raghavendra; Kumar, Satish; Ravuri, Rajasekar Reddy; Kagitha, Sailaja; Dunna, Nageswara Rao; Digumarthi, Raghunadharao; Satti, Vishnupriya

    2014-09-01

    Germline alterations of the TP53 gene encoding the p53 protein have been observed in the majority of families with the Li-Fraumeni syndrome, a rare dominantly inherited disorder with breast cancer. Genomic DNA samples of 182 breast cancer cases and 186 controls were sequenced for TP53 mutations in the exon 5-9 and intervening introns 5, 7-9. Direct sequencing was done using Applied Biosystem 3730 DNA analyzer. In the present study, we observed nine mutations in the sequenced region, of which five were novel. Hardy-Weinberg equilibrium (HWE) was done for all the mutations; C14181T, T14201G, and G13203A have shown deviation from HWE. High linkage disequilibrium (LD) was observed between C14181T (rs129547788) and T14201G (rs12951053) (r (2) = 0.98.3; D' = 1.00), whereas other observed mutations do not show strong LD with any of the other mutations. None of the intronic mutations has shown significant association with the breast cancer, two exonic mutations G13203A (rs28934578) and A14572G are significantly (P = 0.04, P = 0.007) associated with breast cancer. Germline mutations observed in DNA-binding domain of the gene showed significant association with breast cancer. This study reports five novel germline mutations in the TP53 gene out of which one mutation may confer significant risk to the breast cancer. Mutations in DNA-binding domain of TP53 gene may play role in the early onset and prognosis of breast cancer. The population-based studies of germline mutations in DNA-binding domain of TP53 gene helps in identification of individuals and families who are at risk of developing cancers.

  1. Mutational landscape and significance across 12 major cancer types

    Science.gov (United States)

    Vandin, Fabio; Ye, Kai; Niu, Beifang; Lu, Charles; Xie, Mingchao; Zhang, Qunyuan; McMichael, Joshua F.; Wyczalkowski, Matthew A.; Leiserson, Mark D. M.; Miller, Christopher A.; Welch, John S.; Walter, Matthew J.; Wendl, Michael C.; Ley, Timothy J.; Wilson, Richard K.; Raphael, Benjamin J.; Ding, Li

    2014-01-01

    The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data and analytical results for point mutations and small insertions/deletions from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort. We illustrate the distributions of mutation frequencies, types and contexts across tumour types, and establish their links to tissues of origin, environmental/carcinogen influences, and DNA repair defects. Using the integrated data sets, we identified 127 significantly mutated genes from well-known(forexample, mitogen-activatedprotein kinase, phosphatidylinositol-3-OH kinase,Wnt/β-catenin and receptor tyrosine kinase signalling pathways, and cell cycle control) and emerging (for example, histone, histone modification, splicing, metabolism and proteolysis) cellular processes in cancer. The average number of mutations in these significantly mutated genes varies across tumour types; most tumours have two to six, indicating that the numberof driver mutations required during oncogenesis is relatively small. Mutations in transcriptional factors/regulators show tissue specificity, whereas histone modifiers are often mutated across several cancer types. Clinical association analysis identifies genes having a significant effect on survival, and investigations of mutations with respect to clonal/subclonal architecture delineate their temporal orders during tumorigenesis. Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment. PMID:24132290

  2. Calreticulin Mutations in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Noa Lavi

    2014-10-01

    Full Text Available With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph− myeloproliferative neoplasms (MPNs in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET and primary myelofibrosis (PMF. At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations and recurrent 5-bp insertions (type 2 mutations in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review.

  3. Zika virus infection in a traveller returning to Europe from Brazil, March 2015.

    Science.gov (United States)

    Zammarchi, L; Tappe, D; Fortuna, C; Remoli, M E; Günther, S; Venturi, G; Bartoloni, A; Schmidt-Chanasit, J

    2015-06-11

    We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present.

  4. Scanning insights on sustainability and supply chain management in Brazil

    Directory of Open Access Journals (Sweden)

    Minelle E. Silva

    2017-08-01

    Full Text Available This paper aims to analyse how the publications in Brazil are considering the relationship between sustainability and supply chain management. For this end, a literature review was carried out in 120 Brazilian academic journals in which 124 papers were identified, from 2008 until 2013. When considering the Triple Bottom Line approach, the results show that sustainability research in Brazil is focusing on the environmental dimension and SCM research is focusing on the economic dimension. Additional inputs are provided by integrating the governance dimension in the analysis to underline which actions and policies are discussed in Brazil at a corporate level. To support the results a consultation of experts in the field of sustainability in Brazil was fulfilled, and three case examples are presented to explain some of the research results. The findings on publications in Brazil contrast with international studies, particularly on the topic of social performance and management in supply chains. One of the main conclusions is that there are large opportunities to increase publications about sustainability and SCM in the country and that Brazil presents some specificities in the field that researchers and managers shall consider.

  5. The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yuji Mishima

    2017-04-01

    Full Text Available The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs is prognostic in multiple myeloma (MM, but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.

  6. ENG mutational mosaicism in a family with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Kjeldsen, Anette D; Ousager, Lilian Bomme

    2018-01-01

    BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder caused by mutations in ENG, ACVRL1, or SMAD4. Around 90% of HHT patients present with a heterozygous pathogenic genetic variation. Almost all cases of HHT have a family history. Very few cases are de......, and the flanking sequences of the genes were sequenced by NGS. RESULTS: The proband had clinical HHT fulfilling the Curaçao criteria and genetic testing identified a frameshift mutation in ENG. The mother of the proband, also with clinical HHT, was found negative when analyzing DNA from blood for the familial...... mutation using Sanger sequencing. Analyzing her DNA by NGS HHT panel sequencing when extracted from both peripheral blood leukocytes, and cheek swabs, identified the familial ENG mutation at low levels. CONCLUSION: We provide evidence of ENG mutational mosaicism in an individual presenting with clinical...

  7. Mutation analysis in Norwegian families with hereditary hemorrhagic telangiectasia: founder mutations in ACVRL1.

    Science.gov (United States)

    Heimdal, K; Dalhus, B; Rødningen, O K; Kroken, M; Eiklid, K; Dheyauldeen, S; Røysland, T; Andersen, R; Kulseth, M A

    2016-02-01

    Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is an autosomal dominant inherited disease defined by the presence of epistaxis and mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in internal organs. In most families (~85%), HHT is caused by mutations in the ENG (HHT1) or the ACVRL1 (HHT2) genes. Here, we report the results of genetic testing of 113 Norwegian families with suspected or definite HHT. Variants in ENG and ACVRL1 were found in 105 families (42 ENG, 63 ACVRL1), including six novel variants of uncertain pathogenic significance. Mutation types were similar to previous reports with more missense variants in ACVRL1 and more nonsense, frameshift and splice-site mutations in ENG. Thirty-two variants were novel in this study. The preponderance of ACVRL1 mutations was due to founder mutations, specifically, c.830C>A (p.Thr277Lys), which was found in 24 families from the same geographical area of Norway. We discuss the importance of founder mutations and present a thorough evaluation of missense and splice-site variants. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Detection of Ultra-Rare Mitochondrial Mutations in Breast Stem Cells by Duplex Sequencing.

    Directory of Open Access Journals (Sweden)

    Eun Hyun Ahn

    Full Text Available Long-lived adult stem cells could accumulate non-repaired DNA damage or mutations that increase the risk of tumor formation. To date, studies on mutations in stem cells have concentrated on clonal (homoplasmic mutations and have not focused on rarely occurring stochastic mutations that may accumulate during stem cell dormancy. A major challenge in investigating these rare mutations is that conventional next generation sequencing (NGS methods have high error rates. We have established a new method termed Duplex Sequencing (DS, which detects mutations with unprecedented accuracy. We present a comprehensive analysis of mitochondrial DNA mutations in human breast normal stem cells and non-stem cells using DS. The vast majority of mutations occur at low frequency and are not detectable by NGS. The most prevalent point mutation types are the C>T/G>A and A>G/T>C transitions. The mutations exhibit a strand bias with higher prevalence of G>A, T>C, and A>C mutations on the light strand of the mitochondrial genome. The overall rare mutation frequency is significantly lower in stem cells than in the corresponding non-stem cells. We have identified common and unique non-homoplasmic mutations between non-stem and stem cells that include new mutations which have not been reported previously. Four mutations found within the MT-ND5 gene (m.12684G>A, m.12705C>T, m.13095T>C, m.13105A>G are present in all groups of stem and non-stem cells. Two mutations (m.8567T>C, m.10547C>G are found only in non-stem cells. This first genome-wide analysis of mitochondrial DNA mutations may aid in characterizing human breast normal epithelial cells and serve as a reference for cancer stem cell mutation profiles.

  9. Detection of Ultra-Rare Mitochondrial Mutations in Breast Stem Cells by Duplex Sequencing

    Science.gov (United States)

    Ahn, Eun Hyun; Hirohata, Kensen; Kohrn, Brendan F.; Fox, Edward J.; Chang, Chia-Cheng; Loeb, Lawrence A.

    2015-01-01

    Long-lived adult stem cells could accumulate non-repaired DNA damage or mutations that increase the risk of tumor formation. To date, studies on mutations in stem cells have concentrated on clonal (homoplasmic) mutations and have not focused on rarely occurring stochastic mutations that may accumulate during stem cell dormancy. A major challenge in investigating these rare mutations is that conventional next generation sequencing (NGS) methods have high error rates. We have established a new method termed Duplex Sequencing (DS), which detects mutations with unprecedented accuracy. We present a comprehensive analysis of mitochondrial DNA mutations in human breast normal stem cells and non-stem cells using DS. The vast majority of mutations occur at low frequency and are not detectable by NGS. The most prevalent point mutation types are the C>T/G>A and A>G/T>C transitions. The mutations exhibit a strand bias with higher prevalence of G>A, T>C, and A>C mutations on the light strand of the mitochondrial genome. The overall rare mutation frequency is significantly lower in stem cells than in the corresponding non-stem cells. We have identified common and unique non-homoplasmic mutations between non-stem and stem cells that include new mutations which have not been reported previously. Four mutations found within the MT-ND5 gene (m.12684G>A, m.12705C>T, m.13095T>C, m.13105A>G) are present in all groups of stem and non-stem cells. Two mutations (m.8567T>C, m.10547C>G) are found only in non-stem cells. This first genome-wide analysis of mitochondrial DNA mutations may aid in characterizing human breast normal epithelial cells and serve as a reference for cancer stem cell mutation profiles. PMID:26305705

  10. Establishment and cryptic transmission of Zika virus in Brazil and the Americas

    Science.gov (United States)

    Faria, N. R.; Quick, J.; Claro, I. M.; Thézé, J.; de Jesus, J. G.; Giovanetti, M.; Kraemer, M. U. G.; Hill, S. C.; Black, A.; da Costa, A. C.; Franco, L. C.; Silva, S. P.; Wu, C.-H.; Raghwani, J.; Cauchemez, S.; Du Plessis, L.; Verotti, M. P.; de Oliveira, W. K.; Carmo, E. H.; Coelho, G. E.; Santelli, A. C. F. S.; Vinhal, L. C.; Henriques, C. M.; Simpson, J. T.; Loose, M.; Andersen, K. G.; Grubaugh, N. D.; Somasekar, S.; Chiu, C. Y.; Muñoz-Medina, J. E.; Gonzalez-Bonilla, C. R.; Arias, C. F.; Lewis-Ximenez, L. L.; Baylis, S. A.; Chieppe, A. O.; Aguiar, S. F.; Fernandes, C. A.; Lemos, P. S.; Nascimento, B. L. S.; Monteiro, H. A. O.; Siqueira, I. C.; de Queiroz, M. G.; de Souza, T. R.; Bezerra, J. F.; Lemos, M. R.; Pereira, G. F.; Loudal, D.; Moura, L. C.; Dhalia, R.; França, R. F.; Magalhães, T.; Marques, E. T.; Jaenisch, T.; Wallau, G. L.; de Lima, M. C.; Nascimento, V.; de Cerqueira, E. M.; de Lima, M. M.; Mascarenhas, D. L.; Neto, J. P. Moura; Levin, A. S.; Tozetto-Mendoza, T. R.; Fonseca, S. N.; Mendes-Correa, M. C.; Milagres, F. P.; Segurado, A.; Holmes, E. C.; Rambaut, A.; Bedford, T.; Nunes, M. R. T.; Sabino, E. C.; Alcantara, L. C. J.; Loman, N. J.; Pybus, O. G.

    2017-06-01

    Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

  11. Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

    Science.gov (United States)

    Faria, N R; Quick, J; Claro, I M; Thézé, J; de Jesus, J G; Giovanetti, M; Kraemer, M U G; Hill, S C; Black, A; da Costa, A C; Franco, L C; Silva, S P; Wu, C-H; Raghwani, J; Cauchemez, S; du Plessis, L; Verotti, M P; de Oliveira, W K; Carmo, E H; Coelho, G E; Santelli, A C F S; Vinhal, L C; Henriques, C M; Simpson, J T; Loose, M; Andersen, K G; Grubaugh, N D; Somasekar, S; Chiu, C Y; Muñoz-Medina, J E; Gonzalez-Bonilla, C R; Arias, C F; Lewis-Ximenez, L L; Baylis, S A; Chieppe, A O; Aguiar, S F; Fernandes, C A; Lemos, P S; Nascimento, B L S; Monteiro, H A O; Siqueira, I C; de Queiroz, M G; de Souza, T R; Bezerra, J F; Lemos, M R; Pereira, G F; Loudal, D; Moura, L C; Dhalia, R; França, R F; Magalhães, T; Marques, E T; Jaenisch, T; Wallau, G L; de Lima, M C; Nascimento, V; de Cerqueira, E M; de Lima, M M; Mascarenhas, D L; Neto, J P Moura; Levin, A S; Tozetto-Mendoza, T R; Fonseca, S N; Mendes-Correa, M C; Milagres, F P; Segurado, A; Holmes, E C; Rambaut, A; Bedford, T; Nunes, M R T; Sabino, E C; Alcantara, L C J; Loman, N J; Pybus, O G

    2017-06-15

    Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

  12. Danish wind power in Brazil. Part 1. The future of wind power in Brazil - market analysis

    Energy Technology Data Exchange (ETDEWEB)

    Husted Rich, N.

    1996-04-01

    More than 95% of total energy produced in Brazil comes from highly efficient hydroelectric power plants but, faced with a serious shortage of energy after the year 2000, the country is now considering wind energy as one of the basic alternatives for energy supply. It is suggested that biomass, wind energy and biogas may be included in a future supply policy for the north-east region of the land. The structure of, the privatisation, legislation and the tariff system within the Brazilian power sector are described in addition to the present situation regarding wind energy in the country, including current and coming projects in this field, the excellent wind conditions in Northeastern Brazil and investment possibilities. The political activities in this field of the Danish Folkecenter for Renewable Energy are noted and future developments in Brazil are discussed. It is concluded that there are good prospects for Danish windmill technology on the Brazilian market. Wind measurement programs are presently being carried out in various areas of the country, though a number of impediments to the development of wind energy in Brazil remain. (AB)

  13. Germ-line origins of mutation in families with hemophilia B: The sex ratio varies with the type of mutation

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.; Bottema, C.D.K.; Schaid, D.J.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States)); Cohen, M.P. (Vanderbilt Univ., Nashville, TN (United States)); Sexauer, C.L. (Children' s Hospital, Oklahoma City, OK (United States))

    1993-01-01

    Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, the authors report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by them, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males. 62 refs., 1 fig., 5 tabs.

  14. One third of Danish hypertrophic cardiomyopathy patients with MYH7 mutations have mutations [corrected] in MYH7 rod region.

    Science.gov (United States)

    Hougs, Lotte; Havndrup, Ole; Bundgaard, Henning; Køber, Lars; Vuust, Jens; Larsen, Lars Allan; Christiansen, Michael; Andersen, Paal Skytt

    2005-02-01

    Familial hypertrophic cardiomyopathy (FHC) is, in most cases, a disease of the sarcomere, caused by a mutation in one of 10 known sarcomere disease genes. More than 266 mutations have been identified since 1989. The FHC disease gene first characterized MYH7, encodes the cardiac beta-myosin heavy chain, and contains more than 115 of these mutations. However, in most studies, only the region encoding the globular head and the hinge region of the mature cardiac beta-myosin heavy chain have been investigated. Furthermore, most studies carries out screening for mutations in the most prevalent disease genes, and discontinues screening when an apparent disease-associated mutation has been identified. The aim of the present study was to screen for mutations in the rod region of the MYH7 gene in all probands of the cohort, regardless of the known genetic status of the proband. Three disease-causing mutations were identified in the rod region in four probands using capillary electrophoresis single-strand conformation polymorphism as a screening method. All mutations were novel: N1327K, R1712W, and E1753K. Two of the probands had already been shown to carry other FHC-associated mutations. In conclusion, we show that in the Danish cohort we find one third of all MYH7 mutations in the rod-encoding region and we find that two of the patients carrying these mutations also carry mutations in other FHC disease genes stressing the need for a complete screening of all known disease genes in FHC-patients.

  15. HFE gene mutations and iron status of Brazilian blood donors

    Directory of Open Access Journals (Sweden)

    P.C.J.L. Santos

    2010-01-01

    Full Text Available Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542 were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21% increase (P = 0.018 and a 83.65% decrease (P = 0.007 in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91%, P = 0.001 and the HFE 63HD plus DD genotype (55.84%, P = 0.021. In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner.

  16. Upward Lightning in Brazil

    Science.gov (United States)

    Schumann, C.; Saba, M. M.; Alves, J.; Warner, T. A.; Albrecht, R. I.; Bie, L. L.

    2012-12-01

    Observations of upward lightning from tall objects have been reported since 1939. Interest in this subject has grown recently, some of it because of the rapid expansion of wind power generation. Also, with the increasing number of tall buildings and towers, there will be a corresponding increase in the number of upward lightning flashes from these structures. Reports from recent field observations are beginning to address the nature of upward lightning initiation, but much still needs to be learned. Examples are studies of upward lightning from towers in winter thunderstorms in Japan (Wang and Takagi, 2010; and Lu et al., 2009) and summer thunderstorms in Europe (Miki et al., 2005; Flache et al., 2008; and Diendorfer et al., 2009; Zhou et al., 2011) and in North America (Mazur and Ruhnke, 2011; Hussein et al., 2011; Warner, 2011, and Warner et al., 2011). Up to January 2012, no upward flash had ever been registered in Brazil. With the help of some video cameras, we recorded 15 upward lightning which started from one of the towers located on Peak Jaraguá in the city of São Paulo. This paper describes the first results of this field campaign. A combination of high-speed video and standard definition video were used to record upward lightning flashes from multiple towers in Sao Paulo, Brazil, a city located in southeastern Brazil with a population over 10 million people, an average elevation of around 800 meters above sea level, and a flash density of 15 flashes/km2/year. Observations of 15 upward flashes made with these assets were analyzed along with BrasilDAT Lightning Detection Network and a lightning mapping array (LMA) and electric field sensors.

  17. Exome mutation burden predicts clinical outcome in ovarian cancer carrying mutated BRCA1 and BRCA2 genes

    DEFF Research Database (Denmark)

    Birkbak, Nicolai Juul; Kochupurakkal, Bose; Gonzalez-Izarzugaza, Jose Maria

    2013-01-01

    Reliable biomarkers predicting resistance or sensitivity to anti-cancer therapy are critical for oncologists to select proper therapeutic drugs in individual cancer patients. Ovarian and breast cancer patients carrying germline mutations in BRCA1 or BRCA2 genes are often sensitive to DNA damaging...... drugs and relative to non-mutation carriers present a favorable clinical outcome following therapy. Genome sequencing studies have shown a high number of mutations in the tumor genome in patients carrying BRCA1 or BRCA2 mutations (mBRCA). The present study used exome-sequencing and SNP 6 array data...... had either germlines or somatic mutations of BRCA1 or BRCA2 genes. The results revealed that the Nmut was significantly lower in the chemotherapy-resistant mBRCA HGSOC defined by progression within 6 months after completion of first line platinum-based chemotherapy. We found a significant association...

  18. Towards linked open gene mutations data

    Science.gov (United States)

    2012-01-01

    Background With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework. In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data. Methods A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest. Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite. Results We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application. Conclusions This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development. The publication of variation information as Linked Data opens new perspectives

  19. Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31

    Directory of Open Access Journals (Sweden)

    Epplen Joerg T

    2008-07-01

    Full Text Available Abstract Background Mutations in the SPG4 gene (spastin and in the SPG3A gene (atlastin account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP. Recently, mutations in the REEP1 gene were identified to cause autosomal dominant HSP type SPG31. The purpose of this study was to determine the prevalence of REEP1 mutations in a cohort of 162 unrelated Caucasian index patients with 'pure' HSP and a positive family history (at least two persons per family presented symptoms. Methods 162 patients were screened for mutations by, both, DHPLC and direct sequencing. Results Ten mutations were identified in the REEP1 gene, these included eight novel mutations comprising small insertions/deletions causing frame shifts and subsequently premature stop codons, one nonsense mutation and one splice site mutation as well as two missense mutations. Both missense mutations and the splice site mutation were not identified in 170 control subjects. Conclusion In our HSP cohort we found pathogenic mutations in 4.3% of cases with autosomal dominant inheritance. Our results confirm the previously observed mutation range of 3% to 6.5%, respectively, and they widen the spectrum of REEP1 mutations.

  20. Social Psychotherapy in Brazil.

    Science.gov (United States)

    Fleury, Heloisa J; Marra, Marlene M; Knobel, Anna M

    2015-10-01

    This paper describes the practice of sociodrama, a method created by J. L. Moreno in the 1930s, and the Brazilian contemporary socio-psychodrama. In 1970, after the Fifth International Congress of Psychodrama was held in Brazil, group psychotherapy began to flourish both in private practice and hospital clinical settings. Twenty years later, the Brazilian health care system added group work as a reimbursable mental health procedure to improve social health policies. In this context, socio-psychodrama became a key resource for social health promotion within groups. Some specific conceptual contributions by Brazilians on sociodrama are also noteworthy.

  1. Coccidia of gallinaceous meat birds in Brazil

    Directory of Open Access Journals (Sweden)

    Marcel Teixeira

    Full Text Available Coccidiosis is a disease that limits the production and marketing of gallinaceous birds in North America, especially quails, pheasants and chukar partridges. Virtually no research has been conducted in South America on the causative agents of diseases among these birds, including coccidia. The aim of this work was to make first observations on Eimeria spp. in the chukar partridge Alectoris chukar and the grey quail Coturnix coturnix, which are reared for meat in Brazil. Fecal and tissue samples were collected from commercial farms and were examined for oocysts, gross and microscopic lesions or endogenous stages. From this examination, it was found that partridges raised in Brazil did not have any visible infection. However, grey quails presented mild infection and two Eimeria species that had previously been described in other birds were identified.

  2. Coccidia of gallinaceous meat birds in Brazil.

    Science.gov (United States)

    Teixeira, Marcel; Melo, Antônio Diego Brandão; Albuquerque, George Rego; Rocha, Patrícia Tironi; Monteiro, Jomar Patrício

    2015-01-01

    Coccidiosis is a disease that limits the production and marketing of gallinaceous birds in North America, especially quails, pheasants and chukar partridges. Virtually no research has been conducted in South America on the causative agents of diseases among these birds, including coccidia. The aim of this work was to make first observations on Eimeria spp. in the chukar partridge Alectoris chukar and the grey quail Coturnix coturnix, which are reared for meat in Brazil. Fecal and tissue samples were collected from commercial farms and were examined for oocysts, gross and microscopic lesions or endogenous stages. From this examination, it was found that partridges raised in Brazil did not have any visible infection. However, grey quails presented mild infection and two Eimeria species that had previously been described in other birds were identified.

  3. Genetic diversity of noroviruses in Brazil

    Directory of Open Access Journals (Sweden)

    Julia Monassa Fioretti

    2011-12-01

    Full Text Available Norovirus (NoV infections are a major cause of acute gastroenteritis outbreaks around the world. In Brazil, the surveillance system for acute diarrhoea does not include the diagnosis of NoV, precluding the ability to assess its impact on public health. The present study assessed the circulation of NoV genotypes in different Brazilian states by partial nucleotide sequencing analysis of the genomic region coding for the major capsid viral protein. NoV genogroup II genotype 4 (GII.4 was the prevalent (78% followed by GII.6, GII.7, GII.12, GII.16 and GII.17, demonstrating the great diversity of NoV genotypes circulating in Brazil. Thus, this paper highlights the importance of a virological surveillance system to detect and characterize emerging strains of NoV and their spreading potential.

  4. Investing in Private Equity in Brazil

    Directory of Open Access Journals (Sweden)

    Antônio Marcos Duarte Junior

    2016-01-01

    Full Text Available ABSTRACT We consider the problem of selecting private equity funds for investment in Brazil. The proposed methodology is based on multi-criteria decision-making. Real data obtained from one of the largest pension funds in Brazil is used to illustrate a practical application of the methodology when selecting investments among eleven private equity funds available in the local financial market. The multi-criteria method TOPSIS is adopted with a total of twenty two criteria to order the investment alternatives. A sensitivity analysis is also presented. The methodology proposed allows a standardized decision-making process, facilitating the process of selecting private equity funds for investment in Brazilian financial markets.

  5. The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers

    NARCIS (Netherlands)

    Rijken, J. A.; Niemeijer, N. D.; Jonker, M. A.; Eijkelenkamp, K.; Jansen, J. C.; van Berkel, A.; Timmers, H. J. L. M.; Kunst, H. P. M.; Bisschop, P. H. L. T.; Kerstens, M. N.; Dreijerink, K. M. A.; van Dooren, M. F.; van der Horst-Schrivers, A. N. A.; Hes, F. J.; Leemans, C. R.; Corssmit, E. P. M.; Hensen, E. F.

    Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers

  6. The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers

    NARCIS (Netherlands)

    Rijken, J. A.; Niemeijer, N. D.; Jonker, M. A.; Eijkelenkamp, K.; Jansen, J. C.; van Berkel, A.; Timmers, H. J. L. M.; Kunst, H. P. M.; Bisschop, P. H. L. T.; Kerstens, M. N.; Dreijerink, K. M. A.; van Dooren, M. F.; van der Horst-Schrivers, A. N. A.; Hes, F. J.; Leemans, C. R.; Corssmit, E. P. M.; Hensen, E. F.

    2018-01-01

    Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers

  7. Molecular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in The Netherlands

    NARCIS (Netherlands)

    Lombardi, M. P.; Redeker, E. J.; Defesche, J. C.; Kamerling, S. W.; Trip, M. D.; Mannens, M. M.; Havekes, L. M.; Kastelein, J. J.

    2000-01-01

    Mutations in the LDL receptor are responsible for familial hypercholesterolemia (FH). At present, more than 600 mutations of the LDL receptor gene are known to underlie FH. However, the array of mutations varies considerably in different populations. Therefore, the delineation of essentially all LDL

  8. Plantas aquáticas e nível de infestação das espécies presentes no reservatório de Bariri, no Rio Tietê Aquatic plants and infestation level at the Bariri reservoir in Tietê River, Brazil

    Directory of Open Access Journals (Sweden)

    F.T. Carvalho

    2005-06-01

    Full Text Available O monitoramento da vegetação aquática permite avaliar a evolução das comunidades e determinar o potencial de danos associados a essas populações. O objetivo do trabalho foi identificar as plantas aquáticas e os níveis de infestação de cada espécie, presentes no reservatório de Bariri. Foram avaliados todos os focos de vegetação aquática presente na represa (194 pontos, e os pontos foram demarcados com um aparelho de GPS. As plantas foram identificadas e realizou-se uma estimativa visual do valor geográfico do ponto (tamanho da área e a distribuição proporcional das plantas no foco de infestação. Foram encontradas 15 espécies de plantas aquáticas vegetando na represa de Bariri. Considerando que as principais espécies ocorreram com níveis de infestação acima de 10%, as mais importantes foram: Brachiaria mutica (27,0% da área e 97,4% de freqüência, B. subquadripara (22,7% da área e 96,9% de freqüência, Eichhornia crassipes (13,8% da área e 85,6% de freqüência e Typha angustifolia (16,7% da área e 72,7% de freqüência. Outra espécie que pode ser destacada e que apresentou um bom potencial de infestação foi Enidra sessilis, que ocorreu em 8,9% de ocupação na área vegetada e com 76,3% de freqüência.Aquatic vegetation monitoring allows to evaluate community evolution and to determine the potential of damages associated to these populations. The objective of this work was to identify the aquatic plants and infestation levels of each species in the Bariri reservoir in the state of São Paulo, Brazil. All the aquatic vegetation foci in the dam (194 points were evaluated and marked with GPS equipment. The plants were identified and a visual estimate of the geographic value of the point (size of the area and a proportional distribution of the plants in the focus were carried out. Fifteen macrophyte species were found vegetating in the Bariri dam. Due to the great diversity of the species found, those presenting

  9. Mental health economics: insights from Brazil.

    Science.gov (United States)

    Cruz, Luciane; Lima, Ana Flavia Da Silva; Graeff-Martins, Ana; Maia, Carlos Renato Moreira; Ziegelmann, Patricia; Miguel, Sandoro; Fleck, Marcelo; Polanczyk, Carisi

    2013-04-01

    As the responsibility and demand on health care grows and resources do not increase at the same pace, the healthcare system has been forced to reconsider the benefits and costs of their actions, to ensure a rational and effective decision-making process regarding the adoption of interventions and allocation of resources. Cost-effectiveness (CE) studies represent one of the basic tools to achieve this goal. To present the current state of Health Technology Assessment (HTA) and health economics in mental health in Brazil and its importance to the decision-making process. Descriptive paper on HTA and health economics in Brazil. Databases from government and universities as well as some scientific databases to assess the information are presented. Economic analysis to evaluate interventions in mental health care is a relatively recent addition to the field of health economics; in Brazil, it is also considered a topic within Epidemiology research area. There have been an increased number of studies developed in high-income countries. However, there are fewer CE studies in low- and middle-income ones. Psychiatric disorders represent a significant burden in developing countries, where resources devoted to health care are even scarcer.

  10. Driver Gene Mutations in Stools of Colorectal Carcinoma Patients Detected by Targeted Next-Generation Sequencing.

    Science.gov (United States)

    Armengol, Gemma; Sarhadi, Virinder K; Ghanbari, Reza; Doghaei-Moghaddam, Masoud; Ansari, Reza; Sotoudeh, Masoud; Puolakkainen, Pauli; Kokkola, Arto; Malekzadeh, Reza; Knuutila, Sakari

    2016-07-01

    Detection of driver gene mutations in stool DNA represents a promising noninvasive approach for screening colorectal cancer (CRC). Amplicon-based next-generation sequencing (NGS) is a good option to study mutations in many cancer genes simultaneously and from a low amount of DNA. Our aim was to assess the feasibility of identifying mutations in 22 cancer driver genes with Ion Torrent technology in stool DNA from a series of 65 CRC patients. The assay was successful in 80% of stool DNA samples. NGS results showed 83 mutations in cancer driver genes, 29 hotspot and 54 novel mutations. One to five genes were mutated in 75% of cases. TP53, KRAS, FBXW7, and SMAD4 were the top mutated genes, consistent with previous studies. Of samples with mutations, 54% presented concomitant mutations in different genes. Phosphatidylinositol 3-kinase/mitogen-activated protein kinase pathway genes were mutated in 70% of samples, with 58% having alterations in KRAS, NRAS, or BRAF. Because mutations in these genes can compromise the efficacy of epidermal growth factor receptor blockade in CRC patients, identifying mutations that confer resistance to some targeted treatments may be useful to guide therapeutic decisions. In conclusion, the data presented herein show that NGS procedures on stool DNA represent a promising tool to detect genetic mutations that could be used in the future for diagnosis, monitoring, or treating CRC. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  11. BRAF mutations in conjunctival melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahl, Christina; Dahmcke, Christina M.

    2016-01-01

    Purpose: To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection. Methods: Data from 139 patients...... with conjunctival melanoma (1960–2012) were collected. Archived conjunctival melanoma samples and premalignant lesions were analysed for BRAF mutations using droplet digital polymerase chain reaction (PCR). Results were associated with clinicopathological features and compared with BRAF V600E oncoprotein stainings...... with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed...

  12. FGFR3 mutations and the skin: report of a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review of the literature

    DEFF Research Database (Denmark)

    Blomberg, M; Jeppesen, E M; Skovby, F

    2010-01-01

    Fibroblast growth factor receptor 3 (FGFR3) gene mutations in the germline are well-known causes of skeletal syndromes. Somatic FGFR3 mutations have been found in malignant neoplasms and more recently in several cutaneous elements. We present a 14-year-old girl with mild hypochondroplasia who...... developed acanthosis nigricans. The report of a K650Q mutation in the FGFR3 gene in a similar case prompted us to conduct a point mutation analysis. The K650Q mutation was confirmed, but in contrast to the previous case, we additionally report findings of hyperinsulinemia. In the recent literature......, an increasing number of different cutaneous elements have been found to harbor mutations of FGFR3, suggesting that FGFR3 plays a role in the pathogenesis of these elements. We review the present literature, describing studies in which FGFR3 mutations have been investigated in skin lesions: primarily seborrheic...

  13. Heparin pharmacovigilance in Brazil.

    Science.gov (United States)

    Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R de M; Barros, Fabiana C R de; Carvalho, Maria das Graças; Perini, Edson

    2011-01-01

    To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

  14. Region of Southern Brazil

    Directory of Open Access Journals (Sweden)

    Marcelo Moreno

    2012-01-01

    Full Text Available Cutaneous melanoma (CM is responsible for 75% of deaths from malignant skin cancer. The incidence of CM in the southern region of Brazil, particularly in the western region of Santa Catarina, is possibly higher than estimated. In this study, the clinical and epidemiological profile of patients with CM treated in the western region of Santa Catarina was examined. A cross-sectional study was performed with patients diagnosed with CM from January 2002 to December 2009, from 78 counties of the western region of the state of Santa Catarina. Data were collected using a protocol adapted from the Brazilian Melanoma Group and 503 patients were evaluated. The incidence and prevalence of CM found in this region are much higher than those found elsewhere in the country. This fact is most likely due to the phenotypic characteristics of the population and the high incidence of UV radiation in this region due to its location in southern Brazil, as is the case in the countries of Oceania.

  15. CIVIL JUSTICE IN BRAZIL

    Directory of Open Access Journals (Sweden)

    T. A.A. Wambier

    2016-01-01

    Full Text Available This study deals in a succinct way with the Brazilian model of civil procedural law. There is an historical approach specifically about Portuguese law which was in force in Brazil at the beginning (until 1832, after what there comes a brief description of the judiciary structure (courts and judges and only then we talk about the scope of civil procedure, its fundamental principles and, in a “law in practice” approach, access to justice. The role of a judge towards deciding “according to statutes and evidence” is analysed and the current importance of case law is deeply focused, mainly according to the new CPC (in force since 2015 and so are appellate proceedings, class actions, enforcement proceedings and ADR. The last items concern the role and the importance of academia, and some interesting cultural observations, where we deal with the very serious crisis, both ethical and economic, that Brazil is living now, in the political sphere. The judiciary branch is now our only hope.

  16. A DESCRIPTIVE STUDY OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN BRAZIL, 2009 - 2010.

    Science.gov (United States)

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-11-03

    Influenza A viruses undergo frequent antigenic mutations and may thus cause seasonal epidemics and pandemics. The aim of this study was to recover the epidemiological history of the pandemic influenza A(H1N1)pdm09 in Brazil. A descriptive study was conducted in 2009-2010. The Brazilian Information System for reportable diseases (SINAN) was the data source. A total of 105,054 suspected cases of influenza A(H1N1)pdm09 were reported to SINAN. Of these, 53,797 (51.2%) were classified as the new influenza virus subtype. Among the confirmed cases, 56.7% were female, the mean age was 26.31 (SD ± 18.1) years. Fever was the most common sign among the confirmed cases (99.7%) and the presence of comorbidities was reported in 32.5% of cases. In 2009 there were confirmed cases in all 26 Brazilian States and the Federal District. The incidence (per 100,000 inhabitants) of severe influenza in the population was 28.0 in 2009 and 0.5 in 2010. The states of Paraná (301.3), Santa Catarina (36.0) and Rio Grande do Sul (27.4) presented the highest incidence; 46.4% of the confirmed cases were hospitalized and 47,643 were cured (93.8%). The case-fatality rate was 3.9% in 2009. The pandemic virus A(H1N1)pdm09 hit Brazil between April/2009 and December/2010 with an important difference in the geographic pattern distribution of the cases from the northeast to the south of the country. Children and young adults were the most affected. The limitations of the study were data quality and inconsistencies in the final classification of cases in SINAN. This study highlights the urgent need for improvements in the surveillance of emerging diseases in Brazil.

  17. Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi.

    Science.gov (United States)

    Möller, Inga; Murali, Rajmohan; Müller, Hansgeorg; Wiesner, Thomas; Jackett, Louise A; Scholz, Simone L; Cosgarea, Ioana; van de Nes, Johannes Ap; Sucker, Antje; Hillen, Uwe; Schilling, Bastian; Paschen, Annette; Kutzner, Heinz; Rütten, Arno; Böckers, Martin; Scolyer, Richard A; Schadendorf, Dirk; Griewank, Klaus G

    2017-03-01

    Blue nevi are common melanocytic tumors arising in the dermal layer of the skin. Similar to uveal melanomas, blue nevi frequently harbor GNAQ and GNA11 mutations. Recently, recurrent CYSLTR2 and PLCB4 mutations were identified in uveal melanomas not harboring GNAQ or GNA11 mutations. All four genes (GNAQ, GNA11, CYSLTR2, and PLCB4) code for proteins involved in the same signaling pathway, which is activated by mutations in these genes. Given the related functional consequences of these mutations and the known genetic similarities between uveal melanoma and blue nevi, we analyzed a cohort of blue nevi to investigate whether CYSLTR2 and PLCB4 mutations occur in tumors lacking GNAQ or GNA11 mutations (as in uveal melanoma). A targeted next-generation sequencing assay covering known activating mutations in GNAQ, GNA11, CYSLTR2, PLCB4, KIT, NRAS, and BRAF was applied to 103 blue nevi. As previously reported, most blue nevi were found to harbor activating mutations in GNAQ (59%, n=61), followed by less frequent mutations in GNA11 (16%, n=17). Additionally, one BRAF (1%) and three NRAS (3%) mutations were detected. In three tumors (3%) harboring none of the aforementioned gene alterations, CYSLTR2 mutations were identified. All three CYSLTR2 mutations were the same c.386T>A, L129Q mutation previously identified in uveal melanoma that has been shown to lead to increased receptor activation and signaling. In summary, our study identifies CYSLTR2 L129Q alterations as a previously unrecognized activating mutation in blue nevi, occuring in a mutually exclusive fashion with known GNAQ and GNA11 mutations. Similar to GNAQ and GNA11 mutations, CYSLTR2 mutations, when present, are likely defining pathogenetic events in blue nevi.

  18. Reversible optic neuropathy with OPA1 exon 5b mutation

    DEFF Research Database (Denmark)

    Cornille, K.; Milea, D.; Amati-Bonneau, P.

    2008-01-01

    A new c.740G>A (R247H) mutation in OPA1 alternate spliced exon 5b was found in a patient presenting with bilateral optic neuropathy followed by partial, spontaneous visual recovery. R247H fibroblasts from the patient and his unaffected father presented unusual highly tubular mitochondrial network......, significant increased susceptibility to apoptosis, oxidative phosphorylation uncoupling, and altered OPA1 protein profile, supporting the pathogenicity of this mutation. These results suggest that the clinical spectrum of the OPA1-associated optic neuropathies may be larger than previously described......, and that spontaneous recovery may occur in cases harboring an exon 5b mutation Udgivelsesdato: 2008/5...

  19. Hemochromatosis (HFE gene mutations in Brazilian chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    F.V. Perícole

    2005-09-01

    Full Text Available Patients with chronic renal insufficiency (CRI have reduced hemoglobin levels, mostly as a result of decreased kidney production of erythropoietin, but the relation between renal insufficiency and the magnitude of hemoglobin reduction has not been well defined. Hereditary hemochromatosis is an inherited disorder of iron metabolism. The importance of the association of hemochromatosis with treatment for anemia among patients with CRI has not been well described. We analyzed the frequency of the C282Y and H63D mutations in the HFE gene in 201 Brazilian individuals with CRI undergoing hemodialysis. The analysis of the effects of HFE mutations on iron metabolism and anemia with biochemical parameters was possible in 118 patients of this study (hemoglobin, hematocrit, ferritin levels, transferrin saturation, and serum iron. A C282Y heterozygous mutation was found in 7/201 (3.4% and H63D homozygous and heterozygous mutation were found in 2/201 (1.0% and 46/201 (22.9%, respectively. The allelic frequencies of the HFE mutations (0.017 for C282Y mutation and 0.124 for H63D mutation did not differ between patients with CRI and healthy controls. Regarding the biochemical parameters, no differences were observed between HFE heterozygous and mutation-negative patients, although ferritin levels were not higher among patients with the H63D mutation (P = 0.08. From what we observed in our study, C282Y/H63D HFE gene mutations are not related to degrees of anemia or iron stores in CRI patients receiving intravenous iron supplementation (P > 0.10. Nevertheless, the present data suggest that the H63D mutation may have an important function as a modulating factor of iron overload in these patients.

  20. Beta-thalassaemia mutations in northern India (Delhi).

    Science.gov (United States)

    Madan, N; Sharma, S; Rusia, U; Sen, S; Sood, S K

    1998-03-01

    The present study was undertaken to define beta-thalassaemia mutations prevalent in northern India (Delhi). Forty six children of beta-thalassaemia major and their families were investigated. DNA was extracted from leucocytes and screened for mutations prevalent in the Indian population. These mutations included 619bp deletion, IVS 1-1 (G-T), IVS 1-5 (G-C), frameshift mutations FS 8/9 (+G), FS 41/42 (-CTTT), Codon 16(-C), Codon 15 (G-A), codon 30 (G-C), IVS 1-110 (G-A) and -88 (C-T). 619 bp deletion mutation was detected directly by amplification of DNA by PCR followed by agarose gel electrophoresis. Other mutations were studied by DNA amplification and dot blot hybridization using synthetic normal and mutant oligonucleotide probes labelled at 5' end with gamma-32 P-ATP. Five mutations accounted for all the chromosomes in 46 patients. 619 bp deletion mutation was found to be the commonest mutation (34.8%) followed by IVS 1-5 (G-C) in 22.8 per cent, IVS 1-1 (G-T) in 19.6 per cent, FS 8/9 (+G) in 13 per cent and FS 41/42 (-CTTT) in 9.8 per cent. Nineteen (41.3%) patients were homozygous and 27 (58.7%) double heterozygous for different beta-thalassaemia mutations. This observation of limited number of mutations is significant and will be useful in planning strategies for prenatal diagnosis of beta-thalassaemia in northern India.

  1. The transcriptional landscape and mutational profile of lung adenocarcinoma

    National Research Council Canada - National Science Library

    Seo, Jeong-Sun; Ju, Young Seok; Lee, Won-Chul; Shin, Jong-Yeon; Lee, June Koo; Bleazard, Thomas; Lee, Junho; Jung, Yoo Jin; Kim, Jung-Oh; Shin, Jung-Young; Yu, Saet-Byeol; Kim, Jihye; Lee, Eung-Ryoung; Kang, Chang-Hyun; Park, In-Kyu; Rhee, Hwanseok; Lee, Se-Hoon; Kim, Jong-Il; Kang, Jin-Hyoung; Kim, Young Tae

    2012-01-01

    .... Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions...

  2. Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2G in a European patient.

    Science.gov (United States)

    Olivé, Montse; Shatunov, Alexey; Gonzalez, Laura; Carmona, Olga; Moreno, Dolores; Quereda, Lidia Gonzalez; Martinez-Matos, J A; Goldfarb, Lev G; Ferrer, Isidro

    2008-12-01

    A 27-year-old woman of Moldavian origin presented at the age of 15 with progressive proximal limb weakness and painful cramps in her calf muscles. Clinical examination revealed prominent muscle weakness in proximal muscles of the lower extremities and distal anterior compartment of legs, and mild weakness in shoulder girdle muscles. In addition, she had marked calf hypertrophy, muscle atrophy involving the anterior and posterior compartments of the thighs, and the distal anterior compartment of legs, as well as mild scapular winging and hyperlordosis. A muscle biopsy taken from the biceps brachii showed mild dystrophic changes, absent vacuoles, and abundant lobulated fibers. Immunofluorescence and Western blot assays demonstrated complete telethonin deficiency. Molecular analysis revealed a homozygous Trp25X mutation in the telethonin (TCAP) gene resulting in termination of transcription at an early point. Four families from Brazil with telethonin deficiency have previously been reported and classified as LGMD2G, but the actual frequency of this disease is unknown. With this current identification of a case outside the Brazilian population, telethonin mutation-associated LGMD should be considered worldwide.

  3. Ornithine aminotransferase deficiency : diagnostic difficulties in neonatal presentation

    NARCIS (Netherlands)

    Cleary, M A; Dorland, L; de Koning, T J; Poll-The, B T; Duran, M; Mandell, R; Shih, V E; Berger, R; Olpin, S E; Besley, G T N

    2005-01-01

    We describe two unrelated cases of ornithine aminotransferase (OAT) deficiency with rare neonatal presentation of hyperammonaemia. The diagnosis in the neonatal presentation of OAT deficiency is hampered as hyperornithinaemia is absent. Enzyme and mutation studies confirmed the diagnosis. OAT

  4. RBFOX1 and RBFOX3 mutations in rolandic epilepsy

    DEFF Research Database (Denmark)

    Lal, Dennis; Reinthaler, Eva M; Altmüller, Janine

    2013-01-01

    mutation (p.A233Vfs*74) and a hexanucleotide deletion (p.A299_A300del), and a novel nonsense mutation in RBFOX3 (p.Y287*). Although the three variants were inherited from unaffected parents, they were present in all family members exhibiting the RE trait clinically or electroencephalographically with only...... one exception. In contrast, no deleterious mutations of RBFOX1 and RBFOX3 were found in the exomes of 6503 non-RE subjects deposited in the Exome Variant Server database. The observed RBFOX3 exon 3 deletion and nonsense mutation suggest that RBFOX3 represents a novel risk factor for RE, indicating...... that exon deletions and truncating mutations of RBFOX1 and RBFOX3 contribute to the genetic variance of partial and generalized idiopathic epilepsy syndromes....

  5. Experimental Design to Evaluate Directed Adaptive Mutation in Mammalian Cells

    Science.gov (United States)

    Chiaro, Christopher R; May, Tobias

    2014-01-01

    Background We describe the experimental design for a methodological approach to determine whether directed adaptive mutation occurs in mammalian cells. Identification of directed adaptive mutation would have profound practical significance for a wide variety of biomedical problems, including disease development and resistance to treatment. In adaptive mutation, the genetic or epigenetic change is not random; instead, the presence and type of selection influences the frequency and character of the mutation event. Adaptive mutation can contribute to the evolution of microbial pathogenesis, cancer, and drug resistance, and may become a focus of novel therapeutic interventions. Objective Our experimental approach was designed to distinguish between 3 types of mutation: (1) random mutations that are independent of selective pressure, (2) undirected adaptive mutations that arise when selective pressure induces a general increase in the mutation rate, and (3) directed adaptive mutations that arise when selective pressure induces targeted mutations that specifically influence the adaptive response. The purpose of this report is to introduce an experimental design and describe limited pilot experiment data (not to describe a complete set of experiments); hence, it is an early report. Methods An experimental design based on immortalization of mouse embryonic fibroblast cells is presented that links clonal cell growth to reversal of an inactivating polyadenylation site mutation. Thus, cells exhibit growth only in the presence of both the countermutation and an inducing agent (doxycycline). The type and frequency of mutation in the presence or absence of doxycycline will be evaluated. Additional experimental approaches would determine whether the cells exhibit a generalized increase in mutation rate and/or whether the cells show altered expression of error-prone DNA polymerases or of mismatch repair proteins. Results We performed the initial stages of characterizing our system

  6. Experimental design to evaluate directed adaptive mutation in Mammalian cells.

    Science.gov (United States)

    Bordonaro, Michael; Chiaro, Christopher R; May, Tobias

    2014-12-09

    We describe the experimental design for a methodological approach to determine whether directed adaptive mutation occurs in mammalian cells. Identification of directed adaptive mutation would have profound practical significance for a wide variety of biomedical problems, including disease development and resistance to treatment. In adaptive mutation, the genetic or epigenetic change is not random; instead, the presence and type of selection influences the frequency and character of the mutation event. Adaptive mutation can contribute to the evolution of microbial pathogenesis, cancer, and drug resistance, and may become a focus of novel therapeutic interventions. Our experimental approach was designed to distinguish between 3 types of mutation: (1) random mutations that are independent of selective pressure, (2) undirected adaptive mutations that arise when selective pressure induces a general increase in the mutation rate, and (3) directed adaptive mutations that arise when selective pressure induces targeted mutations that specifically influence the adaptive response. The purpose of this report is to introduce an experimental design and describe limited pilot experiment data (not to describe a complete set of experiments); hence, it is an early report. An experimental design based on immortalization of mouse embryonic fibroblast cells is presented that links clonal cell growth to reversal of an inactivating polyadenylation site mutation. Thus, cells exhibit growth only in the presence of both the countermutation and an inducing agent (doxycycline). The type and frequency of mutation in the presence or absence of doxycycline will be evaluated. Additional experimental approaches would determine whether the cells exhibit a generalized increase in mutation rate and/or whether the cells show altered expression of error-prone DNA polymerases or of mismatch repair proteins. We performed the initial stages of characterizing our system and have limited preliminary data

  7. Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening.

    Science.gov (United States)

    Silva, Cassiano Augusto Braga; Barreto, Fellype Carvalho; Dos Reis, Marlene Antonia; Moura Junior, José Andrade; Cruz, Constança Margarida Sampaio

    2016-01-01

    Fabry disease (FD) is a lysosomal storage disorder caused by enzyme α galactosidase A (α-Gal A) deficiency due to mutations in the galactosidase alpha (GLA) gene. It leads to damage several organs, such as the kidneys, due to progressive accumulation of glycosphingolipids. To estimate the prevalence of FD among male hemodialysis (HD) patients in a northern state of Brazil. Screening was performed using a dried blood spot on filter paper to identify patients with low α-Gal A enzyme activity (≤2.2 µmol/l/h). Those with low enzyme activity underwent genetic analysis of the GLA gene. Family screening was conducted in the index cases. 2,583 male HD patients (age: 52 (18-91 years)) were screened. The α-Gal A assay identified 72 males (2.78%) with low enzyme activity. Genotyping identified 3 patients with GLA mutations: W204X, A368T, both previously reported; and C52F, a novel missense mutation. Only the patient with W204X mutation had classic FD. The prevalence rate was 0.12%. Family screening of the index cases identified 23 family members with the same mutations. The prevalence of FD amongst male HD patients found in the Northern of Brazil was low (0.12%). However, family screening of the 3 index cases identified family members at an early stage of the disease, which may benefit from earlier treatment. © 2016 S. Karger AG, Basel.

  8. An ancient founder mutation in PROKR2 impairs human reproduction.

    Science.gov (United States)

    Avbelj Stefanija, Magdalena; Jeanpierre, Marc; Sykiotis, Gerasimos P; Young, Jacques; Quinton, Richard; Abreu, Ana Paula; Plummer, Lacey; Au, Margaret G; Balasubramanian, Ravikumar; Dwyer, Andrew A; Florez, Jose C; Cheetham, Timothy; Pearce, Simon H; Purushothaman, Radhika; Schinzel, Albert; Pugeat, Michel; Jacobson-Dickman, Elka E; Ten, Svetlana; Latronico, Ana Claudia; Gusella, James F; Dode, Catherine; Crowley, William F; Pitteloud, Nelly

    2012-10-01

    Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.

  9. Number of rare germline CNVs and TP53 mutation types.

    Science.gov (United States)

    Silva, Amanda G; Achatz, Isabel Maria W; Krepischi, Ana Cv; Pearson, Peter L; Rosenberg, Carla

    2012-12-21

    The Li-Fraumeni syndrome (LFS), an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors, is caused by different highly penetrant germline mutations in the TP53 gene; each separate mutation has dissimilar functional and phenotypic effects, which partially clarifies the reported heterogeneity between LFS families. Increases in copy number variation (CNV) have been reported in TP53 mutated individuals, and are also postulated to contribute to LFS phenotypic variability. The Brazilian p.R337H TP53 mutation has particular functional and regulatory properties that differ from most other common LFS TP53 mutations, by conferring a strikingly milder phenotype. We compared the CNV profiles of controls, and LFS individuals carrying either p.R337H or DNA binding domain (DBD) TP53 mutations by high resolution array-CGH. Although we did not find any significant difference in the frequency of CNVs between LFS patients and controls, our data indicated an increased proportion of rare CNVs per genome in patients carrying DBD mutations compared to both controls (p=0.0002***) and p.R337H (0.0156*) mutants. The larger accumulation of rare CNVs in DBD mutants may contribute to the reported anticipation and severity of the syndrome; likewise the fact that p.R337H individuals do not present the same magnitude of rare CNV accumulation may also explain the maintenance of this mutation at relatively high frequency in some populations.

  10. Number of rare germline CNVs and TP53 mutation types

    Directory of Open Access Journals (Sweden)

    Silva Amanda G

    2012-12-01

    Full Text Available Abstract Background The Li-Fraumeni syndrome (LFS, an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors, is caused by different highly penetrant germline mutations in the TP53 gene; each separate mutation has dissimilar functional and phenotypic effects, which partially clarifies the reported heterogeneity between LFS families. Increases in copy number variation (CNV have been reported in TP53 mutated individuals, and are also postulated to contribute to LFS phenotypic variability. The Brazilian p.R337H TP53 mutation has particular functional and regulatory properties that differ from most other common LFS TP53 mutations, by conferring a strikingly milder phenotype. Methods We compared the CNV profiles of controls, and LFS individuals carrying either p.R337H or DNA binding domain (DBD TP53 mutations by high resolution array-CGH. Results Although we did not find any significant difference in the frequency of CNVs between LFS patients and controls, our data indicated an increased proportion of rare CNVs per genome in patients carrying DBD mutations compared to both controls (p=0.0002*** and p.R337H (0.0156* mutants. Conclusions The larger accumulation of rare CNVs in DBD mutants may contribute to the reported anticipation and severity of the syndrome; likewise the fact that p.R337H individuals do not present the same magnitude of rare CNV accumulation may also explain the maintenance of this mutation at relatively high frequency in some populations.

  11. Clinical and genetic characterization of manifesting carriers of DMD mutations.

    Science.gov (United States)

    Soltanzadeh, Payam; Friez, Michael J; Dunn, Diane; von Niederhausern, Andrew; Gurvich, Olga L; Swoboda, Kathryn J; Sampson, Jacinda B; Pestronk, Alan; Connolly, Anne M; Florence, Julaine M; Finkel, Richard S; Bönnemann, Carsten G; Medne, Livija; Mendell, Jerry R; Mathews, Katherine D; Wong, Brenda L; Sussman, Michael D; Zonana, Jonathan; Kovak, Karen; Gospe, Sidney M; Gappmaier, Eduard; Taylor, Laura E; Howard, Michael T; Weiss, Robert B; Flanigan, Kevin M

    2010-08-01

    Manifesting carriers of DMD gene mutations may present diagnostic challenges, particularly in the absence of a family history of dystrophinopathy. We review the clinical and genetic features in 15 manifesting carriers identified among 860 subjects within the United Dystrophinopathy Project, a large clinical dystrophinopathy cohort whose members undergo comprehensive DMD mutation analysis. We defined manifesting carriers as females with significant weakness, excluding those with only myalgias/cramps. DNA extracted from peripheral blood was used to study X-chromosome inactivation patterns. Among these manifesting carriers, age at symptom onset ranged from 2 to 47 years. Seven had no family history and eight had male relatives with Duchenne muscular dystrophy (DMD). Clinical severity among the manifesting carriers varied from a DMD-like progression to a very mild Becker muscular dystrophy-like phenotype. Eight had exonic deletions or duplications and six had point mutations. One patient had two mutations (an exonic deletion and a splice site mutation), consistent with a heterozygous compound state. The X-chromosome inactivation pattern was skewed toward non-random in four out of seven informative deletions or duplications but was random in all cases with nonsense mutations. We present the results of DMD mutation analysis in this manifesting carrier cohort, including the first example of a presumably compound heterozygous DMD mutation. Our results demonstrate that improved molecular diagnostic methods facilitate the identification of DMD mutations in manifesting carriers, and confirm the heterogeneity of mutational mechanisms as well as the wide spectrum of phenotypes. 2010 Elsevier B.V. All rights reserved.

  12. Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides.

    Science.gov (United States)

    Chowdhury, Kaushik; Kumar, Suresh; Sharma, Tanu; Sharma, Ankit; Bhagat, Meenakshi; Kamai, Asangla; Ford, Bridget M; Asthana, Shailendra; Mandal, Chandi C

    2018-01-10

    Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing

  13. Brazil-U.S. Relations

    Science.gov (United States)

    2010-03-05

    component to poverty in Brazil. People of African descent in Brazil, also known as Afro - Brazilians, represent roughly 45% of the country’s...Security & Strategic Review, January 2008. 70 Guila Flint, “Jobim alerta para ameaça de atentados e diz que país deve se preparar para problemas durante...in Brazil, also known as Afro -Brazilians, represent 45% of the country’s population, but constitute 64% of the poor and 69% of the extreme poor.106

  14. D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations.

    Science.gov (United States)

    Yui, Shunsuke; Kurosawa, Saiko; Yamaguchi, Hiroki; Kanamori, Heiwa; Ueki, Toshimitsu; Uoshima, Nobuhiko; Mizuno, Ishikazu; Shono, Katsuhiro; Usuki, Kensuke; Chiba, Shigeru; Nakamura, Yukinori; Yanada, Masamitsu; Kanda, Junya; Tajika, Kenji; Gomi, Seiji; Fukunaga, Keiko; Wakita, Satoshi; Ryotokuji, Takeshi; Fukuda, Takahiro; Inokuchi, Koiti

    2017-10-01

    The clinical impact of KIT mutations in core binding factor acute myeloid leukemia (CBF-AML) is still unclear. In the present study, we analyzed the prognostic significance of each KIT mutation (D816, N822K, and other mutations) in Japanese patients with CBF-AML. We retrospectively analyzed 136 cases of CBF-AML that had gone into complete remission (CR). KIT mutations were found in 61 (45%) of the patients with CBF-AML. D816, N822K, D816 and N822K, and other mutations of the KIT gene were detected in 29 cases (21%), 20 cases (15%), 7 cases (5%), and 5 cases (4%), respectively. The rate of relapse-free survival (RFS) and overall survival (OS) in patients with D816 and with both D816 and N822K mutations was significantly lower than in patients with other or with no KIT mutations (RFS: p mutation was associated with a significantly worse prognosis. In a further multivariate analysis of RFS and OS, D816 mutation was found to be an independent risk factor for significantly poorer prognosis. In the present study, we were able to establish that, of all KIT mutations, D816 mutation alone is an unfavorable prognostic factor.

  15. Co-inheritance of novel ATRX gene mutation and globin (α & β) gene mutations in transfusion dependent beta-thalassemia patients.

    Science.gov (United States)

    Al-Nafie, Awatif N; Borgio, J Francis; AbdulAzeez, Sayed; Al-Suliman, Ahmed M; Qaw, Fuad S; Naserullah, Zaki A; Al-Jarrash, Sana; Al-Madan, Mohammed S; Al-Ali, Rudaynah A; AlKhalifah, Mohammed A; Al-Muhanna, Fahad; Steinberg, Martin H; Al-Ali, Amein K

    2015-06-01

    α-Thalassemia X-linked mental retardation syndrome is a rare inherited intellectual disability disorder due to mutations in the ATRX gene. In our previous study of the prevalence of β-thalassemia mutations in the Eastern Province of Saudi Arabia, we confirmed the widespread coinheritance of α-thalassemia mutation. Some of these subjects have a family history of mental retardation, the cause of which is unknown. Therefore, we investigated the presence or absence of mutations in the ATRX gene in these patients. Three exons of the ATRX gene and their flanking regions were directly sequenced. Only four female transfusion dependent β-thalassemia patients were found to be carriers of a novel mutation in the ATRX gene. Two of the ATRX gene mutations, c.623delA and c.848T>C were present in patients homozygous for IVS I-5(G→C) and homozygous for Cd39(C → T) β-thalassemia mutation, respectively. While the other two that were located in the intronic region (flanking regions), were present in patients homozygous for Cd39(C → T) β-thalassemia mutation. The two subjects with the mutations in the coding region had family members with mental retardation, which suggests that the novel frame shift mutation and the missense mutation at coding region of ATRX gene are involved in ATRX syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The inheritance of pathogenic mitochondrial DNA mutations.

    Science.gov (United States)

    Cree, L M; Samuels, D C; Chinnery, P F

    2009-12-01

    Mitochondrial DNA mutations cause disease in >1 in 5000 of the population, and approximately 1 in 200 of the population are asymptomatic carriers of a pathogenic mtDNA mutation. Many patients with these pathogenic mtDNA mutations present with a progressive, disabling neurological syndrome that leads to major disability and premature death. There is currently no effective treatment for mitochondrial disorders, placing great emphasis on preventing the transmission of these diseases. An empiric approach can be used to guide genetic counseling for common mtDNA mutations, but many families transmit rare or unique molecular defects. There is therefore a pressing need to develop techniques to prevent transmission based on a solid understanding of the biological mechanisms. Several recent studies have cast new light on the genetics and cell biology of mtDNA inheritance, but these studies have also raised new controversies. Here we compare and contrast these findings and discuss their relevance for the transmission of human mtDNA diseases.

  17. SMART GRID: Evaluation and Trend in Brazil

    Directory of Open Access Journals (Sweden)

    Ricardo Moreira da Silva

    2014-09-01

    Full Text Available The Smart Grid is considered the most promising conglomerate of technology to be applied for the improvement and optimization of all power production in electrical engineer. Smart Grid's concept is being more and more recognized for its importance for representing a way to meliorate the energetic efficiency of the electric system, reducing consumption, allowing intensive use of energy generation renewable sources. Therefore, the goal of this article is to explore and present Smart Grid's concepts and its global evolution, so as perform an assessment on Smart Grid's tendencies in Brazil. In order to do this, we shown the concepts of Smart Grid, its benefits and impacts in the electric system's value chain, the barriers to its diffusion in Brazil and the paths of investments' incentives for deployment of the new technology. Accordingly, we reach the conclusion that the researches point to a long and challenging trajectory for the development and implantation of Smart Grid's technology in Brazil, which is still in a embryonic phase of pilot projects for the knowledge and technology development implantation.

  18. Hyperinflation in Brazil, Israel, and Nicaragua revisited

    Science.gov (United States)

    Szybisz, Martín A.; Szybisz, Leszek

    2017-01-01

    The aim of the present work is to address the description of hyperinflation regimens in economy. The spirals of hyperinflation developed in Brazil, Israel, and Nicaragua are revisited. This new analysis of data indicates that the episodes occurred in Brazil and Nicaragua can be understood within the frame of the model available in the literature, which is based on a nonlinear feedback (NLF) characterized by an exponent β > 0. In the NLF model the accumulated consumer price index carries a finite time singularity of the type 1 /(tc - t) (1 - β) / β determining a critical time tc at which the economy would crash. It is shown that in the case of Brazil the entire episode cannot be described with a unique set of parameters because the time series was strongly affected by a change of policy. This fact gives support to the ;so called; Lucas critique, who stated that model's parameters usually change once policy changes. On the other hand, such a model is not able to provide any tc in the case of the weaker hyperinflation occurred in Israel. It is shown that in this case the fit of data yields β → 0. This limit leads to the linear feedback formulation which does not predict any tc. An extension for the NLF model is suggested.

  19. The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers.

    Science.gov (United States)

    Rijken, J A; Niemeijer, N D; Jonker, M A; Eijkelenkamp, K; Jansen, J C; van Berkel, A; Timmers, H J L M; Kunst, H P M; Bisschop, P H L T; Kerstens, M N; Dreijerink, K M A; van Dooren, M F; van der Horst-Schrivers, A N A; Hes, F J; Leemans, C R; Corssmit, E P M; Hensen, E F

    2018-01-01

    Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers). One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Two TP53 germline mutations in a classical Li-Fraumeni syndrome family.

    Science.gov (United States)

    van Hest, Liselotte P; Ruijs, Mariëlle W G; Wagner, Anja; van der Meer, Conny A; Verhoef, Senno; van't Veer, Laura J; Meijers-Heijboer, Hanne

    2007-01-01

    Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited cancer predisposition syndrome characterized by a combination of tumors including sarcoma, breast cancer, brain tumors, adrenocortical carcinoma and leukemia. Germline mutations in the tumor suppressor gene TP53 are associated with LFS. We present a family with LFS in which initially a novel germline TP53 intron 5 splice site mutation was found. A second germline TP53 mutation, the exon 7 Asn235Ser (704A-->G) mutation, was detected in this family through pre-symptomatic DNA testing. This latter mutation has been reported repeatedly in the literature as a pathogenic mutation involved in LFS. We provide evidence for pathogenicity of the novel intron 5 splice site mutation, whereas this evidence is lacking for the exon 7 Asn235Ser (704A-->G) mutation. Our findings emphasize the importance of performing additional tests in case of germline sequence variants with uncertain functional effects.

  1. Ministerio da Educacao e Cultura. Trinta Anos de Organizacao e Situacao Atual (Ministry of Education and Culture [Brazil]. Thirty Years Ago and Now). Volumes I and III.

    Science.gov (United States)

    Porto, Norma Carneiro Monteiro

    The economic rather than the educational aspect of Brazil's Ministry of Education and Culture is presented in this historical summary. The study was done as part of Brazil's national program of educational reform. Brazil is currently re-evaluating its school system with the view of adopting a nationally-administered system similar to that in…

  2. The genus Alterosa Blahnik, 2005 (Trichoptera, Philopotamidae, Philopotaminae) in northeastern Brazil, including the description of three new species and an identification key for the genus

    Science.gov (United States)

    Dumas, Leandro Lourenço; Calor, Adolfo Ricardo; Nessimian, Jorge Luiz

    2013-01-01

    Abstract Alterosa Blahnik, 2005 contains 35 described species distributed in southern and southeastern Brazil. Three new species of Alterosa from northeastern Brazil are described and illustrated, Alterosa amadoi sp. n., Alterosa castroalvesi sp. n. and Alterosa caymmii sp. n., the first records of the genus from northeastern Brazil. An identification key for all known species of the genus is also presented. PMID:23950667

  3. The history of cerebrospinal fluid analysis in Brazil.

    Science.gov (United States)

    Livramento, José Antonio; Machado, Luís dos Ramos

    2013-09-01

    Analysis on cerebrospinal fluid (CSF) in neurological diagnosis has always been considered to be a strong point among the main complementary examinations in Brazil. The present paper reviews the main events in the history of CSF in the neurological sciences, with emphasis on the founders of several CSF schools in our country from the beginning of the 20th century to the present time.

  4. Updates on the genus Euphorbia (Euphorbiaceae) in Santa Catarina, Brazil

    DEFF Research Database (Denmark)

    Hassemer, Gustavo; Marques da Silva, Otávio Luis; Funez, Luís Adriano

    2017-01-01

    This contribution presents updates to the knowledge of the species of Euphorbia that occur in Santa Catarina state, southern Brazil. More specifically, we here typify the names E. cyathophora, E. hirtella, E. paranensis and E. stenophylla, and present the first records of E. cyathophora, E...

  5. SDH mutations in cancer.

    Science.gov (United States)

    Bardella, Chiara; Pollard, Patrick J; Tomlinson, Ian

    2011-11-01

    The SDHA, SDHB, SDHC, SDHD genes encode the four subunits of succinate dehydrogenase (SDH; mitochondrial complex II), a mitochondrial enzyme involved in two essential energy-producing metabolic processes of the cell, the Krebs cycle and the electron transport chain. Germline loss-of-function mutations in any of the SDH genes or assembly factor (SDHAF2) cause hereditary paraganglioma/phaeochromocytoma syndrome (HPGL/PCC) through a mechanism which is largely unknown. Owing to the central function of SDH in cellular energy metabolism it is important to understand its role in tumor suppression. Here is reported an overview of genetics, clinical and molecular progress recently performed in understanding the basis of HPGL/PCC tumorigenesis. 2011 Elsevier B.V. All rights reserved.

  6. Designed in Brazil

    Directory of Open Access Journals (Sweden)

    Fernanda Alves da Silva Bonatti

    2010-04-01

    Full Text Available BackgroundHealth design in Brazil has been characterized historically byreplacing imported products with others that are locallymanufactured on a small scale. In January 2007, the HealthDesign Group was created at the National Council forScientific and Technological Development, a partnershipbetween professors and scholars from the University of SaoPaulo. Aiming at documenting some important experiences onthe Brazilian scene to provide historical and methodologicalsubsidies for research, a survey was conducted to find thepioneer experiences that, using the technology available atthe time they were developed, paved the way for the currentresearch.MethodInterviews and surveys in newspapers and journals wereconducted with selection of some Brazilian experiences indesign for health from the end of the 1950s till the early2000s, along with its researchers.ResultsSeveral examples of design for health and historicaldocumentation in Brazil are shown concerning the BrazilianFoundation for the Development of Science Teaching(FUNBEC, the Department of Bioengineering of the HeartInstitute (InCor of the University of Sao Paulo (USP MedicalSchool, the medical equipment at Rede Sarah, the Laboratoryof Design and Materials Selection (LdSM of the FederalUniversity of Rio Grande do Sul (UFRGS in the field ofcraniofacial Orthopedics and some experiences of design areshown in the field of Ophthalmology.ConclusionWe emphasize the cross-disciplinary integration ofsubjects such as medicine, bioengineering and design inall the previously cited experiences. Based on theseexperiences and looking forward to implementing newresearch methods, some members of the Health DesignGroup are involved in the development of solutions forlow vision people: first a high-power-high-optical-qualitymagnifying glass and secondly an innovative readingstand associated with a magnifying glass that has alreadybeen successfully tested in accordance with ethicalstandards by low vision patients

  7. Epidemiologic study on penile cancer in Brazil

    Directory of Open Access Journals (Sweden)

    Luciano A. Favorito

    2008-10-01

    Full Text Available OBJECTIVES: To assess epidemiologic characteristics of penile cancer in Brazil. MATERIALS AND METHODS: From May 2006 to June 2007, a questionnaire was distributed to all Brazilian urologists. Their patients' clinical and epidemiological data was analyzed (age, race, place of residence, history of sexually transmitted diseases, tobacco smoking, performance of circumcision, type of hospital service, as well as the time between the appearance of the symptoms and the diagnosis, the pathological characteristics of the tumor (histological type, degree, localization and size of lesion, stage of disease, the type of treatment performed and the present state of the patient. RESULTS: 283 new cases of penile cancer in Brazil were recorded. The majority of these cases occurred in the north and northeast (53.02% and southeast (45.54% regions. The majority of patients (224, or 78.96% were more than 46 years of age while only 21 patients (7.41% were less than 35 years of age. Of the 283 patients presenting penile cancer, 171 (60.42% had phimosis with the consequent impossibility to expose the glans. A prior medical history positive for HPV infection was reported in 18 of the 283 cases (6.36%. In 101 patients (35.68% tobacco smoking was reported. The vast majority of the cases (n = 207; 73.14% presented with tumors localized in the glans and prepuce. In 48 cases (16.96% the tumor affected the glans, the prepuce and the corpus penis; in 28 cases (9.89% the tumor affected the entire penis. The majority of the patients (n = 123; 75.26% presented with T1 or T2; only 9 patients (3.18% presented with T4 disease. CONCLUSION: Penile cancer is a very frequent pathology in Brazil, predominantly affecting low income, white, uncircumcised patients, living in the north and northeast regions of the country.

  8. Plant mutation breeding and biotechnology

    National Research Council Canada - National Science Library

    Shu, Q. Y; Forster, Brian P; Nakagawa, H

    2012-01-01

    ... (FAO / IAEA) Division of Nuclear Techniques in Food and Agriculture, with its global coordinating and synergistic roles, that plant mutation breeding became a common tool available to plant breeders worldwide. Since these early days the Joint Division continues to play a considerable role in fostering the use of mutation techni...

  9. Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process

    Science.gov (United States)

    Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

    2015-01-01

    The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution. PMID:26177190

  10. Genetic counseling and presymptomatic testing programs for Machado-Joseph Disease: lessons from Brazil and Portugal.

    Science.gov (United States)

    Schuler-Faccini, Lavínia; Osorio, Claudio Maria; Romariz, Flavia; Paneque, Milena; Sequeiros, Jorge; Jardim, Laura Bannach

    2014-03-01

    Machado-Joseph disease (MJD) is an autosomal dominant, late-onset neurological disorder and the most common form of spinocerebellar ataxia (SCA) worldwide. Diagnostic genetic testing is available to detect the disease-causing mutation by direct sizing of the CAG repeat tract in the ataxin 3 gene. Presymptomatic testing (PST) can be used to identify persons at risk of developing the disease. Genetic counseling provides patients with information about the disease, genetic risks, PST, and the decision-making process. In this study, we present the protocol used in PST for MJD and the relevant observations from two centers: Brazil (Porto Alegre) and Portugal (Porto). We provide a case report that illustrates the significant ethical and psychological issues related to PST in late-onset neurological disorders. In both centers, counseling and PST are performed by a multidisciplinary team, and genetic testing is conducted at the same institutions. From 1999 to 2012, 343 individuals sought PST in Porto Alegre; 263 (77%) of these individuals were from families with MJD. In Porto, 1,530 individuals sought PST between 1996 and 2013, but only 66 (4%) individuals were from families with MJD. In Brazil, approximately 50% of the people seeking PST eventually took the test and received their results, whereas 77% took the test in Portugal. In this case report, we highlight several issues that might be raised by the consultand and how the team can extract significant information. Literature about PST testing for MJD and other SCAs is scarce, and we hope this report will encourage similar studies and enable the implementation of PST protocols in other populations, mainly in Latin America.

  11. Genetic counseling and presymptomatic testing programs for Machado-Joseph disease: lessons from Brazil and Portugal

    Directory of Open Access Journals (Sweden)

    Lavínia Schuler-Faccini

    2014-01-01

    Full Text Available Machado-Joseph disease (MJD is an autosomal dominant, late-onset neurological disorder and the most common form of spinocerebellar ataxia (SCA worldwide. Diagnostic genetic testing is available to detect the disease-causing mutation by direct sizing of the CAG repeat tract in the ataxin 3 gene. Presymptomatic testing (PST can be used to identify persons at risk of developing the disease. Genetic counseling provides patients with information about the disease, genetic risks, PST, and the decision-making process. In this study, we present the protocol used in PST for MJD and the relevant observations from two centers: Brazil (Porto Alegre and Portugal (Porto. We provide a case report that illustrates the significant ethical and psychological issues related to PST in late-onset neurological disorders. In both centers, counseling and PST are performed by a multidisciplinary team, and genetic testing is conducted at the same institutions. From 1999 to 2012, 343 individuals sought PST in Porto Alegre; 263 (77% of these individuals were from families with MJD. In Porto, 1,530 individuals sought PST between 1996 and 2013, but only 66 (4% individuals were from families with MJD. In Brazil, approximately 50% of the people seeking PST eventually took the test and received their results, whereas 77% took the test in Portugal. In this case report, we highlight several issues that might be raised by the consultand and how the team can extract significant information. Literature about PST testing for MJD and other SCAs is scarce, and we hope this report will encourage similar studies and enable the implementation of PST protocols in other populations, mainly in Latin America.

  12. MPL mutations in myeloproliferative disorders

    DEFF Research Database (Denmark)

    Beer, Philip A.; Campbell, Peter J.; Scott, Linda M.

    2008-01-01

    Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet c......DNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F......(-) patients and a single V617F(+) patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F(+) ET patients, those with MPL mutations displayed lower hemoglobin...

  13. Emergency medicine in Southern Brazil.

    Science.gov (United States)

    Tannebaum, R D; Arnold, J L; De Negri Filho, A; Spadoni, V S

    2001-02-01

    Emergency medicine is developing rapidly in southern Brazil, where elements of both the Franco-German and the Anglo-American models of emergency care are in place, creating a uniquely Brazilian approach to emergency care. Although emergency medical services (EMS) in Brazil have been directly influenced by the French mobile EMS (SAMU) system, with physicians dispatched by ambulances to the scenes of medical emergencies, the first American-style emergency medicine residency training program in Brazil was recently established at the Hospital de Pronto Socorro (HPS) in Porto Alegre. Emergency trauma care appears to be particularly developed in southern Brazil, where advanced trauma life support is widely taught and SAMU delivers sophisticated trauma care en route to trauma centers designated by the state.

  14. Evolutionary Accessibility of Mutational Pathways

    Science.gov (United States)

    Franke, Jasper; Klözer, Alexander; de Visser, J. Arjan G. M.; Krug, Joachim

    2011-01-01

    Functional effects of different mutations are known to combine to the total effect in highly nontrivial ways. For the trait under evolutionary selection (‘fitness’), measured values over all possible combinations of a set of mutations yield a fitness landscape that determines which mutational states can be reached from a given initial genotype. Understanding the accessibility properties of fitness landscapes is conceptually important in answering questions about the predictability and repeatability of evolutionary adaptation. Here we theoretically investigate accessibility of the globally optimal state on a wide variety of model landscapes, including landscapes with tunable ruggedness as well as neutral ‘holey’ landscapes. We define a mutational pathway to be accessible if it contains the minimal number of mutations required to reach the target genotype, and if fitness increases in each mutational step. Under this definition accessibility is high, in the sense that at least one accessible pathway exists with a substantial probability that approaches unity as the dimensionality of the fitness landscape (set by the number of mutational loci) becomes large. At the same time the number of alternative accessible pathways grows without bounds. We test the model predictions against an empirical 8-locus fitness landscape obtained for the filamentous fungus Aspergillus niger. By analyzing subgraphs of the full landscape containing different subsets of mutations, we are able to probe the mutational distance scale in the empirical data. The predicted effect of high accessibility is supported by the empirical data and is very robust, which we argue reflects the generic topology of sequence spaces. Together with the restrictive assumptions that lie in our definition of accessibility, this implies that the globally optimal configuration should be accessible to genome wide evolution, but the repeatability of evolutionary trajectories is limited owing to the presence of a

  15. Olefin metathesis in Brazil: Brazil is romping it{exclamation_point}; Metatese de olefinas no Brasil: 'Brazil is romping it{exclamation_point}'

    Energy Technology Data Exchange (ETDEWEB)

    Matos, Jose Milton E.; Batista, Nouga C.; Carvalho, Rogerio M.; Santana, Sirlane A. A.; Puzzi, Paula N.; Sanches, Mario; Lima-Neto, Benedito S. [Sao Paulo Univ., Sao Carlos, SP (Brazil). Inst. de Quimica]. E-mail: benedito@iqsc.usp.br

    2007-03-15

    Some aspects of the olefin metathesis reactions are summarized here (types of reactions, mechanism and catalysts). In particular, the research groups that have been working on this chemistry in Brazil are presented. The main goal of this paper is to make this type of reaction more widely known in the Brazilian chemical community. (author)

  16. HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Paula Virginia Michelon Toledo

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality related to human immunodeficiency virus (HIV infection, but in spite of this advance, HIV mutations decrease antiretroviral susceptibility, thus contributing to treatment failure in patients. Genotyping HIV-1 allows the selection of new drugs after initial drug failure. This study evaluated the genotypic profile of HIV-1 isolates from treated (drug-experienced patients in Paraná, Brazil. The prevalence of mutations in reverse transcriptase (RT and protease (PR genes were assessed. We analyzed 467 genotypes of patients with HIV-1 viral loads above 1,000 copies/mL. Mutations at HIV-1 RT and PR genes and previously used ART regimens were recorded. The most prevalent RT mutations were: 184V (68.31%, 215YF (51.6%, 103NS (46%, 41L (39.4%, 67N (38.54%, 210W (23.5%, 190ASE (23.2%, and 181C (17.4%. PR mutations were 90M (33.33%, 82ATFS (29%, 46I (26.8% and 54V (22.2%. The prevalence of mutations was in line with previous national and international reports, except to nonnucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specific drugs, leading to treatment failure in HIV patients.

  17. Algorithms and semantic infrastructure for mutation impact extraction and grounding

    Science.gov (United States)

    2010-01-01

    Background Mutation impact extraction is a hitherto unaccomplished task in state of the art mutation extraction systems. Protein mutations and their impacts on protein properties are hidden in scientific literature, making them poorly accessible for protein engineers and inaccessible for phenotype-prediction systems that currently depend on manually curated genomic variation databases. Results We present the first rule-based approach for the extraction of mutation impacts on protein properties, categorizing their directionality as positive, negative or neutral. Furthermore protein and mutation mentions are grounded to their respective UniProtKB IDs and selected protein properties, namely protein functions to concepts found in the Gene Ontology. The extracted entities are populated to an OWL-DL Mutation Impact ontology facilitating complex querying for mutation impacts using SPARQL. We illustrate retrieval of proteins and mutant sequences for a given direction of impact on specific protein properties. Moreover we provide programmatic access to the data through semantic web services using the SADI (Semantic Automated Discovery and Integration) framework. Conclusion We address the problem of access to legacy mutation data in unstructured form through the creation of novel mutation impact extraction methods which are evaluated on a corpus of full-text articles on haloalkane dehalogenases, tagged by domain experts. Our approaches show state of the art levels of precision and recall for Mutation Grounding and respectable level of precision but lower recall for the task of Mutant-Impact relation extraction. The system is deployed using text mining and semantic web technologies with the goal of publishing to a broad spectrum of consumers. PMID:21143808

  18. Medical and agricultural entomology in Brazil: a historical approach.

    Science.gov (United States)

    Benchimol, J L

    2008-12-01

    Medical Entomology emerged in Brazil in the late nineteenth century, through the initiative of a group of physicians dedicated to researching microorganisms related to diseases of public health importance, especially yellow fever and malaria. They led the institutionalization of Bacteriology and Tropical Medicine in southeast Brazil and the sanitation of coastal cities and, subsequently, rural areas. Medical Entomology provided the professionals who would undertake campaigns against agricultural plagues, as well as the institutionalization of Agronomy and Veterinary Medicine. In the present article, I intend to show how relations between the professionals who gave life to Medical Entomology in Brazil were interwoven and to illustrate their relations with entomologists in other countries. I will also present an overview of the research problems faced by Brazilian entomologists at the turn of the nineteenth century and early decades of the twentieth.

  19. Scorpionism in Brazil in the years 2000 to 2012.

    Science.gov (United States)

    Reckziegel, Guilherme Carneiro; Pinto, Vitor Laerte

    2014-01-01

    Scorpionism is a serious public health problem in Brazil. Nationwide epidemiological analyses of scorpion stings are scarce. In this context, the present study aims to provide an epidemiological analysis of accidents involving scorpions in Brazil. An analytical epidemiological study of the scorpion accidents reported in the Information System for Notifiable Diseases (SINAN) was conducted from 2000 to 2012 in Brazil. During this period, 482,616 accidents and 728 deaths were reported. The annual average incidence and mortality rates per 100,000 inhabitants were 19.6 and 0.030, respectively, with annual average lethality rate of 0.16%. The highest accident frequency was recorded in male subjects, aged 20-49 years, from September to December and in urban areas, except in the northern region of the country, where accidents were most frequent in June and July, and in rural areas. Males up to age 9 and rural areas were defined as an age group and area for greatest death risk, respectively. Scorpionism in Brazil is a predominantly urban health problem that mostly affects people at an economically active age. The Northeast and Southeast hold the majority of cases and deaths, as well as the highest annual incidence and mortality averages, but the Central West and North presented the highest average annual lethality rates. The epidemiological changes described in this study highlight the need for intensifying health surveillance actions to prevent scorpion accidents in Brazil.

  20. Neurofibromatosis presenting with a cherubism phenotype.

    NARCIS (Netherlands)

    Capelle, C.I. van; Hogeman, P.H.; Sijs-Bos, C.J.M. van der; Heggelman, B.G.; Idowu, B.; Slootweg, P.J.; Wittkampf, A.R.M.; Flanagan, A.M.

    2007-01-01

    We report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was

  1. Neurofibromatosis presenting with a cherubism phenotype.

    Science.gov (United States)

    van Capelle, C I; Hogeman, P H G; van der Sijs-Bos, C J M; Heggelman, B G F; Idowu, B; Slootweg, P J; Wittkampf, A R M; Flanagan, A M

    2007-09-01

    We report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was consistent with cherubism. This is the first report in the literature of a child with proven neurofibromatosis type 1 and cherubism without extragnathic lesions. This emphasises that cherubism is a clinical phenotype that can be associated with a number of germline mutations involving SH3BP2, PTPN11 and NF1.

  2. Mutational meltdown in laboratory yeast populations

    NARCIS (Netherlands)

    Zeyl, C.; Mizesko, M.; Visser, de J.A.G.M.

    2001-01-01

    In small or repeatedly bottlenecked populations, mutations are expected to accumulate by genetic drift, causing fitness declines. In mutational meltdown models, such fitness declines further reduce population size, thus accelerating additional mutation accumulation and leading to extinction. Because

  3. Simultaneous mutation detection of three homoeologous genes in wheat by High Resolution Melting analysis and Mutation Surveyor®

    Directory of Open Access Journals (Sweden)

    Vincent Kate

    2009-12-01

    Full Text Available Abstract Background TILLING (Targeting Induced Local Lesions IN Genomes is a powerful tool for reverse genetics, combining traditional chemical mutagenesis with high-throughput PCR-based mutation detection to discover induced mutations that alter protein function. The most popular mutation detection method for TILLING is a mismatch cleavage assay using the endonuclease CelI. For this method, locus-specific PCR is essential. Most wheat genes are present as three similar sequences with high homology in exons and low homology in introns. Locus-specific primers can usually be designed in introns. However, it is sometimes difficult to design locus-specific PCR primers in a conserved region with high homology among the three homoeologous genes, or in a gene lacking introns, or if information on introns is not available. Here we describe a mutation detection method which combines High Resolution Melting (HRM analysis of mixed PCR amplicons containing three homoeologous gene fragments and sequence analysis using Mutation Surveyor® software, aimed at simultaneous detection of mutations in three homoeologous genes. Results We demonstrate that High Resolution Melting (HRM analysis can be used in mutation scans in mixed PCR amplicons containing three homoeologous gene fragments. Combining HRM scanning with sequence analysis using Mutation Surveyor® is sensitive enough to detect a single nucleotide mutation in the heterozygous state in a mixed PCR amplicon containing three homoeoloci. The method was tested and validated in an EMS (ethylmethane sulfonate-treated wheat TILLING population, screening mutations in the carboxyl terminal domain of the Starch Synthase II (SSII gene. Selected identified mutations of interest can be further analysed by cloning to confirm the mutation and determine the genomic origin of the mutation. Conclusion Polyploidy is common in plants. Conserved regions of a gene often represent functional domains and have high sequence

  4. Cornelia de Lange individuals with new and recurrent SMC1A mutations enhance delineation of mutation repertoire and phenotypic spectrum.

    Science.gov (United States)

    Gervasini, Cristina; Russo, Silvia; Cereda, Anna; Parenti, Ilaria; Masciadri, Maura; Azzollini, Jacopo; Melis, Daniela; Aravena, Teresa; Doray, Bérénice; Ferrarini, Alessandra; Garavelli, Livia; Selicorni, Angelo; Larizza, Lidia

    2013-11-01

    We report on the clinical and molecular characterization of eight patients, one male and seven females, with clinical diagnosis of Cornelia de Lange syndrome (CdLS), who were found to carry distinct mutations of the SMC1A gene. Five of the eight mutations are novel, with two involving amino acid residues previously described as altered in a different way. The other three have been reported each in a single case. Comparison of pairs of individuals with the same mutation indicates only partial overlap of their clinical phenotypes. The following novel missense mutations, all affecting highly conserved amino acid residues, were found: p.R398G in the N-terminal coiled-coil domain, p.V651M in the C-terminal coiled-coil/hinge junction, p.R693G in the C-terminal coiled-coil, and p.N1166T and p.L1189F in the C-terminal ABC cassette. The latter is localized in the H-loop, and represents the first mutation involving a functional motif of SMC1A protein. The effect of the mutations on SMC1A protein function has been predicted using four bioinformatic tools. All mutations except p.V651M were scored as pathogenic by three or four of the tools. p.V651M was found in the only male individual of our cohort, who presented with the most severe phenotype. This raises the issue of gender effect when addressing mutation-phenotype correlation for genes such as SMC1A, which incompletely escapes X-inactivation. Our clinical and molecular findings expand the total number of characterized SMC1A-mutated patients (from 44 to 52) and the restricted repertoire of SMC1A mutations (from 29 to 34), contributing to the molecular and clinical signature of SMC1A-based CdLS. © 2013 Wiley Periodicals, Inc.

  5. A novel aspartoacylase (ASPA) gene mutation in Canavan disease.

    Science.gov (United States)

    Durmaz, Asude Alpman; Akin, Haluk; Onay, Huseyin; Vahabi, Ali; Ozkinay, Ferda

    2012-08-01

    Canavan disease is a severe autosomal recessive leukodystrophy characterized by macrocephaly, ataxia, severe motor and mental retardation, dysmyelination, and progressive spongial atrophy of the brain. The human aspartoacylase (ASPA) gene, which catalyzes the deacetylation of N-acetyl-L-aspartate, is mutated in Canavan disease. In the presented family sequencing analysis for the aspartoacylase gene was performed on the blood samples of the parents as the affected child had died due to Canavan disease. After the mutation was detected, prenatal diagnosis was also performed and heterozygous Y88X mutation was detected in the fetus. In this report, we present a novel mutation Y88X within the aspartoacylase gene in a consanguineous family with an affected child diagnosed as Canavan disease.

  6. IRF6 mutation screening in non-syndromic orofacial clefting

    DEFF Research Database (Denmark)

    Leslie, Elizabeth J; Koboldt, Daniel C; Kang, C. J.

    2016-01-01

    Van der Woude syndrome (VWS) is an autosomal dominant malformation syndrome characterized by orofacial clefting (OFC) and lower lip pits. The clinical presentation of VWS is variable and can present as an isolated OFC, making it difficult to distinguish VWS cases from individuals with non......-syndromic OFCs. About 70% of causal VWS mutations occur in IRF6, a gene that is also associated with non-syndromic OFCs. Screening for IRF6 mutations in apparently non-syndromic cases has been performed in several modestly sized cohorts with mixed results. In this study, we screened 1521 trios with presumed non......-syndromic OFCs to determine the frequency of causal IRF6 mutations. We identified seven likely causal IRF6 mutations, although a posteriori review identified two misdiagnosed VWS families based on the presence of lip pits. We found no evidence for association between rare IRF6 polymorphisms and non...

  7. Minisequencing mitochondrial DNA pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Carracedo Ángel

    2008-04-01

    Full Text Available Abstract Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain patients carrying haplogroup J lineages (Fisher's Exact test, P-value Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories.

  8. Access to Environmental Justice in Brazil

    Directory of Open Access Journals (Sweden)

    Mariana Passos Freitas

    2017-07-01

    Full Text Available Abstract: This article aims to show how the equal access to environmental justice occurs in Brazil, even with litigants in inequality, with discrimination on the environmental matter, problems with interpretation of the law and few jurisprudence and information. The increase in the access to justice in Brazil is evident, including the environmental area. As access to justice, we must understand the two basic purposes of the legal system: that the system has to be equally accessible to everybody and that it produces individual and socially fair results, not just the simplistic conceptualization of the number of lawsuits. True access to justice is achieved once the rights of the population are effectively guaranteed. The amount of environmental lawsuits has been increasing each year, mainly after the Brazilian Federal Constitution of 1988, considering that article 225 provided the need for an ecologically balanced environment for present and future generations, besides determining that the government and the community have the duty to preserve it. In addition, the problems are not being adequately resolved at the administrative level. Access to environmental justice should be understood as access to the law, a fair, well-known and effective legal order, with access to the courts, to alternative mechanisms (especially preventive ones and the population materially and psychologically conscious to exercise their rights, by overcoming objective and subjective barriers. For this access, appropriate procedural instruments are necessary to the collective conflicts and the environmental protection, in order to facilitate the protection of the environment in courts, and to overcome barriers to the access to justice in this matter. In Brazil, some procedural instruments have come as a way to guarantee access to environmental justice. They are, mainly: “popular action” and “public civil action”. Both have a specific provision for admission with

  9. EMu: probabilistic inference of mutational processes and their localization in the cancer genome

    Science.gov (United States)

    2013-01-01

    The spectrum of mutations discovered in cancer genomes can be explained by the activity of a few elementary mutational processes. We present a novel probabilistic method, EMu, to infer the mutational signatures of these processes from a collection of sequenced tumors. EMu naturally incorporates the tumor-specific opportunity for different mutation types according to sequence composition. Applying EMu to breast cancer data, we derive detailed maps of the activity of each process, both genome-wide and within specific local regions of the genome. Our work provides new opportunities to study the mutational processes underlying cancer development. EMu is available at http://www.sanger.ac.uk/resources/software/emu/. PMID:23628380

  10. Screening of 99 Danish patients with congenital heart disease for GATA4 mutations

    DEFF Research Database (Denmark)

    Zhang, Litu; Tümer, Zeynep; Jacobsen, Joes Ramsøe

    2006-01-01

    Congenital heart disease (CHD) affects nearly 1% of the population, but only few genes involved in human CHD are presently known. Germ-line mutations in the zinc finger transcription factor GATA4 have been associated with familial cases of atrial and ventricular septal defects and pulmonary...... stenosis. We have screened 99 unrelated Danish patients with different CHD phenotypes to evaluate the prevalence of GATA4 mutations in CHD. No pathogenic mutations were found among the patients, suggesting that GATA4 mutations are relatively rare among CHD patients. Thus, the diagnostic importance of GATA4...... mutations may be confined to familial cases or specific subgroups of CHD phenotypes....

  11. NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

    DEFF Research Database (Denmark)

    Andersen, Morten Tolstrup; Andersen, Mette Klarskov; Christiansen, D.H.

    2008-01-01

    Frameshift mutations of the nucleophosmin gene (NPM1) were recently reported as a frequently occurring abnormality in patients with de novo acute myeloid leukemia (AML). To evaluate the frequency of NPM1 mutations in patients with therapy-related myelodysplasia (t-MDS) and therapy-related AML (t......-/-7, the most frequent abnormalities of t-MDS/t-AML, were not observed (P=0.002). This raises the question whether some of the cases presenting NPM1 mutations were in fact cases of de novo leukemia. The close association to class I mutations and the inverse association to class II mutations suggest...

  12. Filaggrin mutations are genetic modifying factors exacerbating X-linked ichthyosis.

    Science.gov (United States)

    Liao, Haihui; Waters, Alex J; Goudie, David R; Aitken, David A; Graham, Gordon; Smith, Frances J D; Lewis-Jones, Sue; McLean, W H Irwin

    2007-12-01

    Mutations inactivating the STS gene cause X-linked ichthyosis (XLI), whereas null mutations in the FLG gene cause ichthyosis vulgaris. Two brothers presented with XLI. One had a typical fine scaling, and the other was much more severely affected. Both patients carried STS missense mutation T165I. Furthermore, the more severely affected patient also carried heterozygous FLG mutation R501X, which was absent from his mildly affected brother. These data suggest that disrupting epidermal differentiation via different pathways can increase phenotypic severity. Owing to the high population frequency of FLG mutations, filaggrin is a possible genetic modifier in other genodermatoses.

  13. Blau syndrome presenting with ichthyosis.

    Science.gov (United States)

    Masel, Grant; Halbert, Anne

    2005-02-01

    A 12-year-old girl presented with uveitis, joint disease and ichthyosis resembling ichthyosis vulgaris. A biopsy taken from the affected lower leg demonstrated sarcoidal-type granulomas. Synovial biopsy from the knee also showed granulomas. There was a family history of similar clinical features in the patient's younger sister. There were no other systemic features present to suggest a diagnosis of sarcoidosis or other granulomatous disease such as Crohn's disease or tuberculosis. The familial nature of the condition also made these diagnoses less likely. A clinical diagnosis of Blau syndrome was made. Blau syndrome is an uncommon sarcoidosis-like multisystem autosomal-dominant granulomatous disorder caused by mutations in the CARD15 gene. This gene has also recently been found to be a factor in the development of psoriatic arthritis and Crohn's disease. Although many forms of skin involvement have been described in Blau syndrome, this is the first case described of ichthyosis as the primary skin manifestation.

  14. Radiation mutation breeding

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hi Sup; Kim, Jae Sung; Kim, Jin Kyu; Shin, In Chul; Lim, Young Taek

    1998-04-01

    In order to develop an advanced technical knowledge for the selection of better mutants, some of the crops were irradiated and the mutation rate, the survival rate and the method for selction of a mutant were studied. Furthermore, this study aimed to obtain basic data applicable to the development of genetic resources by evaluation and analysis the specific character for selection of the superior mutant and its plant breeding. 1. selection of the mutant with a superior resistance against environment in the principal crops 1) New varieties of mutant rices such as Wonpyeongbyeo, Wongwangbyeo, Winmibyeo, and heogseon chalbeyeo (sticky forma) were registered in the national variety list and made an application to crop variety protection right. They are under review now. 2) We also keep on studying on the number of a grain of 8 lines of excellent mutant rice for the purpose of improvement of breeding . 3) We selected 3 lines which have a resistance to pod and stem blight in large soybean, 31 lines with small grain size and higher yield, 112 lines of soybean of cooking, 7 lines of low lipoxygenase content, and 12 lines with decreased phytic acid content by 20 % compared to the previous level. 2. Selection of advanced Mugunwha (Rose of Sharon) mutant 1) Bagseul, a new variety of mutant, was developed and 30 plantlets of it are being proliferated. 2) Fifty-three lines of a mutant having a various morphologies were selected.

  15. Preoperative RAS Mutational Analysis Is of Great Value in Predicting Follicular Variant of Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Tae Sook Hwang

    2015-01-01

    Full Text Available Follicular variant of papillary thyroid carcinoma (FVPTC, particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6% had a point mutation in one of the BRAF V600E (n=57, BRAF K601E (n=11, or RAS (n=64 genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

  16. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration.

    Science.gov (United States)

    Benajiba, Lina; Le Ber, Isabelle; Camuzat, Agnès; Lacoste, Mathieu; Thomas-Anterion, Catherine; Couratier, Philippe; Legallic, Solenn; Salachas, François; Hannequin, Didier; Decousus, Marielle; Lacomblez, Lucette; Guedj, Eric; Golfier, Véronique; Camu, William; Dubois, Bruno; Campion, Dominique; Meininger, Vincent; Brice, Alexis

    2009-04-01

    TDP-43 (TAR-DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontotemporal lobar degeneration (FTLD) and FTLD associated with MND (FTLD-MND). Mutations in TARDBP gene, coding for TDP-43, were found in patients with pure MND. We now describe TARDBP mutations in two patients with FTLD-MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP-43 may also have a direct pathogenic role in FTLD disorders.

  17. Bladder Cancer and Genetic Mutations.

    Science.gov (United States)

    Zhang, Xiaoying; Zhang, Yangde

    2015-09-01

    The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder

  18. Novel prion protein insert mutation associated with prolonged neurodegenerative illness.

    Science.gov (United States)

    Lewis, V; Collins, S; Hill, A F; Boyd, A; McLean, C A; Smith, M; Masters, C L

    2003-05-27

    Mutations in the prion protein gene (PRNP) are found in approximately 13 to 15% of persons classified as dying from a transmissible spongiform encephalopathy. Point and octapeptide repeat insert and deletion mutations are described in the open reading frame (ORF) of PRNP. The authors present a clinicopathologic study of a patient with a family history of a lengthy and progressive neurodegenerative disorder associated with a novel large octapeptide repeat insert mutation. Neuropathologic examination, including immunohistochemistry for the prion protein, was undertaken. The ORF of PRNP was amplified by PCR, cloned, and sequenced. Homogenate of cerebral tissue underwent Western blot analysis for the prion protein before and after proteinase K treatment. The proband died after a 16-year illness commencing at age 29 years. Confident premortem clinical diagnosis was not achieved despite a brain biopsy. Autopsy examination of the brain confirmed a spongiform encephalopathy. Prion protein immunohistochemistry revealed occasional granular deposits in the cerebellar granular layer. The proband was found to harbor a novel PRNP 168 base pair (bp) insert mutation. The authors have identified a novel 168 bp octapeptide repeat insert mutation. Prion protein immunohistochemistry differs from previous cases harboring seven octapeptide repeat and other long insert mutations. Optimization of PRNP analysis, especially PCR conditions, is essential to avoid overlooking this type of mutation and delay the correct molecular genetic diagnosis.

  19. DRUMS: a human disease related unique gene mutation search engine.

    Science.gov (United States)

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

  20. MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

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    Timur Selçuk Akpınar

    2013-03-01

    Full Text Available OBJECTIVE: The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K were described in patients with essential thrombocythemia (ET and primary (idiopathic myelofibrosis (PMF. The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. METHODS: A total of 77 patients (66 were diagnosed with ET and 11 with PMF and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. RESULTS: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66 and 6 had PMF (54.5%, 6/11. In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively, had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. CONCLUSION: MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation.

  1. Frequent heterogeneous missense mutations of GGAP2 in prostate cancer: implications for tumor biology, clonality and mutation analysis.

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    Yi Cai

    Full Text Available Prostate cancer is the most common visceral malignancy in Western men and a major cause of cancer deaths. Increased activation of the AKT and NFkB pathways have been identified as critical steps in prostate cancer initiation and progression. GGAP2 (GTP-binding and GTPase activating protein 2 is a multidomain protein that contains an N-terminal Ras homology domain (GTPase, followed by a PH domain, a C-terminal GAP domain and an ankyrin repeat domain. GGAP2 can directly activate signaling via both the AKT and NFkB pathways and acts as a node of crosstalk between these pathways. Increased GGAP2 expression is present in three quarters of prostate cancers. Mutations of GGAP2 have been reported in cell lines from other malignancies. We therefore analyzed 84 prostate cancer tissues and 43 benign prostate tissues for somatic mutations in GGAP2 by direct sequencing of individual clones derived from the GAP and GTPase domains of normal and tumor tissue. Overall, half of cancers contained mutant GAP domain clones and in 20% of cancers, 30% or more of clones were mutant in the GAP domain. Surprisingly, the mutations were heterogeneous and nonclonal, with multiple different mutations being present in many tumors. Similar findings were observed in the analysis of the GTPase domain. Mutant GGAP2 proteins had significantly higher transcriptional activity using AP-1 responsive reporter constructs when compared to wild-type protein. Furthermore, the presence of these mutations was associated with aggressive clinical behavior. The presence of high frequency nonclonal mutations of a single gene is novel and represents a new mode of genetic alteration that can promote tumor progression. Analysis of mutations in cancer has been used to predict outcome and guide therapeutic target identification but such analysis has focused on clonal mutations. Our studies indicate that in some cases high frequency nonclonal mutations may need to be assessed as well.

  2. ENU-induced phenovariance in mice: inferences from 587 mutations

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    Arnold Carrie N

    2012-10-01

    Full Text Available Abstract Background We present a compendium of N-ethyl-N-nitrosourea (ENU-induced mouse mutations, identified in our laboratory over a period of 10 years either on the basis of phenotype or whole genome and/or whole exome sequencing, and archived in the Mutagenetix database. Our purpose is threefold: 1 to formally describe many point mutations, including those that were not previously disclosed in peer-reviewed publications; 2 to assess the characteristics of these mutations; and 3 to estimate the likelihood that a missense mutation induced by ENU will create a detectable phenotype. Findings In the context of an ENU mutagenesis program for C57BL/6J mice, a total of 185 phenotypes were tracked to mutations in 129 genes. In addition, 402 incidental mutations were identified and predicted to affect 390 genes. As previously reported, ENU shows strand asymmetry in its induction of mutations, particularly favoring T to A rather than A to T in the sense strand of coding regions and splice junctions. Some amino acid substitutions are far more likely to be damaging than others, and some are far more likely to be observed. Indeed, from among a total of 494 non-synonymous coding mutations, ENU was observed to create only 114 of the 182 possible amino acid substitutions that single base changes can achieve. Based on differences in overt null allele frequencies observed in phenotypic vs. non-phenotypic mutation sets, we infer that ENU-induced missense mutations create detectable phenotype only about 1 in 4.7 times. While the remaining mutations may not be functionally neutral, they are, on average, beneath the limits of detection of the phenotypic assays we applied. Conclusions Collectively, these mutations add to our understanding of the chemical specificity of ENU, the types of amino acid substitutions it creates, and its efficiency in causing phenovariance. Our data support the validity of computational algorithms for the prediction of damage caused by

  3. Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma

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    Bardeesy Nabeel

    2011-02-01

    Full Text Available Abstract Background The genetics of advanced biliary tract cancers (BTC, which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%. KRAS mutations were identified in 3 (13% intra-hepatic cholangiocarcinomas and 1 (33% perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.

  4. Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation.

    Science.gov (United States)

    Figueiredo, B C; Sandrini, R; Zambetti, G P; Pereira, R M; Cheng, C; Liu, W; Lacerda, L; Pianovski, M A; Michalkiewicz, E; Jenkins, J; Rodriguez-Galindo, C; Mastellaro, M J; Vianna, S; Watanabe, F; Sandrini, F; Arram, S B I; Boffetta, P; Ribeiro, R C

    2006-01-01

    An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined. To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation. The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines. 40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%). The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.

  5. Mitochondrial DNA mutations in respiratory complex-I in never-smoker lung cancer patients contribute to lung cancer progression and associated with EGFR gene mutation.

    Science.gov (United States)

    Dasgupta, Santanu; Soudry, Ethan; Mukhopadhyay, Nitai; Shao, Chunbo; Yee, John; Lam, Stephan; Lam, Wan; Zhang, Wei; Gazdar, Adi F; Fisher, Paul B; Sidransky, David

    2012-06-01

    Mitochondrial DNA (mtDNA) mutations were reported in different cancers. However, the nature and role of mtDNA mutation in never-smoker lung cancer patients including patients with epidermal growth factor receptor (EGFR) and KRAS gene mutation are unknown. In the present study, we sequenced entire mitochondrial genome (16.5 kb) in matched normal and tumors obtained from 30 never-smoker and 30 current-smoker lung cancer patients, and determined the mtDNA content. All the patients' samples were sequenced for KRAS (exon 2) and EGFR (exon 19 and 21) gene mutation. The impact of forced overexpression of a respiratory complex-I gene mutation was evaluated in a lung cancer cell line. We observed significantly higher (P = 0.006) mtDNA mutation in the never-smokers compared to the current-smoker lung cancer patients. MtDNA mutation was significantly higher (P = 0.026) in the never-smoker Asian compared to the current-smoker Caucasian patients' population. MtDNA mutation was significantly (P = 0.007) associated with EGFR gene mutation in the never-smoker patients. We also observed a significant increase (P = 0.037) in mtDNA content among the never-smoker lung cancer patients. The majority of the coding mtDNA mutations targeted respiratory complex-I and forced overexpression of one of these mutations resulted in increased in vitro proliferation, invasion, and superoxide production in lung cancer cells. We observed a higher prevalence and new relationship between mtDNA alterations among never-smoker lung cancer patients and EGFR gene mutation. Moreover, a representative mutation produced strong growth effects after forced overexpression in lung cancer cells. Signature mtDNA mutations provide a basis to develop novel biomarkers and therapeutic strategies for never-smoker lung cancer patients. Copyright © 2011 Wiley Periodicals, Inc.

  6. Policing violence in Brazil.

    Science.gov (United States)

    Sena, E

    1999-03-01

    This article is an excerpted summary of a speech on female police and domestic violence. The speech was given by a woman affiliated with the Association of Women Workers at an Oxfam workshop in northern Brazil. This organization successfully lobbied for female police, which resulted in more reports of domestic violence, especially rape. The organization is active in 13 counties. Female police are trained and usually given respect by police chiefs. In one city, in 1997, the appointment of female police resulted in registered reports of 387 cases of violence and hospital reports of 503 cases, of which 14% were child rape. During January-April 1998, there were 126 registered cases and 168 hospital cases. Policewomen formed a partnership over the past 2 years with the Human Rights Group and other popular political groups to train female police about laws. The compulsory course focused on four areas: legal concepts, penalties, and procedures on registration of complaints; the Brazilian Penal Code; civil law; and world judicial bureaucracies. Training includes a 1 month internship with the program's lawyer. Over 20 women have completed the course to date. Training in some cases resulted in greater expertise among the female police than their Police Chiefs. Female police have experienced harassment by local authorities.

  7. [PRRT2 mutation and infantile convulsions].

    Science.gov (United States)

    Mathot, M; Lederer, D; Gerard, S; Gueulette, E; Deprez, M

    2017-10-01

    New genetic techniques have made it possible to better understand the implications of the PRRT2 gene (proline rich transmembrane protein 2) in various neurological disorders. Mutations within this gene are responsible for kinesigenic paroxysmal dyskinesias (PKD) as well as for benign familial infantile epilepsy (BFIE), a disease associating infantile convulsions and choreoathetosis (ICCA), a form of familial hemiplegic migraine (FHM type 4), paroxysmal benign torticollis of childhood, and episodic ataxia. We describe the case of an infant, carrying a mutation of the PRRT2 gene, with a classical presentation. Through her progression over time, we raise the question of systematic use of anti-epileptic drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Inheritance of a new albino mutation in Brazilian free-range black chickens

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    W Jorge

    2008-09-01

    Full Text Available A genetically recessive albino mutation, which inhibits pigment development in the eyes, skin, and feathers of domestic chickens from Brazil, is described. This mutation appeared in a flock of completely black chickens of a private breeder. There are no information on the origin, breed, or specific line of the birds. Pigment inhibition is apparently complete in the feathers and eyes. Bird sight is very impaired, but no histological examination was carried out. Ratios obtained in F2 and backcrossed birds indicate that a single autosomal recessive gene is responsible for the condition. The data suggest that the absence of melanin in the eyes, skin, and feathers (symbol cc is a mutation of the pigmented C wild gene.

  9. Socioeconomic and regional differences in active transportation in Brazil

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    Thiago Hérick de Sá

    2016-01-01

    Full Text Available ABSTRACT OBJECTIVE To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. METHODS By using data from the Health section of 2008’s Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey, we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. RESULTS A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. CONCLUSIONS Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making

  10. Where are the trees outside forest in Brazil?

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    Hubert de Foresta

    2017-09-01

    Full Text Available Trees outside forests (ToF is often a misunderstood category. This is the case in Brazil as shown by the lack of data on ToF reported until now by the country. In this article, ToF are understood in relation to the FAO definition of forest because it is the definition used in Brazil for the National Forest Inventory. I provide a definition of ToF, detail the main sets as inferred from this definition, propose to focus on a category of ToF as an efficient and realistic first step towards the assessment of ToF countrywide, and I illustrate the diversity of ToF-based systems in Brazil, from relatively isolated trees in agroforestry fields to dense mixed tree formations that cannot be distinguished from forests on satellite images. A recent publication has placed Brazil as the world leader in terms of the total biomass carbon stored by one ToF set, trees on agricultural land. This result could stimulate the desire for Brazil to better assess not only trees on agricultural land but also trees on urban land, the two major sets of trees outside forests. The present paper can help those who will undertake this challenging and exciting task.

  11. A review on human attitudes towards reptiles in Brazil.

    Science.gov (United States)

    Alves, Rômulo Romeu Nóbrega; Vieira, Kleber Silva; Santana, Gindomar Gomes; Vieira, Washington Luiz Silva; Almeida, Waltécio Oliveira; Souto, Wedson Medeiros Silva; Montenegro, Paulo Fernando Guedes Pereira; Pezzuti, Juarez Carlos Brito

    2012-11-01

    For many millennia humans and reptiles have interacted, but the attitude of humans towards these animals has depended on culture, environment, and personal experience. At least 719 reptile species are known to occur in Brazil and about 11% of this fauna has been exploited for many different purposes, including bushmeat, leather, ornamental and magic/religious uses, and as folk medicines. Brazil can therefore serve as an interesting case study for better understanding reptile use by human societies, and the present paper catalogues some of the reptile species being used in Brazil and discusses implications for their conservation. A literature review indicated that 81 reptile species are culturally important in this country, with 47 (58%) species having multiple uses, 54 being used for medicinal purposes, 38 as food, 28 for ornamental or decorative purposes, 20 used in magic/religious practices, 18 as pets, and 40 are commonly killed when they come into contact with humans. Regarding their conservation status, 30 (37.5%) are included on State's Red List, Brazilian Red List or the IUCN Red List. There are many forms of interaction between reptiles and humans in Brazil-although most of them are quite negative in terms of wildlife conservation-which reinforces the importance of understanding such uses and interactions in the context of protecting reptiles in Brazil. A better understanding of the cultural, social, and traditional roles of these reptiles is fundamental to establishing management plans for their sustainable use.

  12. Familial hypertrophic cardiomyopathy owing to double heterozygosity for a 403Arg--> Trp mutation in exon 13 of the MYH7 gene and a novel mutation, 453Arg--> His, in exon 14 of the MYH7 gene: A case report.

    Science.gov (United States)

    Haluza, R; Halouzková, S; Buncek, M; Smíd, O; Kvasnicka, J

    2001-01-01

    An unusual clinical history of a 23-year-old male proband with obstructive hypertrophic cardiomyopathy associated with a rare genotype is presented. Genetic analysis of the proband found evidence for two distinct mutations of the MYH7 gene (the gene coding for the beta-myosin heavy chain): 403Arg--> Trp in exon 13 and a novel mutation, 453Arg--> His, in exon 14. A heterozygous site mutation was identified in exon 13 in the proband's father but no mutation site was found in his mother. Thus, the novel mutation in exon 14 is a de novo mutation.

  13. Familial hypertrophic cardiomyopathy owing to double heterozygosity for a 403Arg→ Trp mutation in exon 13 of the MYH7 gene and a novel mutation, 453Arg→ His, in exon 14 of the MYH7 gene: A case report

    Science.gov (United States)

    Haluza, Radovan; Halouzková, Štěpánka; Bunček, Martin; Šmíd, Ondřej; Kvasnička, Jiří

    2001-01-01

    An unusual clinical history of a 23-year-old male proband with obstructive hypertrophic cardiomyopathy associated with a rare genotype is presented. Genetic analysis of the proband found evidence for two distinct mutations of the MYH7 gene (the gene coding for the beta-myosin heavy chain): 403Arg→ Trp in exon 13 and a novel mutation, 453Arg→ His, in exon 14. A heterozygous site mutation was identified in exon 13 in the proband’s father but no mutation site was found in his mother. Thus, the novel mutation in exon 14 is a de novo mutation. PMID:20428263

  14. An unusual presentation of juvenile Alexander disease.

    Science.gov (United States)

    Osorio, Maria Joana; Risen, Sarah; Alper, Gulay

    2012-04-01

    Alexander disease is a rare leukodystrophy that most often presents in infancy but also includes neonatal, juvenile, and adult variants. Juvenile Alexander disease presents primarily with bulbar symptoms between 2 and 12 years of age. The diagnosis is often suggested by the clinical course and brain magnetic resonance image pattern and then confirmed by the presence of a mutation in the glial fibrillary acidic protein gene. A young girl presented with globus sensation and magnetic resonance imaging of the brain revealed abnormalities mainly involving white matter tracts of the medulla oblongata and cerebellum. The presence of a mutation in the glial fibrillary acidic protein gene confirmed the diagnosis of juvenile Alexander disease. A high index of clinical suspicion is necessary for the diagnosis of late-onset presentations of Alexander disease.

  15. Spectrum of α-thalassemia mutations including first observation of - -(FIL) deletion in Hatay Province, Turkey.

    Science.gov (United States)

    Celik, Muhammet Murat; Gunesacar, Ramazan; Oktay, Gonul; Duran, Gulay Gulbol; Kaya, Hasan

    2013-06-01

    Alpha thalassemia (α-thal) is one of the most common genetic disorders in the world. It is characterized by the absence or reduced expression of α-globin genes. The frequency of α-thal mutations in the province of Hatay in South Turkey is unknown. Therefore, in the present study, we aimed to investigate the spectrum of α-thal mutations in this province. Three hundred and nine patients were tested for α-thal mutations by using reverse dot blot hybridization technique and nine different mutations were detected in 97 of them. Among the 9 different mutations found, the most frequent mutations were the -α(3.7) (43.81%), -α2(-5nt) (6.70%), - -(MED) (5.67%) and α2(Poly A2) (2.57%). In the present study, - -(FIL) mutation was detected in a patient for the first time in Turkey. Our results indicated that α-thal mutations are highly heterogeneous and -α(3.7) is the most prevalent mutation in Hatay province of South Turkey. In addition, - -(FIL) mutation was detected in a patient for the first time in Turkey. This new finding may contribute to the establishment of a national mutation database and genetic counseling. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Oil and susta