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Sample records for syndrome disease genes

  1. Genes and Disease: Prader-Willi Syndrome

    Science.gov (United States)

    ... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... 45K) PDF version of this title (3.8M) Gene sequence Genome view see gene locations Entrez Gene ...

  2. Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies.

    Science.gov (United States)

    Urdinguio, Rocio G; Sanchez-Mut, Jose V; Esteller, Manel

    2009-11-01

    Epigenetic mechanisms such as DNA methylation and modifications to histone proteins regulate high-order DNA structure and gene expression. Aberrant epigenetic mechanisms are involved in the development of many diseases, including cancer. The neurological disorder most intensely studied with regard to epigenetic changes is Rett syndrome; patients with Rett syndrome have neurodevelopmental defects associated with mutations in MeCP2, which encodes the methyl CpG binding protein 2, that binds to methylated DNA. Other mental retardation disorders are also linked to the disruption of genes involved in epigenetic mechanisms; such disorders include alpha thalassaemia/mental retardation X-linked syndrome, Rubinstein-Taybi syndrome, and Coffin-Lowry syndrome. Moreover, aberrant DNA methylation and histone modification profiles of discrete DNA sequences, and those at a genome-wide level, have just begun to be described for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, and in other neurological disorders such as multiple sclerosis, epilepsy, and amyotrophic lateral sclerosis. In this Review, we describe epigenetic changes present in neurological diseases and discuss the therapeutic potential of epigenetic drugs, such as histone deacetylase inhibitors.

  3. Tuberous sclerosis complex and polycystic kidney disease contiguous gene syndrome with Moyamoya disease.

    Science.gov (United States)

    Lai, Jonathan; Modi, Lopa; Ramai, Daryl; Tortora, Matthew

    2017-04-01

    Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two diseases sharing close genetic loci on chromosome 16. Due to contiguous gene syndrome, also known as contiguous gene deletion syndrome, the proximity of TSC2 and PKD1 genes increases the risk of co-deletion resulting in a shared clinical presentation. Furthermore, Moyamoya disease (MMD) is a rare vaso-occlusive disease in the circle of Willis. We present the first case of TSC2/PKD1 contiguous gene syndrome in a patient with MMD along with detailed histopathologic, radiologic, and cytogenetic analyses. We also highlight the clinical presentation and surgical complications in this case. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

    Directory of Open Access Journals (Sweden)

    Watkins Casey E

    2011-11-01

    Full Text Available Abstract Chronic Granulomatous Disease (CGD, a disorder of the NADPH oxidase system, results in phagocyte functional defects and subsequent infections with bacterial and fungal pathogens (such as Aspergillus species and Candida albicans. Deletions and missense, frameshift, or nonsense mutations in the gp91phox gene (also termed CYBB, located in the Xp21.1 region of the X chromosome, are associated with the most common form of CGD. When larger X-chromosomal deletions occur, including the XK gene deletion, a so-called "Contiguous Gene Deletion Syndrome" may result. The contiguous gene deletion syndrome is known to associate the Kell phenotype/McLeod syndrome with diseases such as X-linked chronic granulomatous disease, Duchenne muscular dystrophy, and X-linked retinitis pigmentosa. These patients are often complicated and management requires special attention to the various facets of the syndrome.

  5. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

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    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  6. [From gene to disease; EVC, EVC2, and Ellis-van Creveld syndrome].

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    van Hagen, J M; Baart, J A; Gille, J J P

    2005-04-23

    Ellis-van Creveld syndrome is an autosomal recessive disorder characterised by short stature with short limbs, postaxial polydactyly and congenital cardiac defects. The syndrome can be caused by mutations in the EVC gene or the EVC2 gene. The genes are located close to each other in a head-to-head configuration on chromosome 4p16. Clinical diagnosis can be confirmed by DNA analysis, which is currently offered by two laboratories in Italy.

  7. Analysis of Ellis van Creveld syndrome gene products: implications for cardiovascular development and disease.

    Science.gov (United States)

    Sund, Kristen Lipscomb; Roelker, Stephanie; Ramachandran, Vijaya; Durbin, Lisa; Benson, D Woodrow

    2009-05-15

    Mutations identified in a cohort of patients with atrioventricular septal defects as a part of Ellis van Creveld syndrome (EvC syndrome) led us to study the role of two non-homologous genes, EVC and LBN, in heart development and disease pathogenesis. To address the cause of locus heterogeneity resulting in an indistinguishable heart-hand phenotype, we carried out in situ hybridization and immunofluorescence and identified co-localization of Evc and Lbn mRNA and protein. In the heart, expression was identified to be strongest in the secondary heart field, including both the outflow tract and the dorsal mesenchymal protrusion, but was also found in mesenchymal structures of the atrial septum and the atrioventricular cushions. Finally, we studied the transcriptional hierarchy of EVC and LBN but did not find any evidence of direct transcriptional interregulation between the two. Due to the locus heterogeneity of human mutations predicted to result in a loss of protein function, a bidirectional genomic organization and overlapping expression patterns, we speculate that these proteins function coordinately in cardiac development and that loss of this coordinate function results in the characteristics of EvC syndrome.

  8. Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

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    Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

    2015-03-01

    Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

  9. Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

    International Nuclear Information System (INIS)

    Back, Susan J.; Andronikou, Savvas; Kilborn, Tracy; Kaplan, Bernard S.; Darge, Kassa

    2015-01-01

    Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

  10. Cell and gene therapy for genetic diseases: inherited disorders affecting the lung and those mimicking sudden infant death syndrome.

    Science.gov (United States)

    Keeler, Allison M; Flotte, Terence R

    2012-06-01

    Some of the first human gene therapy trials targeted diseases of the lung and provided important information that will continue to help shape future trials. Here we describe both cell and gene therapies for lung diseases such as cystic fibrosis and alpha-1 antitrypsin disorder as well as fatty acid oxidation disorders that mimic sudden infant death syndrome (SIDS). Human clinical gene therapy trials for cystic fibrosis and alpha-1 antitrypsin have been performed using a variety of vectors including adenovirus, adeno-associated virus, and nonviral vectors. No human clinical gene therapy trials have been performed for disorders of fatty acid oxidation; however, important proof-of-principle studies have been completed for multiple fatty acid oxidation disorders. Important achievements have been made and have yet to come for cell and gene therapies for disorders of the lung and those mimicking SIDS.

  11. [From gene to disease; tumor necrosis factor receptor and a syndrome of familial periodic fever

    NARCIS (Netherlands)

    Simon, A.; Drenth, J.P.H.; Meer, J.W.M. van der

    2001-01-01

    Familial Hibernian fever (FHF) is a rare hereditary syndrome that causes periodic attacks of fever and inflammation. It is an autosomal dominantly inherited disorder. The gene involved in FHF encodes for a receptor for tumour necrosis factor (TNFR1). These mutations are thought to result in impaired

  12. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I.

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    Bøe Wolff, A S; Oftedal, B; Johansson, S; Bruland, O; Løvås, K; Meager, A; Pedersen, C; Husebye, E S; Knappskog, P M

    2008-03-01

    Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.

  13. SPECTRAL GRAPH THEORY AND GRAPH ENERGY METRICS SHOW EVIDENCE FOR THE ALZHEIMER'S DISEASE DISCONNECTION SYNDROME INAPOE-4 RISK GENE CARRIERS.

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    Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Hibar, Derrek P; Nir, Talia M; Jack, Clifford R; Weiner, Michael W; Bernstein, Matt A; Thompson, Paul M

    2015-04-01

    Our understanding of network breakdown in Alzheimer's disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. We further assessed supporting metrics - link density and nodal strength - to better interpret our results. Metrics were analyzed in relation to the well-known APOE -4 genetic risk factor for late-onset AD. The number of disconnected cortical regions increased with the number of copies of the APOE -4 risk gene in people with AD. Each additional copy of the APOE -4 risk gene may lead to more dysfunctional networks with weakened or abnormal connections, providing evidence for the previously hypothesized "disconnection syndrome".

  14. Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression

    NARCIS (Netherlands)

    Z. Brkic (Zana); M. de Maria; C.G. van Helden-Meeuwsen; J.P. van de Merwe (Joop); P.L.A. van Daele (Paul); V.A.S.H. Dalm (Virgil); M.E. Wildenberg; W. Beumer (Wouter); H.A. Drexhage (Hemmo); M.A. Versnel (Marjan)

    2013-01-01

    textabstractObjective To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called "IFN type I signature", in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and

  15. Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syndrome and association with disease activity and BAFF gene expression

    NARCIS (Netherlands)

    Brkic, Zana; Maria, Naomi I.; van Helden-Meeuwsen, Cornelia G.; van de Merwe, Joop P.; van Daele, Paul L.; Dalm, Virgil A.; Wildenberg, Manon E.; Beumer, Wouter; Drexhage, Hemmo A.; Versnel, Marjan A.

    2013-01-01

    To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called 'IFN type I signature', in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell

  16. [From gene to disease; genetic causes of hearing loss and visual impairment sometimes accompanied by vestibular problems (Usher syndrome)

    NARCIS (Netherlands)

    Pennings, R.J.E.; Kremer, J.M.J.; Deutman, A.F.; Kimberling, W.J.; Cremers, C.W.R.J.

    2002-01-01

    Usher syndrome is an autosomal recessively inherited disease, characterised by sensorineural hearing loss, tapetoretinal degeneration and in some cases vestibular problems. Based on the clinical heterogeneity, the disease can be classified into three clinical types (I, II and III), which have their

  17. Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

    NARCIS (Netherlands)

    Cryns, K; Sivakumaran, TA; Van den Ouweland, JMW; Pennings, RJE; Cremers, CWRJ; Flothmann, K; Young, TL; Smith, RJH; Lesperance, MM; Van Camp, G

    2003-01-01

    WFS1 is a novel gene and encodes an 890 amino-acid glycoprotein (wolframin), predominantly localized in the endoplasmic reticulum. Mutations in WFS1 underlie autosomal recessive Wolfram syndrome and autosomal dominant low frequency sensorineural hearing impairment (LFSNHI) DFNA6/14. In addition,

  18. Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.

    NARCIS (Netherlands)

    Cryns, K.; Sivakumaran, T.A.; Ouweland, J.M.W. van den; Pennings, R.J.E.; Cremers, C.W.R.J.; Flothmann, K.; Young, T.L.; Smith, R.J.H.; Lesperance, M.M.; Camp, G. van

    2003-01-01

    WFS1 is a novel gene and encodes an 890 amino-acid glycoprotein (wolframin), predominantly localized in the endoplasmic reticulum. Mutations in WFS1 underlie autosomal recessive Wolfram syndrome and autosomal dominant low frequency sensorineural hearing impairment (LFSNHI) DFNA6/14. In addition,

  19. Cannabinoid Receptor 1 Gene Polymorphisms and Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome and in Healthy Controls

    Directory of Open Access Journals (Sweden)

    Justyna Kuliczkowska Plaksej

    2014-01-01

    Full Text Available Context. Polycystic ovary syndrome (PCOS is frequently associated with nonalcoholic fatty liver disease (NAFLD. The endocannabinoid system may play a crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid receptor 1 gene (CNR1 may be responsible for individual susceptibility to obesity and related conditions. Objective. To determine the role of genetic variants of CNR1 in the etiopathology of NAFLD in women with PCOS. Design and Setting. Our department (a tertiary referral center conducted a cross-sectional, case-controlled study. Subjects. 173 women with PCOS (aged 20–35 and 125 healthy, age- and weight-matched controls were studied. Methods. Hepatic steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms of CNR1 (rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674 were genotyped. Results. Frequency of the G allele of rs806381 (P<0.025 and the GG genotype of rs10485170 (P<0.03 was significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674 was higher in PCOS women with NAFLD (not significantly, P=0.059. In multivariate stepwise regression, allele G of rs806381 was associated with PCOS + NAFLD phenotype. Conclusion. Our preliminary results suggest the potential role of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women.

  20. "Mowat-Wilson" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.

    Science.gov (United States)

    Zweier, Christiane; Albrecht, Beate; Mitulla, Beate; Behrens, Rolf; Beese, Maike; Gillessen-Kaesbach, Gabriele; Rott, Hans-Dieter; Rauch, Anita

    2002-03-15

    Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with "syndromic Hirschsprung disease" with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617-623] is specific for ZFHX1B mutations. In order to address these open questions we analyzed the ZFHX1B gene in five patients, three of whom had "syndromic Hirschsprung disease" two with and one without the facial phenotype described by Mowat et al. [1998], and two of whom had the distinct facial gestalt without Hirschsprung disease. Analyses of microsatellite markers and newly identified SNPs, and/or FISH with BACs from the ZFHX1B region excluded large deletions in all five patients. Direct sequencing demonstrated truncating ZFHX1B mutations in all four patients with the characteristic facial phenotype, but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. We demonstrate that there is a specific clinical entity with a recognizable facial gestalt, mental retardation and variable MCAs which we propose be called the "Mowat-Wilson syndrome."

  1. Candidate chromosome 1 disease susceptibility genes for Sjogren’s syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

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    Mongini, Patricia K. A.; Kramer, Jill M.; Ishikawa, Tomo-o; Herschman, Harvey; Esposito, Donna

    2014-01-01

    Sjogren’s syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17 Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region, thereby better delineating candidate Aec2 alleles needed for SS xerostomia. PMID:24685748

  2. Genes and Syndromic Hearing Loss.

    Science.gov (United States)

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  3. The frequency of a disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase in sudden infant death syndrome

    DEFF Research Database (Denmark)

    Banner, Jytte; Gregersen, N; Kølvraa, S

    1993-01-01

    syndrome is still a matter of controversy. The present study investigated 120 well-defined cases of sudden infant death syndrome in order to detect the frequency of the most common disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase (G985) compared with the frequency...... in the general population. A highly specific polymerase chain reaction assay was applied on dried blood spots. No over-representation of homo- or heterozygosity for G985 appears to exist in such a strictly defined population, for which reason it may be more relevant to look at a broader spectrum of clinical...... presentations of inherited metabolic disorders and examine a wider range of sudden death in infancy....

  4. A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease.

    Science.gov (United States)

    Metallinos, D L; Bowling, A T; Rine, J

    1998-06-01

    Lethal White Foal Syndrome is a disease associated with horse breeds that register white coat spotting patterns. Breedings between particular spotted horses, generally described as frame overo, produce some foals that, in contrast to their parents, are all white or nearly all white and die shortly after birth of severe intestinal blockage. These foals have aganglionosis characterized by a lack of submucosal and myenteric ganglia from the distal small intestine to the large intestine, similar to human Hirschsprung Disease. Some sporadic and familial cases of Hirschsprung Disease are due to mutations in the endothelin B receptor gene (EDNRB). In this study, we investigate the role of EDNRB in Lethal White Foal Syndrome. A cDNA for the wild-type horse endothelin-B receptor gene was cloned and sequenced. In three unrelated lethal white foals, the EDNRB gene contained a 2-bp nucleotide change leading to a missense mutation (I118K) in the first transmembrane domain of the receptor, a highly conserved region of this protein among different species. Seven additional unrelated lethal white foal samples were found to be homozygous for this mutation. No other homozygotes were identified in 138 samples analyzed, suggesting that homozygosity was restricted to lethal white foals. All (40/40) horses with the frame overo pattern (a distinct coat color pattern that is a subset of overo horses) that were tested were heterozygous for this allele, defining a heterozygous coat color phenotype for this mutation. Horses with tobiano markings included some carriers, indicating that tobiano is epistatic to frame overo. In addition, horses were identified that were carriers but had no recognized overo coat pattern phenotype, demonstrating the variable penetrance of the mutation. The test for this mutant allele can be utilized in all breeds where heterozygous animals may be unknowingly bred to each other including the Paint Horse, Pinto horse, Quarter Horse, Miniature Horse, and Thoroughbred.

  5. Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

    ... A A A Share Plus on Google Plus Alzheimer's & Dementia alz.org | IHaveAlz Overview What Is Dementia ... chapter Join our online community Down Syndrome and Alzheimer's Disease As they age, those affected by Down ...

  6. Sweet's syndrome complicated by Kikuchi's disease and hemophagocytic syndrome which presented with retinoic acid-inducible gene-I in both the skin epidermal basal layer and the cervical lymph nodes.

    Science.gov (United States)

    Koga, Tomohiro; Takano, Kanako; Horai, Yoshiro; Yamasaki, Satoshi; Nakamura, Hideki; Mizokami, Akinari; Ohshima, Koichi; Kawakami, Atsushi

    2013-01-01

    A 21-year-old man was admitted to our hospital with a fever, erythema, cervical lymphadenopathy and pancytopenia. A diagnosis of Sweet's syndrome (SS) with Kikuchi's disease (KD) and hemophagocytic syndrome (HPS) was made based on the results of a bone marrow aspiration along with the results from biopsy specimens of the brachial skin and a cervical lymph node. The expression of retinoic acid-inducible gene-I (RIG-I) in the skin epidermal basal layer as well as in a cervical lymph node was revealed through immunohistochemistry. He successfully entered remission through treatment with prednisolone. This findings of this case indicate that when SS with KD presents as HPS, it may suggest an association with an RIG-I-related innate immunity.

  7. Rett syndrome: genes, synapses, circuits and therapeutics

    Directory of Open Access Journals (Sweden)

    Abhishek eBanerjee

    2012-05-01

    Full Text Available Development of the nervous system proceeds through a set of complex checkpoints which arise from a combination of sequential gene expression and early neural activity sculpted by the environment. Genetic and environmental insults lead to neurodevelopmental disorders which encompass a large group of diseases that result from anatomical and physiological abnormalities during maturation and development of brain circuits. Rett syndrome (RTT is a postnatal neurological disorder of genetic origin, caused by mutations in the X-linked gene MECP2. It features neuropsychiatric abnormalities like motor dysfunctions and mild to severe cognitive impairment. This review discusses several key questions and attempts to evaluate recently developed animal models, cell-type specific function of MeCP2, defects in neural circuit plasticity and possible therapeutic strategies. Finally, we also discuss how genes, proteins and overlapping signaling pathways affect the molecular etiology of apparently unrelated neuropsychiatric disorders, an understanding of which can offer novel therapeutic strategies.

  8. [Post-Lyme disease syndrome].

    Science.gov (United States)

    Błaut-Jurkowska, Justyna; Jurkowski, Marcin

    2016-02-01

    Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non-specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick-borne diseases needs to increase physicians awareness of these issues. © 2016 MEDPRESS.

  9. Pleiotropic genes for metabolic syndrome and inflammation

    DEFF Research Database (Denmark)

    Kraja, Aldi T; Chasman, Daniel I; North, Kari E

    2014-01-01

    Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors...... metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait...... and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664...

  10. [From gene to disease; mutations in the WFS1-gene as the cause of juvenile type I diabetes mellitus with optic atrophy (Wolfram syndrome)

    NARCIS (Netherlands)

    Pennings, R.J.E.; Dikkeschei, L.D.; Cremers, C.W.R.J.; Ouweland, J.M.W. van den

    2002-01-01

    Wolfram syndrome patients are mainly characterised by juvenile onset diabetes mellitus and optic atrophy. A synonym is the acronym DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy, deafness. Diabetes insipidus and sensorineural high-frequency hearing impairment are important additional

  11. [Wolfram syndrome: clinical features, molecular genetics of WFS1 gene].

    Science.gov (United States)

    Tanabe, Katsuya; Matsunaga, Kimie; Hatanaka, Masayuki; Akiyama, Masaru; Tanizawa, Yukio

    2015-02-01

    Wolfram syndrome(WFS: OMIM 222300) is a rare recessive neuro-endocrine degenerative disorder, known as DIDMOAD(Diabetes Insipidus, early-onset Diabetes Mellitus, Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene(WFS1). The WFS1 protein is an endoplasmic reticulum(ER) embedded protein, which functions in ER calcium homeostasis and unfolded protein responses. Dysregulation of these cellular processes results in the development of ER stress, leading to apoptosis. In addition, abundantly present WFS1 protein in insulin secretory granules plays a role in the intra-granular acidification. However, the phenotypic pleiomorphism and molecular complexity of this disease limit the understanding of WFS. Here we review clinical features, molecular mechanisms and mutations of WFS1 gene that relate to this syndrome.

  12. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS)

    DEFF Research Database (Denmark)

    Bøe Wolff, A S; Oftedal, B; Johansson, S

    2008-01-01

    Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms...

  13. A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.

    Science.gov (United States)

    Yang, G C; Croaker, D; Zhang, A L; Manglick, P; Cartmill, T; Cass, D

    1998-06-01

    Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification-created restriction site (ACRS) technique, revealed a dinucleotide TC-->AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.

  14. Behavioral syndromes in Alzheimer's disease.

    Science.gov (United States)

    Devanand, D P; Brockington, C D; Moody, B J; Brown, R P; Mayeux, R; Endicott, J; Sackeim, H A

    1992-01-01

    The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

  15. Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome.

    Science.gov (United States)

    Prasad, Aparna; Rabionet, Raquel; Espinet, Blanca; Zapata, Luis; Puiggros, Anna; Melero, Carme; Puig, Anna; Sarria-Trujillo, Yaris; Ossowski, Stephan; Garcia-Muret, Maria P; Estrach, Teresa; Servitje, Octavio; Lopez-Lerma, Ingrid; Gallardo, Fernando; Pujol, Ramon M; Estivill, Xavier

    2016-07-01

    Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Coexistence of Celiac Disease and Down Syndrome.

    Science.gov (United States)

    Simila, Seppo; Kokkonen, Jourma

    1990-01-01

    Three Finnish patients with Down syndrome and celiac disease are described. The incidence of celiac disease among patients with Down syndrome was calculated to be 20 times greater than in children without Down syndrome, indicating that it should be kept in mind when patients suffer from recurrent diarrhea and/or delayed puberty. (Author/JDD)

  17. Metabolic Syndrome: Genetic Insights into Disease Pathogenesis

    Science.gov (United States)

    Ziki, Maen D. Abou; Mani, Arya

    2016-01-01

    Purpose of review Metabolic syndrome (MetS) is a cluster of inter-related and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2 diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Recent findings Genome-wide association studies (GWAS) have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Another limitation of this approach is the inherent small effect of the common variants, a major barrier for dissecting their cognate pathways. Modest advances in this venue have been also made by genetic studies of kindreds at the extreme ends of quantitative distributions. These efforts have led to the discovery of a number of disease genes with large effects that underlie the association of diverse traits of this syndrome. Summary Substantial progress has been made over the last decade in identification of genetic risk factors associated with the various traits of MetS. The heterogeneity and multifactorial heritability of MetS, however, has been a challenge towards understanding the factors underlying the association of these traits. Genetic investigations of outlier kindreds or homogenous populations with high prevalence for the disease can potentially improve our knowledge of the disease pathophysiology. PMID:26825138

  18. Antiphospholipid syndrome and kidney disease.

    Science.gov (United States)

    Bienaimé, Frank; Legendre, Christophe; Terzi, Fabiola; Canaud, Guillaume

    2017-01-01

    The antiphospholipid syndrome is a common autoimmune disease caused by pathogenic antiphospholipid antibodies, leading to recurrent thrombosis and/or obstetrical complications. Importantly for nephrologists, antiphospholipid antibodies are associated with various renal manifestations including large renal vessel thrombosis, renal artery stenosis, and a constellation of intrarenal lesions that has been termed antiphospholipid nephropathy. This last condition associates various degrees of acute thrombotic microangiopathy, proliferative and fibrotic lesions of the intrarenal vessels, and ischemic modifications of the renal parenchyma. The course of the disease can range from indolent nephropathy to devastating acute renal failure. The pejorative impact of antiphospholipid antibody-related renal complication is well established in the context of systemic lupus erythematous or after renal transplantation. In contrast, the exact significance of isolated antiphospholipid nephropathy remains uncertain. The evidence to guide management of the renal complications of antiphospholipid syndrome is limited. However, the recent recognition of the heterogeneous molecular mechanisms underlying the progression of intrarenal vascular lesions in antiphospholipid syndrome have opened promising tracks for patient monitoring and targeted therapeutic intervention. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Periodontal disease in individuals with Down Syndrome: genetic focus

    Directory of Open Access Journals (Sweden)

    Lícia Bezerra Cavalcante

    2009-12-01

    Full Text Available Fundamental concepts of etiology, inheritance and clinical characteristics of Down syndrome are used in this review as a basis for submission of studies that focus on periodontal disease in individuals with Down syndrome, since almost 100% of them develop the disease in adult life. It is believed that in association with environmental and cultural factors related to hygiene and disabilities of coordination, the immunological characteristics that are found altered in individuals with Down syndrome, such as deficient neutrophil chemotaxis and reduced number of mature T lymphocytes, may contribute to the greater prevalence and severity of periodontal involvement in patients with Down syndrome. Moreover, the pattern of periodontal destruction observed in individuals with Down syndrome is consistent with aggressive periodontitis, with a predominance of periodontopathogens such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythensis during childhood and adolescence of Down’s syndrome patients. It is possible to note a relationship between the development of molecular techniques and the evolution of knowledge about Down syndrome, for example: identification of the trisomy syndrome by observing only part of chromosome 21 (distal long arm; identification of genes in this trisomic region and the pattern of superexpression (or not of these genes. Moreover, in this review future perspectives are presented with regard to better understanding Down syndrome in the genetic context, which will reflect in more individualized and effective clinical treatments that will provide these patients with a better quality of life.

  20. Post-Treatment Lyme Disease Syndrome

    Science.gov (United States)

    ... is CDC concerned about Lyme disease? Post-Treatment Lyme Disease Syndrome Recommend on Facebook Tweet Share Compartir ... Dangers of long-term or alternative treatments for Lyme disease Studies funded by the National Institutes of ...

  1. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. © 2016 Wiley Periodicals, Inc.

  2. Curing genetic disease with gene therapy.

    Science.gov (United States)

    Williams, David A

    2014-01-01

    Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile.

  3. Identification of the gene for Nance-Horan syndrome (NHS).

    Science.gov (United States)

    Brooks, S P; Ebenezer, N D; Poopalasundaram, S; Lehmann, O J; Moore, A T; Hardcastle, A J

    2004-10-01

    The disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and X linked congenital cataract (CXN) overlap on Xp22. To identify the gene or genes responsible for these diseases. Families with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA. A novel gene NHS, with no known function, was identified as causative for NHS. Protein truncating mutations were detected in all three NHS pedigrees, but no mutation was identified in a CXN family, raising the possibility that NHS and CXN may not be allelic. The NHS gene forms a new gene family with a closely related novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than NHS in human fetal tissues. This study reports the independent identification of the gene causative for Nance-Horan syndrome and extends the number of mutations identified.

  4. A rare hereditary disease: Muckle-Wells syndrome

    Directory of Open Access Journals (Sweden)

    Nitya Ramreddy

    2016-08-01

    Full Text Available Cryopyrin associated periodic syndrome (CAPS is a dominantly-inherited autoinflammatory disease, which is included in the group of periodic fever syndromes. It is caused by a defect in the regulation of inflammatory cytokines, particularly interleukin-1β. CAPS encompasses a spectrum of three phenotypes of increasing severity: familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS and neonatal onset multisystem inflammatory disease. We report the case of a 58-year-old male, who had migratory joint pains, daily urticaria, chills, and episodic conjunctivitis since childhood and hearing loss in his 20s with a family history of similar symptoms. He was diagnosed with MWS after being found to have a R262W gene mutation in NLRP3 gene and successfully treated with canakinumab. After his discovery, other 1st and 2nd degree family members with similar complaints were found to have the same genetic mutation and were also successfully treated with canakinumab.

  5. Sjogren Syndrome-Gene Therapy and its Prospective

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    R Rahpeyma

    2003-02-01

    Full Text Available Sjogren syndrome is one of the autoimmune diseases which is characterized by lymphocytic infiltration to exocrine glands and causes keratoconjunctivitis sicca and xerostomia. Today, a large population, with a majority of women over 40, suffer from this disease and have several complications regarding oral health and reduced life quality such as severe dental caries, painful eyes, olfactory and gustatory deficiency, speech, mastication and swallowing discomforts. Unfortunately, these patients do not respond to the conventional therapies. Nowadays in medical world, which its target is basic therapy and not symptomatic one, several gene therapy approaches, have gained importance in treatment of this apparently incurable diseases. Due to the facts that this disease is the second prevelant autoimmune disease, after rheumatoid arthritis, and the conventional therapies of the disease are all relative and symptomatic, researchers have insisted on the basic and causative therapy through gene transfer more than before. In the Present article, through reviewing 58 references containing recent scientific and investigatory findings it has been tried, to consider the pathogenesis and conventional therapies of this syndrome. Another purpose of this study was to investigate several and potentially very effective gene transfer systems and different theraputic genes (mainly membrane water channels, ione transporter molecules, transcription factors, antifungal proteins and free radical scavengers.

  6. Raynaud's Syndrome: a neglected disease.

    Science.gov (United States)

    Poredos, Pavel; Poredos, Peter

    2016-04-01

    Raynaud's Syndrome is a frequent manifestation of digital ischemia which occurs or is aggravated upon exposure to cold temperatures or emotional distress. Primary Raynaud is a benign disease which predominantly affects younger women and is transient without serious sequelae. In contrast, secondary Raynaud is usually one of the manifestations of systemic disease and is, in addition to symptoms of the basic disease, associated with ischemic lesions. The diagnosis of primary Raynaud is mostly based on the clinical presentation. In secondary Raynaud, additional investigating techniques including imaging investigations and laboratory tests for the detection of underline disease are needed. Treatment is based on lifestyle modification, which includes smoking cessation, avoiding low outside temperatures, avoiding the use of vibrating tools and limiting repeated hand actions. Drug treatment consists of calcium-channel blockers, nitroglycerine ointments, prostacyclins and various new drugs such as endothelin receptor antagonists, phosphodiesterase inhibitors and serotonin receptor antagonists. Most of these drugs are effective in less than 50% of treated patients and do not completely abolish vasospastic attacks, but reduce the severity and frequency of attacks. The prostacyclin derivate iloprost is the most promising drug in the management of secondary Raynaud's disease. Other therapeutic procedures including chemical or surgical sympathectomy are obsolete and without any long-term positive effects.

  7. A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

    Directory of Open Access Journals (Sweden)

    Emond Mary

    2007-09-01

    Full Text Available Abstract Background Marfan syndrome (MFS is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. Results We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. Conclusion Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value -6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status. An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.

  8. Gene Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Rachel Denyer

    2012-01-01

    Full Text Available Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

  9. Autoimmune diseases in women with Turner's syndrome

    DEFF Research Database (Denmark)

    Jørgensen, Kristian T; Rostgaard, Klaus; Bache, Iben

    2010-01-01

    OBJECTIVE: In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women with T...

  10. Genetics Home Reference: Huntington disease-like syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Huntington disease-like syndrome Huntington disease-like syndrome Printable PDF Open All Close ... collapse boxes. Description As its name suggests, a Huntington disease -like (HDL) syndrome is a condition that ...

  11. Periodontal disease in primary Sjögren's Syndrome

    DEFF Research Database (Denmark)

    Schjødt, Morten; Christensen, Lisa Bøge; Petersen, P.E.

    2001-01-01

    Sjögren's syndrome, gingivitis, periodontitis, periodontal disease, xerostomia, oral manifestations......Sjögren's syndrome, gingivitis, periodontitis, periodontal disease, xerostomia, oral manifestations...

  12. Moyamoya disease associated with antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Mahmut Abuhandan

    2011-12-01

    Full Text Available Moyamoya (MMD is a disease that often involves the vascular structures of anterior cerebral circulation, particularly the proximal segments of anterior and middle cerebral arteries. The etiology of the disease is unknown. MMD often presents with cerebral ischemia and rarely with cerebral hemorrhage. The pathology is termed Moyamoya syndrome (MMS when the pathological cerebral angiography findings are accompanied by meningitis, neurofibromatosis, neoplasm, Down syndrome or polycystic kidney disease. Autoimmune diseases including Graves’ disease, Behcet’s disease and antiphospholipid syndrome might also lead to the development of MMS. In this manuscript, we presented an interesting case of MMD associated with antiphospholipid syndrome, which is quite a rare cause of acute cerebral infarction in childhood

  13. Mitochondria in complex psychiatric disorders: Lessons from mouse models of 22q11.2 deletion syndrome: Hemizygous deletion of several mitochondrial genes in the 22q11.2 genomic region can lead to symptoms associated with neuropsychiatric disease.

    Science.gov (United States)

    Devaraju, Prakash; Zakharenko, Stanislav S

    2017-02-01

    Mitochondrial ATP synthesis, calcium buffering, and trafficking affect neuronal function and survival. Several genes implicated in mitochondrial functions map within the genomic region associated with 22q11.2 deletion syndrome (22q11DS), which is a key genetic cause of neuropsychiatric diseases. Although neuropsychiatric diseases impose a serious health and economic burden, their etiology and pathogenesis remain largely unknown because of the dearth of valid animal models and the challenges in investigating the pathophysiology in neuronal circuits. Mouse models of 22q11DS are becoming valid tools for studying human psychiatric diseases, because they have hemizygous deletions of the genes that are deleted in patients and exhibit neuronal and behavioral abnormalities consistent with neuropsychiatric disease. The deletion of some 22q11DS genes implicated in mitochondrial function leads to abnormal neuronal and synaptic function. Herein, we summarize recent findings on mitochondrial dysfunction in 22q11DS and extend those findings to the larger context of schizophrenia and other neuropsychiatric diseases. © 2017 WILEY Periodicals, Inc.

  14. Genetic Alterations within the DENND1A Gene in Patients with Polycystic Ovary Syndrome (PCOS)

    DEFF Research Database (Denmark)

    Eriksen, Mette B; Nielsen, Michael F B; Brusgaard, Klaus

    2013-01-01

    Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene...

  15. Recognition of a Kawasaki Disease Shock Syndrome

    Science.gov (United States)

    Kanegaye, John T.; Wilder, Matthew S.; Molkara, Delaram; Frazer, Jeffrey R.; Pancheri, Joan; Tremoulet, Adriana H.; Watson, Virginia E.; Best, Brookie M.; Burns, Jane C.

    2010-01-01

    objective We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. methods We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of ≥20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. results Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances. conclusions Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery

  16. A gene signature for post-infectious chronic fatigue syndrome

    Science.gov (United States)

    Gow, John W; Hagan, Suzanne; Herzyk, Pawel; Cannon, Celia; Behan, Peter O; Chaudhuri, Abhijit

    2009-01-01

    Background At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment. PMID:19555476

  17. A gene signature for post-infectious chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Cannon Celia

    2009-06-01

    Full Text Available Abstract Background At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8 and male healthy control subjects (n = 7. Results Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment.

  18. ASIA syndrome: breast implant and Still's disease

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    Cristhian Armenteros

    2017-10-01

    Full Text Available Connective tissue diseases associated with silicone breast implants have been widely discussed. In the last decade, siliconosis has been included in the autoimmune/inflammatory syndrome induced by adjuvants (ASIA next to Gulf War syndrome, macrophage myofascitis and postvaccination phenomena. The ASIA syndrome may appear as lupus, rheumatoid arthritis, or more rarely, as adult Still's disease. We discuss the case of a patient with prolonged fever and clinical criteria for ASIA and Still's disease. The prostheses were resected and pathology showed absence of breast implant associated anaplastic lymphoma ALK (-. Physicians should be alert to these new entities linked to silicone breast implants

  19. Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome.

    Science.gov (United States)

    Massingham, Lauren J; Johnson, Kirby L; Scholl, Thomas M; Slonim, Donna K; Wick, Heather C; Bianchi, Diana W

    2014-09-01

    Turner syndrome is a sex chromosome aneuploidy with characteristic malformations. Amniotic fluid, a complex biological material, could contribute to the understanding of Turner syndrome pathogenesis. In this pilot study, global gene expression analysis of cell-free RNA in amniotic fluid supernatant was utilized to identify specific genes/organ systems that may play a role in Turner syndrome pathophysiology. Cell-free RNA from amniotic fluid of five mid-trimester Turner syndrome fetuses and five euploid female fetuses matched for gestational age was extracted, amplified, and hybridized onto Affymetrix(®) U133 Plus 2.0 arrays. Significantly differentially regulated genes were identified using paired t tests. Biological interpretation was performed using Ingenuity Pathway Analysis and BioGPS gene expression atlas. There were 470 statistically significantly differentially expressed genes identified. They were widely distributed across the genome. XIST was significantly down-regulated (p Turner syndrome transcriptome from other aneuploidies we previously studied. Manual curation of the differentially expressed gene list identified genes of possible pathologic significance, including NFATC3, IGFBP5, and LDLR. Transcriptomic differences in the amniotic fluid of Turner syndrome fetuses are due to genome-wide dysregulation. The hematologic/immune system differences may play a role in early-onset autoimmune dysfunction. Other genes identified with possible pathologic significance are associated with cardiac and skeletal systems, which are known to be affected in females with Turner syndrome. The discovery-driven approach described here may be useful in elucidating novel mechanisms of disease in Turner syndrome.

  20. Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery.

    Science.gov (United States)

    Verstraeten, Aline; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart

    2016-06-01

    Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-β pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-β antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years. © 2016 WILEY PERIODICALS, INC.

  1. A patient with Werner syndrome and adiponectin gene mutation.

    Science.gov (United States)

    Hashimoto, Naotake; Hatanaka, Sachiko; Yokote, Koutaro; Kurosawa, Hiroko; Yoshida, Tomohiko; Iwai, Rie; Takahashi, Hidenori; Yoshida, Katsuya; Horie, Atsuya; Sakurai, Kenichi; Yagui, Kazuo; Saito, Yasushi; Yoshida, Shouji

    2007-01-01

    Werner syndrome is a premature aging disease characterized by genomic instability and increased cancer risk. Here, we report a 45-year-old diabetic man as the first Werner syndrome patient found to have an adiponectin gene mutation. Showing graying and loss of hair, skin atrophy, and juvenile cataract, he was diagnosed with Werner syndrome type 4 by molecular analysis. His serum adiponectin concentration was low. In the globular domain of the adiponectin gene, I164T in exon 3 was detected. When we examined effects of pioglitazone (15 mg/day) on serum adiponectin multimer and monomer concentrations using selective assays, the patient's relative percentage increased in adiponectin concentration was almost same as that in the 18 diabetic patients without an adiponectin mutation, but the absolute adiponectin concentration was half of those seen in diabetic patients treated with the same pioglitazone dose who had no adiponectin mutation. The response suggested that pioglitazone treatment might help to prevent future Werner syndrome-related acceleration of atherosclerosis. Present and further clinical relevant to atherosclerosis in this patient should be imformative concerning the pathogenesis and treatment of atherosclerosis in the presence of hypoadiponectinemia and insulin resistance.

  2. Associations of platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphisms with circulating PAF-AH levels and risk of coronary heart disease or blood stasis syndrome in the Chinese Han population.

    Science.gov (United States)

    Zheng, Guo-Hua; Xiong, Shang-Quan; Chen, Hai-Ying; Mei, Li-Juan; Wang, Ting

    2014-11-01

    The circulating level of platelet-activating factor acetylhydrolase (PAF-AH) is a novel biomarker to predict the presence of coronary heart disease. PAF-AH gene polymorphisms may be responsible for the variance of circulating PAF-AH levels in individuals. However, the association of PAF-AH gene polymorphisms with circulating PAF-AH levels and the susceptibility to coronary heart disease (CHD) remains unsolved. Blood stasis syndrome (BSS) of CHD is the most common type of TCM syndromes, and a previous study discovered its relationship with the elevated circulating PAF-AH levels. However, the association of gene polymorphisms and CHD with BSS is unclear at present. In this study, four polymorphisms (R92H, I198T, A379V, V279F) of the PAF-AH gene were genotyped in 570 CHD patients, of which 299 had BSS. In addition, 317 unaffected individuals from the same hospitals served as controls. Plasma PAF-AH levels were measured in 155 controls and 271 CHD patients selected randomly, including 139 CHD patients with BSS. In the Chinese Han population, plasma PAF-AH levels in CHD patients with BSS or without BSS were significantly higher (12.9 ± 6.5 and 11.1 ± 5.0 μM, respectively) than in controls (9.3 ± 5.2 μM); this difference still remained significant after adjustment for traditional risk factors or the inflammatory factors. The R92H polymorphism was highly related to the plasma PAF-AH levels and the risk of CHD, especially among patients with BSS, even with the adjustment for the effects of traditional factors. The I198T polymorphism was highly associated with risk of CHD with BSS, but was associated with neither the risk of CHD with no BSS nor with elevated plasma PAF-AH levels.

  3. Genomic imbalances in syndromic congenital heart disease.

    Science.gov (United States)

    Molck, Miriam Coelho; Simioni, Milena; Paiva Vieira, Társis; Sgardioli, Ilária Cristina; Paoli Monteiro, Fabíola; Souza, Josiane; Fett-Conte, Agnes Cristina; Félix, Têmis Maria; Lopes Monlléo, Isabella; Gil-da-Silva-Lopes, Vera Lúcia

    To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  4. Genomic imbalances in syndromic congenital heart disease,

    Directory of Open Access Journals (Sweden)

    Miriam Coelho Molck

    Full Text Available Abstract Objective: To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS. Methods: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH and/or multiplex ligation probe amplification (MLPA were tested by chromosomal microarray analysis (CMA. Results: Clinically significant copy number variations (CNVs ≥300 kb were identified in 10% (8/78 of cases. In addition, potentially relevant CNVs were detected in two cases (993 kb duplication in 15q21.1 and 706 kb duplication in 2p22.3. Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. Conclusion: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.

  5. Inflammatory Lung Disease in Rett Syndrome

    Science.gov (United States)

    De Felice, Claudio; Rossi, Marcello; Chisci, Glauco; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Iacona, Ingrid; Cortelazzo, Alessio; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease. PMID:24757286

  6. Multiple autoimmune syndrome with celiac disease.

    Science.gov (United States)

    Harpreet, Singh; Deepak, Jain; Kiran, B

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  7. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    Science.gov (United States)

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  8. Skip segment Hirschsprung disease and Waardenburg syndrome

    Directory of Open Access Journals (Sweden)

    Erica R. Gross

    2015-04-01

    Full Text Available Skip segment Hirschsprung disease describes a segment of ganglionated bowel between two segments of aganglionated bowel. It is a rare phenomenon that is difficult to diagnose. We describe a recent case of skip segment Hirschsprung disease in a neonate with a family history of Waardenburg syndrome and the genetic profile that was identified.

  9. Triple A syndrome: two novel mutations in the AAAS gene.

    Science.gov (United States)

    Thümmler, Susanne; Huebner, Angela; Baechler-Sadoul, Elisabeth

    2009-01-01

    Triple A syndrome is a rare disease of autosomal recessive inheritance. It was first described in 1978. The typical triad includes adrenocorticotrophic-hormone-resistant glucocorticoid insufficiency, reduced or absent tearing (alacrima) and achalasia. But clinical symptoms can be extremely heterogeneous and of variable clinically expression. This report describes a 7-year-old boy with a 1 year history of fatigue and muscle weakness. Physical examination showed skin and mucosal hyperpigmentation, and hormonal analysis revealed isolated glucocorticoid function. Medical history was marked by megaoesophagus and achalasia. The absence of tears when crying had been noted since birth. In the presence of the classical triad, triple A syndrome was diagnosed. Clinical diagnosis was confirmed by molecular analysis of the AAAS gene on chromosome 12q13. The novel compound heterozygous mutation c.1304delA and c.1292-1294delTTCinsA was found.

  10. Early disease progression of Hurler syndrome

    OpenAIRE

    Kiely, Bridget T.; Kohler, Jennifer L.; Coletti, Hannah Y.; Poe, Michele D.; Escolar, Maria L.

    2017-01-01

    Background Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler?Scheie and Scheie syndromes). Given that the optimal treatment differs be...

  11. [Isaacs's syndrome and associated diseases].

    Science.gov (United States)

    Watanabe, Osamu

    2013-01-01

    Isaacs' syndrome is an antibody-mediated potassium channel disorder. Clinical symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation following muscle contraction, and hyperhidrosis. Hyperexcitability of the peripheral nerve cause these symptoms, which are relieved by administration of Na channel blockers and immunotherapy.The target channel proteins are voltage-gated potassium channels (VGKCs). The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Electrophysiological findings show that antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiological, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve."VGKC antibodies" are also detected in Morvan syndrome (severe insomnia with neuromyotonia and various autonomic disorders) and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC antibodies" are mainly directed toward associated proteins (for example LGI-1, CASPR-2) that complex with VGKCs themselves. The "VGKC antibodies" are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. CASPR-2 antibodies are present in the majority of patients with Morvan syndrome.

  12. Pathological assessment of mismatch repair gene variants in Lynch syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

    2012-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...

  13. Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome

    Directory of Open Access Journals (Sweden)

    Richard Danger

    2018-01-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS, the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group, and 26 samples at or after BOS diagnosis (diagnosis group. An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group. We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1, T-cell leukemia/lymphoma protein 1A (TCL1A, and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p < 0.01 and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

  14. GORHAM-STOUT SYNDROME: PHANTOM BONE DISEASE.

    Science.gov (United States)

    El-Kouba, Gabriel; de Araújo Santos, Romilton; Pilluski, Paulo César; Severo, Antonio; Lech, Osvandré

    2010-01-01

    Gorham-Stout syndrome is a disease that presents idiopathic osteolysis of a bone or closely contiguous area. The etiology is unknown. It is a rare condition that is difficult to diagnose, and its treatment is controversial. It affects individuals irrespective of age or sex. In this study, we conducted a bibliographic review of the disease, specifically focusing on the differential diagnosis, and we demonstrated the follow-up on a patient with this syndrome from the time of its diagnosis, through treatment, to its current state of evolution.

  15. [Gene mutation and clinical phenotype analysis of patients with Noonan syndrome and hypertrophic cardiomyopathy].

    Science.gov (United States)

    Liu, X H; Ding, W W; Han, L; Liu, X R; Xiao, Y Y; Yang, J; Mo, Y

    2017-10-02

    Objective: To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database. Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion: Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

  16. Early disease progression of Hurler syndrome.

    Science.gov (United States)

    Kiely, Bridget T; Kohler, Jennifer L; Coletti, Hannah Y; Poe, Michele D; Escolar, Maria L

    2017-02-14

    Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler-Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening. Information about the natural history of Hurler syndrome may aid in the management of affected infants, contribute to treatment decisions, and facilitate evaluation of treatment effectiveness and prognosis. Thus, the aim of this study was to characterize the progression and timing of symptom onset in infants with Hurler syndrome. Clinical data from 55 patients evaluated at a single center were retrospectively reviewed. Information about each child's medical history was obtained following a standardized protocol including a thorough parent interview and the review of previous medical records. All patients underwent systematic physical and neurodevelopmental evaluations by a multidisciplinary team. Nearly all patients (98%) showed signs of disease during the first 6 months of life. Common early disease manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Other symptoms such as kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference typically appeared slightly later (median age, 8-10 months). During the first 12 months, gross motor development was the most severely affected area of functioning, and a significant number of patients also experienced language delays. Cognition was typically preserved

  17. Metabolic Syndrome: Systems Thinking in Heart Disease.

    Science.gov (United States)

    Dommermuth, Ron; Ewing, Kristine

    2018-03-01

    Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors. MetS is associated with approximately 4-fold increase in the likelihood of developing type 2 diabetes mellitus (T2DM) and a 2-fold increase in the incidence of cardiovascular disease complications. MetS is a progressive, proinflammatory, prothrombotic condition that manifests itself along a broad spectrum of disease. It is associated with hypertension, obstructive sleep apnea, fatty liver disease, gout, and polycystic ovarian syndrome. Intervening in and reversing the pathologic process become more difficult as the disease progresses, highlighting the needs for increased individual and community surveillance and primary prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A novel small deletion in the NHS gene associated with Nance-Horan syndrome.

    Science.gov (United States)

    Li, Huajin; Yang, Lizhu; Sun, Zixi; Yuan, Zhisheng; Wu, Shijing; Sui, Ruifang

    2018-02-05

    Nance-Horan syndrome is a rare X-linked recessive inherited disease with clinical features including severe bilateral congenital cataracts, characteristic facial and dental abnormalities. Data from Chinese Nance-Horan syndrome patients are limited. We assessed the clinical manifestations of a Chinese Nance-Horan syndrome pedigree and identified the genetic defect. Genetic analysis showed that 3 affected males carried a novel small deletion in NHS gene, c.263_266delCGTC (p.Ala89TrpfsTer106), and 2 female carriers were heterozygous for the same variant. All 3 affected males presented with typical Nance-Horan syndrome features. One female carrier displayed lens opacities centered on the posterior Y-suture in both eyes, as well as mild dental abnormalities. We recorded the clinical features of a Chinese Nance-Horan syndrome family and broadened the spectrum of mutations in the NHS gene.

  19. Atypical haemolytic uraemic syndrome associated with a hybrid complement gene.

    Directory of Open Access Journals (Sweden)

    Julian P Venables

    2006-10-01

    Full Text Available BACKGROUND: Sequence analysis of the regulators of complement activation (RCA cluster of genes at chromosome position 1q32 shows evidence of several large genomic duplications. These duplications have resulted in a high degree of sequence identity between the gene for factor H (CFH and the genes for the five factor H-related proteins (CFHL1-5; aliases CFHR1-5. CFH mutations have been described in association with atypical haemolytic uraemic syndrome (aHUS. The majority of the mutations are missense changes that cluster in the C-terminal region and impair the ability of factor H to regulate surface-bound C3b. Some have arisen as a result of gene conversion between CFH and CFHL1. In this study we tested the hypothesis that nonallelic homologous recombination between low-copy repeats in the RCA cluster could result in the formation of a hybrid CFH/CFHL1 gene that predisposes to the development of aHUS. METHODS AND FINDINGS: In a family with many cases of aHUS that segregate with the RCA cluster we used cDNA analysis, gene sequencing, and Southern blotting to show that affected individuals carry a heterozygous CFH/CFHL1 hybrid gene in which exons 1-21 are derived from CFH and exons 22/23 from CFHL1. This hybrid encodes a protein product identical to a functionally significant CFH mutant (c.3572C>T, S1191L and c.3590T>C, V1197A that has been previously described in association with aHUS. CONCLUSIONS: CFH mutation screening is recommended in all aHUS patients prior to renal transplantation because of the high risk of disease recurrence post-transplant in those known to have a CFH mutation. Because of our finding it will be necessary to implement additional screening strategies that will detect a hybrid CFH/CFHL1 gene.

  20. Migraine, cerebrovascular disease and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Alexandra J Sinclair

    2012-01-01

    Full Text Available Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-based studies that have demonstrated that migraineurs are at increased risk of stroke outside the setting of a migraine attack have prompted the concept that migraine and cerebrovascular disease are comorbid conditions. Explanations for this association are numerous and widely debated, particularly as the comorbid association does not appear to be confined to the cerebral circulation as cardiovascular and peripheral vascular disease also appear to be comorbid with migraine. A growing body of evidence has also suggested that migraineurs are more likely to be obese, hypertensive, hyperlipidemic and have impaired insulin sensitivity, all features of the metabolic syndrome. The comorbid association between migraine and cerebrovascular disease may consequently be explained by migraineurs having the metabolic syndrome and consequently being at increased risk of cerebrovascular disease. This review will summarise the salient evidence suggesting a comorbid association between migraine, cerebrovascular disease and the metabolic syndrome.

  1. Correlations of gene expression with ratings of inattention and hyperactivity/impulsivity in tourette syndrome : a pilot study

    NARCIS (Netherlands)

    Tian, Yingfang; Stamova, Boryana; Ander, Bradley P.; Jickling, Glen C.; Gunther, Joan R.; Corbett, Blythe A.; Bos-Veneman, Netty G. P.; Hoekstra, Pieter J.; Schweitzer, Julie B.; Sharp, Frank R.

    2012-01-01

    Background: Inattentiveness, impulsivity and hyperactivity are the primary behaviors associated with attention-deficit hyperactivity disorder (ADHD). Previous studies showed that peripheral blood gene expression signatures can mirror central nervous system disease. Tourette syndrome (TS) is

  2. Down Syndrome, Obesity, Alzheimer's Disease, and Cancer: A Brief Review and Hypothesis.

    Science.gov (United States)

    Nixon, Daniel W

    2018-03-24

    Down syndrome (trisomy 21), a complex mix of physical, mental, and biochemical issues, includes an increased risk of Alzheimer's disease and childhood leukemia, a decreased risk of other tumors, and a high frequency of overweight/obesity. Certain features related to the third copy of chromosome 21 (which carries the APP gene and several anti-angiogenesis genes) create an environment favorable for Alzheimer's disease and unfavorable for cancer. This environment may be enhanced by two bioactive compounds from fat cells, leptin, and adiponectin. This paper outlines these fat-related disease mechanisms and suggests new avenues of research to reduce disease risk in Down syndrome.

  3. [Dopamine dysregulation syndrome in Parkinson's disease and restless legs syndrome].

    Science.gov (United States)

    Bayard, Sophie; Cochen De Cock, Valérie; Dauvillers, Yves

    2011-06-01

    Dopamine replacement therapy in Parkinson's disease (PD) improves the motor symptoms. However, it has recently been shown that a small sub-group of patients suffers from motor and behavioral disturbances associated with the use of dopamine agonists (DAs). The behavioral disorders are incentive- or reward-based repetitive symptoms regrouped under the term « dopamine dysregulation syndrome » (DDS). They include pathological gambling, hypersexuality, compulsive shopping, compulsive eating, punding, and compulsive medication use. Whether these behaviors are related to the dopaminergic medications interacting with an underlying individual vulnerability or whether the primary pathological features of Parkinson's disease play a role is not entirely understood. This review is devoted to the phenomenology of the DDS and factors influencing its susceptibility. We further review the literature studies that investigated the decision-making profile using the Iowa Gambling Task in Parkinson's disease, and the recent literature devoted to these abnormal behaviors in the restless legs syndrome (RLS). Given the potential substantial impact of the DDS on personal, familial, social, and financial well-being, patients with PD or RLS should be informed that DAs use may lead to the development of impulsive and compulsive disorders, and clinicians should include the investigation of these disorders as part of routine clinical care. The refinement of clinical strategies to predict, identify and manage DDS will help the future care of motor and non-motor symptoms of Parkinson's disease.

  4. WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures.

    Science.gov (United States)

    Yu, Guang; Yu, Man-li; Wang, Jia-feng; Gao, Cong-rong; Chen, Zhong-jin

    2010-10-01

    Wolfram syndrome is a rare hereditary disease characterized by diabetes mellitus and optic atrophy. The outcome of this disease is always poor. WFS1 gene mutation is the main cause of this disease. A patient with diabetes mellitus, diabetes insipidus, renal tract disorder, psychiatric abnormality, and cataract was diagnosed with Wolfram syndrome. Mutations in open reading frame (ORF) of WFS1 gene was analyzed by sequencing. Mutations in WFS1 gene was also summarized by a systematic review in Pubmed and Chinese biological and medical database. Sequencing of WFS1 gene in this patient showed a new mutation, 1962G>A, and two other non-sense mutations, 2433A>G and 2565G>A. Systematic review included 219 patients in total and identified 172 WFS1 gene mutations, most of which were located in Exon 8. These mutations in WFS1 gene might be useful in prenatal diagnosis of Wolfram syndrome.

  5. Do the MTHFR gene polymorphism and Down syndrome pregnancy ...

    African Journals Online (AJOL)

    Background: Down syndrome, the most common trisomy 21 arises from abnormal chromosomal segregation. The etiology includes genetic and acquired factors. The main genetic factor that is well appreciated for onset of Down syndrome pregnancy is MTHFR gene polymorphism. But till date, no final conclusion has arrived ...

  6. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

    OpenAIRE

    Wiseman, F.; Fisher, E.; Al_Janabi, T.; Hardy, J.; Karmiloff-Smith, Annette; Nizetic, D.; Tybulewicz, V.; Strydom, A.

    2015-01-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) — an Alzheimer disease risk factor — although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease ...

  7. Parkinson's: a syndrome rather than a disease?

    Science.gov (United States)

    Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

    2017-08-01

    Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

  8. ADAMTS-13 gene expression in antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Veysel Sabri Hançer

    2011-09-01

    Full Text Available Antiphospholipid syndrome (APS is an autoimmune disorder characterized by recurrent thrombosis and fetal mortality. Thrombotic microangiopathy (TMA is an important histological finding in catastrophic APS (CAPS and in APS patients with nephropathy. Analysis of familial thrombotic thrombocytopenic purpura patients showed that there are mutations in the ADAMTS-13 gene that lead to functional defects in the ADAMTS-13 enzyme. The aim of this study was to investigate the prevalence of the aforementioned mutations in APS, as well as to evaluate the level and activity of the ADAMTS-13 enzyme in patients with APS. C365del, Q449stop codon, P475S, and C508Y mutations were analyzed in APS patients. Transcriptions were analyzed using real-time PCR, and the level and activity of ADAMTS-13 were analyzed via fluorogenic assay. None of the mutations tested were present in the patient or control groups. The level of ADAMTS-13 mRNA in the patient group was 50% lower than that in the control group. Although a significant difference in ADAMTS-13 activity was not observed between the patient and control groups, a significant association was observed with the level of ADAMTS-13 (p<0.0001. The level and activity of ADAMTS-13 were not associated with thrombotic complications, thrombocytopenia, or pregnancy complications in the patients with APS.

  9. OBSTRUCTIVE SLEEP APNOEA SYNDROME AND CARDIOVASCULAR DISEASES

    Directory of Open Access Journals (Sweden)

    D. A. Anichkov

    2014-07-01

    Full Text Available Obstructive sleep apnoea syndrome (OSAS is observed in the population with a frequency of 5–15 %. The importance of OSAS is due to its close relationship with cardiovascular diseases. OSAS increases a risk for sudden cardiac death and is an independent predictor of chronic heart failure in males. OSAS is shown to be associated with the preclinical forms of atherosclerosis and left ventricular dysfunction.

  10. Crohn's Disease Associated with Sweet's Syndrome and Sjögren's Syndrome Treated with Infliximab

    Directory of Open Access Journals (Sweden)

    Erina N. Foster

    2005-01-01

    Full Text Available The association of Crohn's disease (CD and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions.

  11. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

    Science.gov (United States)

    Wiseman, Frances K.; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Strydom, André

    2015-01-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) — an Alzheimer disease risk factor — although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population. PMID:26243569

  12. Mitchell-Riley Syndrome: A Novel Mutation in RFX6 Gene

    Directory of Open Access Journals (Sweden)

    Marta Zegre Amorim

    2015-01-01

    Full Text Available A novel RFX6 homozygous missense mutation was identified in an infant with Mitchell-Riley syndrome. The most common features of Mitchell-Riley syndrome were present, including severe neonatal diabetes associated with annular pancreas, intestinal malrotation, gallbladder agenesis, cholestatic disease, chronic diarrhea, and severe intrauterine growth restriction. Perijejunal tissue similar to pancreatic tissue was found in the submucosa, a finding that has not been previously reported in this syndrome. This case associating RFX6 mutation with structural and functional pancreatic abnormalities reinforces the RFX6 gene role in pancreas development and β-cell function, adding information to the existent mutation databases.

  13. A novel small deletion in the NHS gene associated with Nance-Horan syndrome

    OpenAIRE

    Li, Huajin; Yang, Lizhu; Sun, Zixi; Yuan, Zhisheng; Wu, Shijing; Sui, Ruifang

    2018-01-01

    Nance-Horan syndrome is a rare X-linked recessive inherited disease with clinical features including severe bilateral congenital cataracts, characteristic facial and dental abnormalities. Data from Chinese Nance-Horan syndrome patients are limited. We assessed the clinical manifestations of a Chinese Nance-Horan syndrome pedigree and identified the genetic defect. Genetic analysis showed that 3 affected males carried a novel small deletion in NHS gene, c.263_266delCGTC (p.Ala89TrpfsTer106), a...

  14. NDRC: A Disease-Causing Genes Prioritized Method Based on Network Diffusion and Rank Concordance.

    Science.gov (United States)

    Fang, Minghong; Hu, Xiaohua; Wang, Yan; Zhao, Junmin; Shen, Xianjun; He, Tingting

    2015-07-01

    Disease-causing genes prioritization is very important to understand disease mechanisms and biomedical applications, such as design of drugs. Previous studies have shown that promising candidate genes are mostly ranked according to their relatedness to known disease genes or closely related disease genes. Therefore, a dangling gene (isolated gene) with no edges in the network can not be effectively prioritized. These approaches tend to prioritize those genes that are highly connected in the PPI network while perform poorly when they are applied to loosely connected disease genes. To address these problems, we propose a new disease-causing genes prioritization method that based on network diffusion and rank concordance (NDRC). The method is evaluated by leave-one-out cross validation on 1931 diseases in which at least one gene is known to be involved, and it is able to rank the true causal gene first in 849 of all 2542 cases. The experimental results suggest that NDRC significantly outperforms other existing methods such as RWR, VAVIEN, DADA and PRINCE on identifying loosely connected disease genes and successfully put dangling genes as potential candidate disease genes. Furthermore, we apply NDRC method to study three representative diseases, Meckel syndrome 1, Protein C deficiency and Peroxisome biogenesis disorder 1A (Zellweger). Our study has also found that certain complex disease-causing genes can be divided into several modules that are closely associated with different disease phenotype.

  15. Muir-Torre Syndrome: A Case Associated with an Infrequent Gene Mutation.

    Science.gov (United States)

    Grob, Alexandra; Feser, Christina; Grekin, Steven

    2016-01-01

    Muir-Torre syndrome is a rare, autosomal dominant genodermatosis characterized by the presence of at least one sebaceous gland neoplasm, associated with an underlying visceral malignancy. Muir-Torre syndrome is believed to be a subtype of Lynch Syndrome. Affected individuals are found to have germline mutations predominantly in DNA mismatch repair gene MSH2, and much less frequently, MLH1. The authors report the case of a 55-year-old woman presenting with multiple cutaneous neoplasms including sebaceoma, basal cell carcinoma, and squamous cell carcinoma; personal history of colorectal and endometrial cancer; and family history of colorectal cancer; found to have a deletion at mismatch repair gene MLH1. It is important to recognize the role of these less common gene deletions in producing the Muir-Torre syndrome phenotype, and consider the correlation of cutaneous manifestations with internal disease. The authors discuss the clinical presentation of Muir-Torre syndrome, methods of diagnosis, and the importance of regular medical surveillance to detect and prevent disease progression in Muir-Torre syndrome patients and their family members.

  16. Role of genes in oro-dental diseases

    Directory of Open Access Journals (Sweden)

    Kavitha B

    2010-01-01

    Full Text Available In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late, significant progress has been made in the molecular analysis of tumors. With molecular genetic testing emerging as diagnostic, prognostic, and therapeutic approach, a review of genetic alterations ranging from the development of oro-facial structures to the tumors in the head and neck region are addressed in this article. The functional regulatory aspect of genes in relation to oro-facial structures are discussed separately, i.e., in relation to tooth genesis, tooth agenesis (non-syndromic, syndromic, tooth structural alterations, syndromic oro-facial defects, bone diseases, skin diseases (genodermatoses, and malignant tumors. In this literature, various genes involved in the development of the oro-facial structures and tooth in particular are discussed. The genetic basis of disorders in the tooth development (agenesis, hypodontia, tooth structural defects like amelogenesis imperfecta (AI, dentinogenesis imperfecta (DI, and oro-facial structural alterations (various syndromes are explained.

  17. Moyamoya disease and syndromes: from genetics to clinical management

    Directory of Open Access Journals (Sweden)

    Guey S

    2015-02-01

    . Revascularization surgery can be indicated, with several techniques. Characteristics of genetic moyamoya syndromes are presented, with a focus on recently reported mutations in BRCC3/MTCP1 and GUCY1A3 genes. Identification of the genes involved in moyamoya disease and several monogenic moyamoya syndromes unraveled different pathways involved in the development of this angiopathy. Studying genes and pathways involved in monogenic moyamoya syndromes may help to give insights into pathophysiological models and discover potential candidates for medical treatment strategies. Keywords: moyamoya disease, moyamoya syndrome, stroke, surgical revascularization, genetics

  18. Gene transfer therapy in vascular diseases.

    Science.gov (United States)

    McKay, M J; Gaballa, M A

    2001-01-01

    Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of

  19. Congenital Heart Diseases associated with Identified Syndromes ...

    African Journals Online (AJOL)

    Recognised syndromes were seen in 69(68%) cases. Down syndrome with 54 children contributed 78.3% of those with known syndromes. Other identified syndromes and associations were Marfan's, Noonan's, Edwards, Prune Belly, Apert, Ellis-van creveld syndrome and congenital rubella syndrome. Congenital heart ...

  20. Primary progressive aphasia: from syndrome to disease.

    Science.gov (United States)

    Matías-Guiu, J A; García-Ramos, R

    2013-01-01

    Primary progressive aphasia (PPA) is a clinical syndrome characterised by a progressive decline in language and speech of neurodegenerative origin. Major breakthroughs made in recent years have lent us a better understanding of this syndrome, which may be the first manifestation of any of a number of neurodegenerative diseases. We reviewed the main aspects of PPA epidemiology, clinical manifestations, diagnosis, aetiology and treatment. Most cases manifest sporadically and the typical age of onset is between 50 and 70 years. Three clinically distinct variants have been described: nonfluent or agrammatic PPA, semantic PPA and logopenic PPA. Each of these variants tends to be associated with specific histopathological findings, but clinical diagnostic methods are imperfect predictors of underlying pathology. Anatomical and functional neuroimaging can provide useful biomarkers. Several treatments have been proposed, and while no clear benefits have been demonstrated, acetylcholinesterase inhibitors may be useful, especially in the logopenic variant. PPA is an emerging syndrome which may be more prevalent than we might expect. It was previously listed as part of the frontotemporal dementia spectrum, and it is also related to Alzheimer disease. Clinical diagnosis, complemented by a biomarker evaluation, may predict the underlying pathology, which in turn will improve treatment possibilities. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  1. Capgras syndrome and its relationship to neurodegenerative disease.

    Science.gov (United States)

    Josephs, Keith A

    2007-12-01

    Capgras syndrome is characterized by a delusional belief that a person has been replaced by an imposter. It has been described in psychiatric and neurological (neurodegenerative and nonneurodegenerative) diseases. To determine whether the clinical and demographic features of subjects with Capgras syndrome differ when the syndrome is associated with neurodegenerative compared with nonneurodegenerative diseases, and whether features differ across different neurodegenerative diseases. Retrospective study. Tertiary care medical center. Patients Forty-seven subjects with Capgras syndrome. Thirty-eight of the subjects with Capgras syndrome (81%) had a neurodegenerative disease, most commonly Lewy body disease. Capgras syndrome occurred at a younger age of onset in those with a nonneurodegenerative disease (51 vs 72 years) (P Capgras syndrome and Lewy body disease, 100% had visual hallucinations compared with only one of those with Alzheimer disease (14%). Capgras syndrome is more commonly associated with neurodegenerative diseases, especially Lewy body disease, where visual hallucinations always coexist. In the absence of a neurodegenerative disease, the onset of Capgras syndrome occurs at a significantly younger age and can be associated with psychiatric disease, cerebrovascular events, and illicit drug use.

  2. Pearson syndrome in an infant heterozygous for C282Y allele of HFE gene.

    Science.gov (United States)

    Kefala-Agoropoulou, Kalomoira; Roilides, Emmanuel; Lazaridou, Anna; Karatza, Eliza; Farmaki, Evangelia; Tsantali, Haido; Augoustides-Savvopoulou, Persephone; Tsiouris, John

    2007-12-01

    Pearson syndrome is a rare mitochondrial disorder characterized by sideroblastic anemia, liver disease, renal tubulopathy and exocrine pancreas deficiency. We describe a female infant suffering from anemia since birth who gradually developed the complete picture of Pearson syndrome by 13 months. Iron overload was disproportionate to blood transfusions. The patient was heterozygous for HFE gene C282Y mutation (type I hemochromatosis). After an initial response to deferoxamine she presented with cutaneous zygomycosis and died after metabolic derangement and Pneumocystis jiroveci pneumonia. This is the second case of a Pearson syndrome individual who was also heterozygous for HFE gene mutation C282Y published. It is also the second case report of a Pearson patient suffering from severe iron overload and liver disease that responded to therapy with deferoxamine.

  3. Nance-Horan syndrome: a contiguous gene syndrome involving deletion of the amelogenin gene? A case report and molecular analysis.

    Science.gov (United States)

    Franco, E; Hodgson, S; Lench, N; Roberts, G J

    1995-03-01

    A case of Nance-Horan syndrome in a male is presented, with some features of the condition in his carrier mother and her mother. It is proposed that Nance-Horan syndrome might be a contiguous gene syndrome mapping to chromosome Xp21.2-p22.3. The proband had congenital cataract microphthalmia and dental abnormalities including screwdriver shaped incisors and evidence of enamel pitting hypoplasia. The region Xp21.2-p22.3 also contains the tooth enamel protein gene, amelogenin (AMGX). Using molecular genetic techniques, we have shown that there is no evidence that the AMGX gene is deleted in this case of the Nance-Horan syndrome.

  4. WFS1/wolframin mutations, Wolfram syndrome, and associated diseases.

    Science.gov (United States)

    Khanim, F; Kirk, J; Latif, F; Barrett, T G

    2001-05-01

    Wolfram syndrome (WS) is the inherited association of juvenile-onset insulin-dependant diabetes mellitus and progressive bilateral optic atrophy. A nuclear gene, WFS1/wolframin, was identified that segregated with disease status and demonstrated an autosomal recessive mode of inheritance. Mutation analysis of the WFS1 gene in WS patients has identified mutations in 90% of patients. Most were compound heterozygotes with private mutations distributed throughout the gene with no obvious hotspots. The private nature of the mutations in WS patients and the low frequencies make it difficult to determine the biological or clinical relevance of these mutations. Mutation screening in patients with psychiatric disorders or diabetes mellitus has also been performed to test the hypothesis that heterozygous carriers of WFS1 gene mutations are at an increased risk following the observation that WS first-degree relatives have a higher frequency of these disorders. Most studies showed no association, however two missense mutations were identified that demonstrated significant association with psychiatric disorders and diabetes mellitus. Population association studies and functional studies of these variants will need to be performed to confirm these preliminary results. The elucidation of functions and functional pathways for the WFS1 gene product and variants will shed light on the effect of such disparate mutations on gene function and their role in the resulting clinical phenotype in WS and associated disorders. Copyright 2001 Wiley-Liss, Inc.

  5. Acute Respiratory Distress: from syndrome to disease.

    Science.gov (United States)

    Cardinal-Fernández, P; Correger, E; Villanueva, J; Rios, F

    2016-04-01

    The acute respiratory distress syndrome (ARDS) is currently one of the most important critical entities given its high incidence, rate of mortality, long-term sequelae and non-specific pharmacological treatment. The histological hallmark of ARDS is diffuse alveolar damage (DAD). Approximately 50% of ARDS patients present DAD, the rest is made up of a heterogeneous group of histological patterns, many of which correspond to a well-recognized disease. For that reason, if these patterns could be diagnosed, patients could benefit from a treatment. Recently, the effect of DAD in clinical and analytical evolution of ARDS has been demonstrated, so the classical approach to ARDS as an entity defined solely by clinical, radiological and gasometrical variables should be reconsidered. This narrative review aims to examine the need to evolve from the concept of ARDS as a syndrome to ARDS as a specific disease. So we have raised 4 critical questions: a) What is a disease?; b) what is DAD?; c) how is DAD considered according to ARDS definition?, and d) what is the relationship between ARDS and DAD? Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  6. Huntington's disease and Huntington's disease-like syndromes: an overview.

    Science.gov (United States)

    Gövert, Felix; Schneider, Susanne A

    2013-08-01

    The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's disease-like (HDL) phenotypes. To familiarize clinicians with these (in some cases very rare) conditions we will summarize the main characteristics. HDL disorders are rare and account for about 1% of cases presenting with a Huntington's disease phenotype. They share overlapping clinical features, so making the diagnosis purely on clinical grounds may be challenging, however presence of certain characteristics may be a clue (e.g. prominent orofacial involvement in neuroferritinopathy etc.), Information of ethnic descent will also guide genetic work-up [HDL2 in Black Africans; dentatorubral-pallidoluysian atrophy (DRPLA) in Japanese etc.], Huntington's disease, the classical HDL disorders (except HDL3) and DRPLA are repeat disorders with anticipation effect and age-dependent phenotype in some, but genetic underpinnings may be more complicated in the other chorea syndromes. With advances in genetics more and more rare diseases are disentangled, allowing molecular diagnoses in a growing number of choreic patients. Hopefully, with better understanding of their pathophysiology we are moving towards mechanistic therapies.

  7. Gene therapy for sickle cell disease.

    Science.gov (United States)

    Olowoyeye, Abiola; Okwundu, Charles I

    2016-11-14

    Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. The objectives of this review are:to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 August 2016. All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. No trials of gene therapy for sickle cell disease were found. No trials of gene therapy for sickle cell disease were reported. No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

  8. Restless legs syndrome associated with major diseases

    Science.gov (United States)

    Allen, Richard; Högl, Birgit; Paulus, Walter

    2016-01-01

    Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene–microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other. PMID:26944272

  9. Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

    Science.gov (United States)

    Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

    2014-10-01

    Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc

  10. Turner′s syndrome presenting as metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Sadishkumar Kamalanathan

    2012-01-01

    Full Text Available Turner′s syndrome is a genetic disorder with a complete or partial absence of one X chromosome with characteristic phenotypic features. The prevalence of renal anomalies in turner syndrome is 30-40%. However, the renal function is usually normal. We report a case of Turner′s syndrome presenting with chronic kidney disease and renal osteodystrophy.

  11. Angelman Syndrome Due to UBE3A Gene Mutation.

    Science.gov (United States)

    Goswami, Jyotindra Narayan; Sahu, Jitendra Kumar; Singhi, Pratibha

    2017-12-18

    A 12-y-old boy presented with developmental delay, autism, epilepsy, limb tremors and behavioral problems which posed a diagnostic challenge. Though his clinical profile and electroencephalogram were suggestive of Angelman syndrome, initial genetic tests were unyielding. Exome sequencing revealed a previously unreported mutation of Ubiquitin Protein Ligase E3A (UBE3A) gene, confirming the diagnosis of Angelman syndrome. The case is aimed to sensitize pediatricians about Angelman syndrome and to highlight the role of sequential investigations in establishing the diagnosis.

  12. Exclusion of RAI2 as the causative gene for Nance-Horan syndrome.

    Science.gov (United States)

    Walpole, S M; Ronce, N; Grayson, C; Dessay, B; Yates, J R; Trump, D; Toutain, A

    1999-05-01

    Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, microphthalmia and/or microcornea, unusual dental morphology, dysmorphic facial features, and developmental delay in some cases. Recent linkage studies have mapped the NHS disease gene to a 3.5-cM interval on Xp22.2 between DXS1053 and DXS443. We previously identified a human homologue of a mouse retinoic-acid-induced gene (RAI2) within the NHS critical flanking interval and have tested the gene as a candidate for Nance-Horan syndrome in nine NHS-affected families. Direct sequencing of the RAI2 gene and predicted promoter region has revealed no mutations in the families screened; RAI2 is therefore unlikely to be associated with NHS.

  13. Gene2DisCo: Gene to disease using disease commonalities.

    Science.gov (United States)

    Frasca, Marco

    2017-10-01

    Finding the human genes co-causing complex diseases, also known as "disease-genes", is one of the emerging and challenging tasks in biomedicine. This process, termed gene prioritization (GP), is characterized by a scarcity of known disease-genes for most diseases, and by a vast amount of heterogeneous data, usually encoded into networks describing different types of functional relationships between genes. In addition, different diseases may share common profiles (e.g. genetic or therapeutic profiles), and exploiting disease commonalities may significantly enhance the performance of GP methods. This work aims to provide a systematic comparison of several disease similarity measures, and to embed disease similarities and heterogeneous data into a flexible framework for gene prioritization which specifically handles the lack of known disease-genes. We present a novel network-based method, Gene2DisCo, based on generalized linear models (GLMs) to effectively prioritize genes by exploiting data regarding disease-genes, gene interaction networks and disease similarities. The scarcity of disease-genes is addressed by applying an efficient negative selection procedure, together with imbalance-aware GLMs. Gene2DisCo is a flexible framework, in the sense it is not dependent upon specific types of data, and/or upon specific disease ontologies. On a benchmark dataset composed of nine human networks and 708 medical subject headings (MeSH) diseases, Gene2DisCo largely outperformed the best benchmark algorithm, kernelized score functions, in terms of both area under the ROC curve (0.94 against 0.86) and precision at given recall levels (for recall levels from 0.1 to 1 with steps 0.1). Furthermore, we enriched and extended the benchmark data to the whole human genome and provided the top-ranked unannotated candidate genes even for MeSH disease terms without known annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Fragile X syndrome: An overview and update of the FMR1 gene.

    Science.gov (United States)

    Mila, M; Alvarez-Mora, M I; Madrigal, I; Rodriguez-Revenga, L

    2018-02-01

    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and the leading form of the monogenic cause of autism. Fragile X mental retardation type 1 (FMR1) gene premutation is the first single-gene cause of primary ovarian failure (Fragile X-associated primary ovarian insufficiency [FXPOI]) and one of the most common causes of ataxia (fragile X-associated tremor/ataxia syndrome [FXTAS]), multiple additional phenotypes such as fibromyalgia, hypothyroidism, migraine headaches, sleep disturbances, sleep apnea, restless legs syndrome, central pain syndrome, neuropathy and neuropsychiatric alterations has been described. Clinical involvement in men and women carrying the FMR1 premutation currently constitutes a real health problem in the society that should be taken into account. It is important to highlight that while in FXS there is a loss-of-function of the FMR1 gene, in premutation associated disorders there is a gain of FMR1 mRNA function. To date, the tremendous progress achieved in the understanding of the pathophysiology of FXS, has led to the development of several targeted therapies aimed at preventing or improving the neurological manifestations of the disease. This review is an update of the diseases associated with the FMR1 gene. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    ) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant......A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...... immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes...

  16. A Pediatric Case of Cowden Syndrome with Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Cláudia Patraquim

    2017-01-01

    Full Text Available Cowden syndrome (CS is a rare dominantly inherited multisystem disorder, characterized by an extraordinary malignant potential. In 80% of cases, the human tumor suppressor gene phosphatase and tensin homolog (PTEN is mutated. We present a case of a 17-year-old boy with genetically confirmed CS and Graves’ disease (GD. At the age of 15, he presented with intention tremor, palpitations, and marked anxiety. On examination, he had macrocephaly, coarse facies, slight prognathism, facial trichilemmomas, abdominal keratoses, leg hemangioma, and a diffusely enlarged thyroid gland. He started antithyroid drug (ATD therapy with methimazole and, after a 2-year treatment period without achieving a remission status, a total thyroidectomy was performed. Diagnosis and management of CS should be multidisciplinary. Thyroid disease is frequent, but its management has yet to be fully defined. The authors present a case report of a pediatric patient with CS and GD and discuss treatment options.

  17. Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes.

    Science.gov (United States)

    Keegan, Catherine E; Hutz, Janna E; Krause, Andrea S; Koehler, Katrin; Metherell, Louise A; Boikos, Sosipatros; Stergiopoulos, Sotirios; Clark, Adrian J L; Stratakis, Constantine A; Huebner, Angela; Hammer, Gary D

    2007-08-01

    ACTH resistance is a feature of several human syndromes with known genetic causes, including familial glucocorticoid deficiency (types 1 and 2) and triple A syndrome. However, many patients with ACTH resistance lack an identifiable genetic aetiology. The human homolog of the Acd gene, mutated in a mouse model of adrenal insufficiency, was sequenced in 25 patients with a clinical diagnosis of familial glucocorticoid deficiency or triple A syndrome. A 3.4 kilobase genomic fragment containing the entire ACD gene was analysed for mutations in all 25 patients. Samples were obtained by three investigators from different institutions. The primary cohort consisted of 25 unrelated patients, primarily of European or Middle Eastern descent, with a clinical diagnosis of either familial glucocorticoid deficiency (FGD) or triple A syndrome. Patients lacked mutations in other genes known to cause ACTH resistance, including AAAS for patients diagnosed with triple A syndrome and MC2R and MRAP for patients diagnosed with familial glucocorticoid deficiency. Thirty-five additional patients with adrenal disease phenotypes were added to form an expanded cohort of 60 patients. Identification of DNA sequence changes in the ACD gene in the primary cohort and analysis of putative ACD haplotypes in the expanded cohort. No disease-causing mutations were found, but several novel single nucleotide polymorphisms (SNPs) and two putative haplotypes were identified. The overall frequency of SNPs in ACD is low compared to other gene families. No mutations were identified in ACD in this collection of patients with ACTH resistance phenotypes. However, the newly identified SNPs in ACD should be more closely examined for possible links to disease.

  18. Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease.

    Science.gov (United States)

    Tatsi, Christina; Stratakis, Constantine A

    2018-03-01

    Neonatal Cushing syndrome (CS) is most commonly caused by exogenous administration of glucocorticoids and rarely by endogenous hypercortisolemia. CS owing to adrenal lesions is the most common cause of endogenous CS in neonates and infants, and adrenocortical tumors (ACTs) represent most cases. Many ACTs develop in the context of a TP53 gene mutation, which causes Li-Fraumeni syndrome. More rarely, neonatal CS presents as part of other syndromes such as McCune-Albright syndrome or Beckwith-Wiedemann syndrome. Management usually includes resection of the primary tumor with or without additional medical treatment, but manifestations may persist after resolution of hypercortisolemia. Published by Elsevier Inc.

  19. Robust gene dysregulation in Alzheimer's disease brains.

    Science.gov (United States)

    Feng, Xuemei; Bai, Zhouxian; Wang, Jiajia; Xie, Bin; Sun, Jiya; Han, Guangchun; Song, Fuhai; Crack, Peter J; Duan, Yong; Lei, Hongxing

    2014-01-01

    The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation. Based on this observation, we selected 100 genes with the highest frequency of dysregulation to illustrate the core perturbation in AD brains. The dysregulation of these genes was validated in several independent datasets for AD. We further identified 12 genes with strong correlation of gene expression with disease progression. The relevance of these genes to disease progression was also validated in an independent dataset. Interestingly, we found a transcriptional "cushion" for these 100 genes in the less vulnerable visual cortex region, which may be a critical component of the protection mechanism for less vulnerable brain regions. To facilitate the research in this field, we have provided the expression information of ~8000 relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn).

  20. Diagnostic test for prenatal identification of Down's syndrome and mental retardation and gene therapy therefor

    Science.gov (United States)

    Smith, Desmond J.; Rubin, Edward M.

    2000-01-01

    A a diagnostic test useful for prenatal identification of Down syndrome and mental retardation. A method for gene therapy for correction and treatment of Down syndrome. DYRK gene involved in the ability to learn. A method for diagnosing Down's syndrome and mental retardation and an assay therefor. A pharmaceutical composition for treatment of Down's syndrome mental retardation.

  1. KATP channels and cardiovascular disease: suddenly a syndrome.

    Science.gov (United States)

    Nichols, Colin G; Singh, Gautam K; Grange, Dorothy K

    2013-03-29

    ATP-sensitive potassium (KATP) channels were first discovered in the heart 30 years ago. Reconstitution of KATP channel activity by coexpression of members of the pore-forming inward rectifier gene family (Kir6.1, KCNJ8, and Kir6.2 KCNJ11) with sulfonylurea receptors (SUR1, ABCC8, and SUR2, ABCC9) of the ABCC protein subfamily has led to the elucidation of many details of channel gating and pore properties. In addition, the essential roles of Kir6.x and SURx subunits in generating cardiac and vascular KATP(2) and the detrimental consequences of genetic deletions or mutations in mice have been recognized. However, despite this extensive body of knowledge, there has been a paucity of defined roles of KATP subunits in human cardiovascular diseases, although there are reports of association of a single Kir6.1 variant with the J-wave syndrome in the ECG, and 2 isolated studies have reported association of loss of function mutations in SUR2 with atrial fibrillation and heart failure. Two new studies convincingly demonstrate that mutations in the SUR2 gene are associated with Cantu syndrome, a complex multi-organ disorder characterized by hypertrichosis, craniofacial dysmorphology, osteochondrodysplasia, patent ductus arteriosus, cardiomegaly, pericardial effusion, and lymphoedema. This realization of previously unconsidered consequences provides significant insight into the roles of the KATP channel in the cardiovascular system and suggests novel therapeutic possibilities.

  2. Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

    Science.gov (United States)

    Lagerstedt-Robinson, Kristina; Rohlin, Anna; Aravidis, Christos; Melin, Beatrice; Nordling, Margareta; Stenmark-Askmalm, Marie; Lindblom, Annika; Nilbert, Mef

    2016-11-01

    Lynch syndrome caused by constitutional mismatch‑repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2. After 20 years of genetic counseling and genetic testing for Lynch syndrome, we have compiled the mutation spectrum in Sweden with the aim to provide a population-based perspective on the contribution from the different MMR genes, the various types of mutations and the influence from founder mutations. Mutation data were collected on a national basis from all laboratories involved in genetic testing. Mutation analyses were performed using mainly Sanger sequencing and multiplex ligation-dependent probe amplification. A total of 201 unique disease-predisposing MMR gene mutations were identified in 369 Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder mutation that accounted for 15% of the families with mutations in MLH1. In conclusion, the Swedish Lynch syndrome mutation spectrum is diverse with private MMR gene mutations in two-thirds of the families, has a significant contribution from internationally recognized mutations and a limited effect from founder mutations.

  3. Steven Johnson syndrome in a patient with Cushing's disease.

    Science.gov (United States)

    Mustafa, N; Periyasamy, P; Kamaruddin, N

    2009-09-01

    Cushing's syndrome is a pathological condition associated with excessive cortisol production, the commonest etiology being Cushing's disease. Corticosteroids in high doses have been used in the management of Steven Johnson Syndrome (SJS) with favourable outcome. We describe a patient with Cushing's disease who developed SJS, one week after taking sperulina a product from sea-weed while waiting for transphenoidal surgery.

  4. Marfan syndrome gene search intensifies following identification of basic defect

    Energy Technology Data Exchange (ETDEWEB)

    Randall, T.

    1990-10-03

    Somewhere, quite possible along chromosomes 8 and/or 15, the gene(s) for Marfan syndrome will be found. The search is intensifying following a report that faulty scaffolding in the body's connective tissue appears to be the long sought after defect behind the syndrome, and inherited disorder that has caused the premature death of young, healthy-looking individuals. Finding that something in the living masonry of the human body has proven to be a 30-year inquisition of nearly two dozen molecules that has engaged investigators worldwide. Historically, researchers have searched for a structural flaw in one of the collagen molecules to explain the cause of Marfan Syndrome. Using monoclonal antibodies, researchers have implicated microfibrils, the extracellular filaments that provide a matrix for the deposit of elastin during embryonic development.

  5. Single Gene and Syndromic Causes of Obesity: Illustrative Examples.

    Science.gov (United States)

    Butler, Merlin G

    2016-01-01

    Obesity is a significant health problem in westernized societies, particularly in the United States where it has reached epidemic proportions in both adults and children. The prevalence of childhood obesity has doubled in the past 30 years. The causation is complex with multiple sources, including an obesity promoting environment with plentiful highly dense food sources and overall decreased physical activity noted for much of the general population, but genetic factors clearly play a role. Advances in genetic technology using candidate gene approaches, genome-wide association studies, structural and expression microarrays, and next generation sequencing have led to the discovery of hundreds of genes recognized as contributing to obesity. Polygenic and monogenic causes of obesity are now recognized including dozens of examples of syndromic obesity with Prader-Willi syndrome, as a classical example and recognized as the most common known cause of life-threatening obesity. Genetic factors playing a role in the causation of obesity will be discussed along with the growing evidence of single genes and the continuum between monogenic and polygenic obesity. The clinical and genetic aspects of four classical but rare obesity-related syndromes (ie, Prader-Willi, Alström, fragile X, and Albright hereditary osteodystrophy) will be described and illustrated in this review of single gene and syndromic causes of obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Kallmann syndrome and ichthyosis: a case of contiguous gene deletion syndrome

    Directory of Open Access Journals (Sweden)

    Irene Berges-Raso

    2017-09-01

    Full Text Available Kallmann syndrome is a genetically heterogeneous form of hypogonadotropic hypogonadism caused by gonadotropin-releasing hormone deficiency and characterized by anosmia or hyposmia due to hypoplasia of the olfactory bulbs; osteoporosis and metabolic syndrome can develop due to longstanding untreated hypogonadism. Kallmann syndrome affects 1 in 10 000 men and 1 in 50 000 women. Defects in 17 genes, including KAL1, have been implicated. Kallmann syndrome can be associated with X-linked ichthyosis, a skin disorder characterized by early onset dark, dry, irregular scales affecting the limb and trunk, caused by a defect of the steroid sulfatase gene (STS. Both KAL1 and STS are located in the Xp22.3 region; therefore, deletions in this region cause a contiguous gene syndrome. We report the case of a 32-year-old man with ichthyosis referred for evaluation of excessive height (2.07 m and weight (BMI: 29.6 kg/m2, microgenitalia and absence of secondary sex characteristics. We diagnosed Kallmann syndrome with ichthyosis due to a deletion in Xp22.3, a rare phenomenon.

  7. Candidate gene association studies in syndromic and non-syndromic cleft lip and palate

    Energy Technology Data Exchange (ETDEWEB)

    Daack-Hirsch, S.; Basart, A.; Frischmeyer, P. [Univ. of Iowa, IA (United States)] [and others

    1994-09-01

    Using ongoing case ascertainment through a birth defects registry, we have collected 219 nuclear families with non-syndromic cleft lip and/or palate and 111 families with a collection of syndromic forms. Syndromic cases include 24 with recognized forms and 72 with unrecognized syndromes. Candidate gene studies as well as genome-wide searches for evidence of microdeletions and isodisomy are currently being carried out. Candidate gene association studies, to date, have made use of PCR-based polymorphisms for TGFA, MSX1, CLPG13 (a CA repeat associated with a human homologue of a locus that results in craniofacial dysmorphogenesis in the mouse) and an STRP found in a Van der Woude syndrome microdeletion. Control tetranucleotide repeats, which insure that population-based differences are not responsible for any observed associations, are also tested. Studies of the syndromic cases have included the same list of candidate genes searching for evidence of microdeletions and a genome-wide search using tri- and tetranucleotide polymorphic markers to search for isodisomy or structural rearrangements. Significant associations have previously been identified for TGFA, and, in this report, identified for MSX1 and nonsyndromic cleft palate only (p = 0.04, uncorrected). Preliminary results of the genome-wide scan for isodisomy has returned no true positives and there has been no evidence for microdeletion cases.

  8. Celiac disease in siblings with Pearson syndrome.

    Science.gov (United States)

    Köklü, Seyfettin; Alioğlu, Bülent; Akbal, Erdem; Koçak, Erdem

    2010-04-01

    Pearson syndrome (PS) is a rare mitochondrial disorder characterized by sideroblastic anemia and exocrine pancreas deficiency as a result of mitochondrial DNA deletion or deletion-duplication. A 21-year-old woman and 11-year-old brother who had been diagnosed as PS at the age of 18 and 8, respectively, were admitted to our hospital with the complaints of chronic diarrhea while using exogenous pancreas enzymes. Diarrhea was present in both for a long time and attributed to existing PS. Endoscopic and laboratory examinations revealed celiac disease (CD). After gluten-free diet, their symptoms were resolved. Detailed family investigation revealed that parents and the sister of the siblings were free of both PS and CD. To our knowledge, there has been no previous report of the presence of these 2 disorders, PS and CD, in the same patient. CD should be screened and treated appropriately in cases with PS.

  9. Gitelman syndrome : consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

    NARCIS (Netherlands)

    Blanchard, Anne; Bockenhauer, Detlef; Bolignano, Davide; Calò, Lorenzo A; Cosyns, Etienne; Devuyst, Olivier; Ellison, David H; Karet Frankl, Fiona E; Knoers, Nine V A M; Konrad, Martin; Lin, Shih-Hua; Vargas-Poussou, Rosa

    Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride

  10. Is irritable bowel syndrome an infectious disease?

    Science.gov (United States)

    Thompson, John Richard

    2016-01-28

    Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms.

  11. The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16

    Energy Technology Data Exchange (ETDEWEB)

    Polymeropoulos, M.H.; Ide, S.E. [National Institute of Health, Bethesda, MD (United States); Wright, M. [Univ. of Newcastle Upon Tyne (United Kingdom)] [and others

    1996-07-01

    Ellis-van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by disproportionate dwarfism, polydactyly, and congenital heart disease. This rare disorder is found with increased frequency among the Old Order Amish community in Lancaster County, Pennsylvania. We have used linkage analysis to localize the gene responsible for the EVC phenotype in nine interrelated Amish pedigrees and three unrelated families from Mexico, Ecuador, and Brazil. We now report the linkage for the Ellisvan Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Z{sub max} = 6.91 at {theta} = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype. 17 refs., 2 figs., 1 tab.

  12. Prospects for Gene Therapy in the Fragile X Syndrome

    Science.gov (United States)

    Rattazzi, Mario C.; LaFauci, Giuseppe; Brown, W. Ted

    2004-01-01

    Gene therapy is unarguably the definitive way to treat, and possibly cure, genetic diseases. A straightforward concept in theory, in practice it has proven difficult to realize, even when directed to easily accessed somatic cell systems. Gene therapy for diseases in which the central nervous system (CNS) is the target organ presents even greater…

  13. Parkinson's disease and mitochondrial gene variations

    DEFF Research Database (Denmark)

    Andalib, Sasan; Vafaee, Manouchehr Seyedi; Gjedde, Albert

    2014-01-01

    Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochondrial gene variations and mutations as well as from nuclear gene variations...

  14. What can we learn from study of Alzheimer's disease in patients with Down syndrome for early-onset Alzheimer's disease in the general population?

    OpenAIRE

    Wallace, Robyn A; Dalton, Arthur J

    2011-01-01

    The clinical and scientific study of dementia in adults with Down syndrome led to the development of the amyloid hypothesis as a fundamental concept in Alzheimer's disease pathogenesis. The journey started with the discovery of the structure and metabolic processing of ?-amyloid brain deposits associated with Alzheimer's dementia in adults with Down syndrome, and then the prediction and confirmation of the amyloid precursor protein gene on chromosome 21. The processes and genes responsible fo...

  15. Identification of gene networks and pathways associated with Guillain-Barre syndrome.

    Directory of Open Access Journals (Sweden)

    Kuo-Hsuan Chang

    Full Text Available BACKGROUND: The underlying change of gene network expression of Guillain-Barré syndrome (GBS remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. METHODS AND FINDINGS: Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05. FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. CONCLUSIONS: This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies.

  16. An R1632C variant in the SCN5A gene causing Brugada syndrome.

    Science.gov (United States)

    García-Molina, Esperanza; Sabater-Molina, María; Muñoz, Carmen; Ruiz-Espejo, Francisco; Gimeno, Juan R

    2016-06-01

    Brugada syndrome (BS) is an electrical disease, inherited in an autosomal dominant manner. BS is caused by mutations in up to 13 different genes. SCN5A is the gene most frequently mutated in BS, although this presents an incomplete penetrance. The present case study investigated the SCN5A gene in a family exhibiting BS. Direct sequencing of the SCN5A gene was performed to identify mutations and a familial investigation was performed. A novel variant was identified in the voltage‑sensing domain of the SCN5A protein. This familial investigation revealed one novel asymptomatic carrier in the family. Genetic investigations are useful to classify individuals who require more frequent clinical monitoring and to stratify the risk of developing the disease.

  17. Gene therapy for CNS diseases – Krabbe disease

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2016-06-01

    Full Text Available This is a brief report of the 19th Annual Meeting of the American Society of Gene and Cell Therapy that took place from May 4th through May 7th, 2016 in Washington, DC, USA. While the meeting provided many symposiums, lectures, and scientific sessions this report mainly focuses on one of the sessions on the "Gene Therapy for central nervous system (CNS Diseases" and specifically on the "Gene Therapy for the globoid cell leukodystrophy or Krabbe disease. Two presentations focused on this subject utilizing two animal models of this disease: mice and dog models. Different serotypes of adeno-associate viral vectors (AAV alone or in combination with bone marrow transplantations were used in these research projects. The Meeting of the ASGCT reflected continuous growth in the fields of gene and cell therapy and brighter forecast for efficient treatment options for variety of human diseases.

  18. Capgras Syndrome in Advanced Parkinson's Disease.

    Science.gov (United States)

    Groth, Christopher L; Pusso, Antonia; Sperling, Scott A; Huss, Diane S; Elias, W Jeffrey; Wooten, G Frederick; Barrett, Matthew J

    2017-11-14

    Psychosis is common in Parkinson's disease (PD), especially in advanced disease, and can lead to a number of psychotic symptoms, including delusions. One uncommon delusion is Capgras syndrome (CS). The authors report on three PD patients with a history of deep brain stimulation (DBS) who developed this delusion. The anatomic targets in these three patients were the subthalamic nuclei in two patients and the globus pallidus interna in one patient. The length of time between surgery and development of CS varied but was greater than 6 months. Additionally, all three patients showed evidence of impaired cognition prior to development of CS. Therefore, due to the length of time between DBS and CS in all three cases and the fact that one patient developed CS months after DBS explanation, DBS does not appear to be associated with CS. Given the distressing nature of this condition, patients with advanced PD who undergo DBS should be regularly screened for symptoms of psychosis with awareness of CS as a potential form.

  19. Treacher Collins Syndrome: the genetics of a craniofacial disease.

    Science.gov (United States)

    Kadakia, Sameep; Helman, Samuel N; Badhey, Arvind K; Saman, Masoud; Ducic, Yadranko

    2014-06-01

    The molecular underpinnings of Treacher Collins Syndrome (TCS) are diverse. This article codifies the most recent findings in this complex area of research to further current understanding of the disease process. Elucidating the genetic causes of the disorder can be useful in earlier detection and better treatment planning. Articles from 1991 to 2013 were selected and reviewed by five researchers utilizing the most recent literature of the genetics and pathophysiology of TCS. Mutations in TCOF1, POLR1C and POLR1D have all been implicated in causing TCS. The association of the TCOF1 gene product, Treacle, and gene products of POLR1C and POLR1D with ribosome biosynthesis suggests that a loss of function mutation in these genes disrupts ribosome biosynthesis in constituent neural crest cells and neuroepithelium leading to apoptosis. However, recent data illustrating that P53 heterozygosity is protective against TCS, and that P53 and TCOF1 hemizygous embryos do not affect ribosomal function, implicates P53 or elements downstream of P53 as playing a role in TCS pathogenesis. Our study codified nascent findings of the molecular determinants of TCS. These findings add to a burgeoning database of TCS-associated mutations, and as such, can be used to establish TCS diagnosis and further clarify TCS pathogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Cornelia de Lange syndrome: Congenital heart disease in 149 patients.

    Science.gov (United States)

    Ayerza Casas, Ariadna; Puisac Uriol, Beatriz; Teresa Rodrigo, María Esperanza; Hernández Marcos, María; Ramos Fuentes, Feliciano J; Pie Juste, Juan

    2017-10-11

    Cornelia de Lange syndrome (CdLS) is produced by mutations in genes that encode regulatory or structural proteins of the cohesin complex. Congenital heart disease (CHD) is not a major criterion of the disease, but it affects many individuals. The objective of this study was to study the incidence and type of CHD in patients with CdLS. Cardiological findings were evaluated in 149 patients with CdLS and their possible relationship with clinical and genetic variables. A percentage of 34.9 had CHD (septal defects 50%, pulmonary stenosis 27%, aortic coarctation 9.6%). The presence of CHD was related with neonatal hospitalisation (P=.04), hearing loss (P=.002), mortality (P=.09) and lower hyperactivity (P=.02), it being more frequent in HDAC8+ patients (60%), followed by NIPBL+ (33%) and SMC1A+ (28.5%). While septal defects predominate in NIPBL+, pulmonary stenosis is more common in HDAC8+. Patients with CdLS have a high incidence of CHD, which varies according to the affected gene, the most frequent findings being septal defects and pulmonary stenosis. Perform a cardiologic study in all these patients is suggested. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease.

    Science.gov (United States)

    Piccoli, Giorgina B; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M; Pani, Antonello; Veltri, Andrea

    2015-01-01

    The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients.

  2. Interference, heterogeneity and disease gene mapping

    Energy Technology Data Exchange (ETDEWEB)

    Keats, B. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)

    1996-12-31

    The Human Genome Project has had a major impact on genetic research over the past five years. The number of mapped genes is now over 3,000 compared with approximately 1,600 in 1989 and only about 260 ten years before that. The realization that extensive variation could be detected in anonymous DNA segments greatly enhanced the potential for mapping by linkage analysis. Previously, linkage studies had depended on polymorphisms that could be detected in red blood cell antigens, proteins (revealed by electrophoresis and isoelectric focusing), and cytogenetic heteromorphisms. The identification of thousands of polymorphic DNA markers throughout the human genome has led to the construction of high density genetic linkage maps. These maps provide the data necessary to test hypotheses concerning differences in recombination rates and levels of interference. They are also important for disease gene mapping because the existence of these genes must be inferred from the phenotype. Showing linkage of a disease gene to a DNA marker is the first step towards isolating the disease gene, determining its protein product, and developing effective therapies. However, interpretation of results is not always straightforward. Factors such as etiological heterogeneity and undetected irregular segregation can lead to confusing linkage results and incorrect conclusions about the locations of disease genes. This paper will discuss these phenomena and present examples that illustrate the problems, as well as approaches to dealing with them. 23 refs., 3 figs., 3 tabs.

  3. Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

    Science.gov (United States)

    Tian, Cong; Yu, Heping; Yang, Bin; Han, Fengchan; Zheng, Ye; Bartels, Cynthia F.; Schelling, Deborah; Arnold, James E.; Scacheri, Peter C.; Zheng, Qing Yin

    2012-01-01

    Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome. PMID:22539951

  4. [Impulsive-compulsive syndrome in Parkinson's disease].

    Science.gov (United States)

    Nikitina, A V; Fedorova, N V

    2013-01-01

    Dopaminergic replacement therapy (DRT) is effective in treatment the motor symptoms of Parkinson's disease (PD) but can lead to impulse control disorders (ICD) in some patients. ICD include pathological gambling, hypersexuality, compulsive shopping, binge eating, punding, dopamine dysregulation syndrome (DDS). Authors studied the prevalence of ICD and its impact on the quality of life and daily activities of PD patients and their relatives. Among 246 patients studied, 55 patients (23%) (28 men, mean age 66.5±9.4 years) were diagnosed with ICD. DDS was noted in 36.4%, punding in 36.4%, binge eating in 23.6%, hypersexuality in 14.5%, compulsive shopping in 14.5% and pathological gambling in 1.8%. Of these 55 patients, 10 (18.1%) had symptoms of 2 of the ICDs: 3 (5.45%) had 3 of the ICDs and 2 (3.63%) patients had 5 of the ICDs. Quality of life ranged from 25% to 89%. Treatment approaches including the adjustment of doses of levodopa and dopamine receptor agonists in PD patients with ICD are presented.

  5. The primary vascular dysregulation syndrome: implications for eye diseases

    Science.gov (United States)

    2013-01-01

    Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood–brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide

  6. Othello syndrome in patients with Parkinson's disease.

    Science.gov (United States)

    Georgiev, Dejan; Danieli, Aljosa; Ocepek, Lidija; Novak, Dominika; Zupancic-Kriznar, Nina; Trost, Maja; Pirtosek, Zvezdan

    2010-03-01

    Othello syndrome (OS) is an organic delusional disorder with prevailing jealousy symptoms presumably appearing as side effect of antiparkinsonian therapy. The clinical spectrum of psychiatric symptoms in Parkinson's disease (PD) is very wide, including symptoms of depression and anxiety, hallucinations, delusions, with prevalent paranoid symptoms, agitation, delirium and sleep disorders. At our knowledge, just a few cases of patients with PD and OS were reported till now. three neurologists working in a tertiary referral centre were asked to report cases of pathological jealousy as defined by the DSM IV criteria (Kaplan et al. 1994). The following data were collected retrospectively: sex, age at PD onset, age at OS onset, duration of PD, duration of PD treatment, duration of treatment with dopamine agonists (DAs), treatment of OS, past history of alcoholism, premorbid personality disorder, family history of psychiatric disorders and data about general cognitive condition. Five PD patients (three males) with OS were investigated. The mean age of the patients at the PD onset was 46.80+/-8.87 (SD), the mean age at the OS onset was 56.40+/-8.76 (SD). Before the onset of OS, all of them were taking dopamine agonists. The first patient was treated with pramipexole, apomorphine infusion and levodopa/carbidopa, the second with apomorphine infusion plus levodopa/carbidopa/entacapone, the third with pramipexole, the fourth and fifth with ropinirole. Decrease of dopamine agonist led to clinical improvement in three patients (complete reduction of the symptoms in two, reduction of symptoms in one patients). In two patients, the symptoms remained the same. In three patients atypical neuroleptics had to be added: clozapine in two and quetiapine in one patient. We believe that OS is a more common psychiatric side effect in PD patients on treatment with dopamine agonists than usually believed, particulary in those with early disease onset. It is a very disturbing symptom for

  7. Regenerating Gene Protein as a Novel Autoantigen in the Pathogenesis of Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Takashi Fujimoto

    2015-12-01

    Full Text Available Sjögren’s syndrome, an autoimmune disease characterized by exocrine gland dysfunction leading to dry mouth and dry eye diseases, is typified by lymphoplasmacytic infiltrations and a progressive destruction of the salivary and lacrimal glands. Despite an ever-increasing focus on identifying the underlying etiology of Sjögren’s syndrome, the factors that initiate this autoimmune disease and the mechanisms that cause the subsequent exocrine gland dysfunction remain a mystery. The original explanatory concept for the pathogenesis of Sjögren’s syndrome proposed a specific, self-perpetuating, immune-mediated loss of acinar and ductal cells as the principal cause of salivary gland dysfunction. We highlight the possible involvement of regenerating gene (Reg in the regeneration and destruction of salivary gland acinar and ductal cells in Sjögren’s syndrome. The Reg gene was originally isolated as a gene specifically overexpressed in regenerating pancreatic islets and constitutes a growth factor family (Reg family. We describe how salivary gland dysfunction is initiated and maintained and how it can be regenerated or progressed, mediated by the Reg gene, Reg protein, and anti-REG autoantibodies in Sjögren’s syndrome.

  8. Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange-Nielsen syndrome

    Directory of Open Access Journals (Sweden)

    Azam Amirian

    2018-01-01

    Full Text Available Objective(s: Jervell and Lange–Nielsen syndrome is an autosomal recessive disorder caused by mutations in KCNQ1 or KCNE1 genes. The disease is characterized by sensorineural hearing loss and long QT syndrome. Methods: Here we present a 3.5-year-old female patient, an offspring of consanguineous marriage, who had a history of recurrent syncope and congenital sensorineural deafness. The patient and the family members were screened for mutations in KCNQ1 gene by linkage analysis and DNA sequencing. Results: DNA sequencing showed a c.1532_1534delG (p. A512Pfs*81 mutation in the KCNQ1 gene in homozygous form. The results of short tandem repeat (STR markers showed that the disease in the family is linked to the KCNQ1 gene. The mutation was confirmed in the parents in heterozygous form. Conclusion: This is the first report of this variant in KCNQ1 gene in an Iranian family. The data of this study could be used for early diagnosis of the condition in the family and genetic counseling.

  9. Is Pseudoexfoliation Syndrome a Risk Factor for Cerebro Vascular Disease?

    Science.gov (United States)

    Kan, Emrah; Yılmaz, Ahmet; Demirağ, Mehmet Derya; Çalık, Murat

    2017-01-01

    To determine the relationship between cerebro vascular disease and pseudoexfoliation syndrome. This cross-sectional case control study consisted of 50 patients with ischemic-type cerebro vascular disease and 50 control subjects. All subjects were investigated for diabetes mellitus and hypertension status and underwent a detailed ophthalmic examination. A diagnosis of pseudoexfoliation syndrome was made if characteristic greyish particulate matter was found on the anterior lens capsule after pupillary dilatation by slit-lamp examination. All subjects were compared in terms of pseudoexfoliation syndrome, diabetes mellitus, and hypertension. Pearson Chi Square and Student's t test were used for statistical analysis. Logistic regression analyses of the risk factors between groups were also made. The presence of pseudoexfoliation syndrome was significantly higher in patients with cerebro vascular disease when compared to the control subjects (p = 0.02). The frequency of diabetes mellitus was similar between the two groups. Arterial hypertension was significantly more frequent in the patient group when compared to the control subjects (p cerebro vascular disease. In the present study, we found that pseudoexfoliation syndrome frequency was found to be higher in patients with cerebro vascular disease than in control subjects. A slit-lamp examination of the eye could be an important marker that indicates the risk of cerebro vascular disease. We recommend an evaluation of all subjects with pseudoexfoliation syndrome for the presence of cerebro vascular disease. Longitudinal studies with larger populations are needed to confirm this relationship.

  10. Inflammatory bowel disease and irritable bowel syndrome: similarities and differences.

    Science.gov (United States)

    Barbara, Giovanni; Cremon, Cesare; Stanghellini, Vincenzo

    2014-07-01

    Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are classically viewed as dichotomous conditions. The former is perceived as a typical organic disease, and the latter is regarded as a disorder of gut function driven by mood. Recent research identified some shared contributing factors, which will be discussed here. Mounting evidence shows the importance in both IBD and IBS of genetic, microbiological, epithelial, and immunological factors. In some instances, these factors overlap in the two conditions as shown by: involvement of brain-gut axis dysfunction in IBD, implication of TNFSF gene in Crohn's disease and IBS, evidence of abnormal microbiota and its impact on host functions, identification of low-grade inflammation in subsets of IBS patients, and development of IBS symptoms in patients with IBD in remission. IBD and IBS remain separate conditions although there are some overlapping mechanisms. Both research and clinical management would benefit from considering a functional approach for certain manifestations of IBD and accepting an organic view in subsets of IBS patients.

  11. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Sickle Cell Disease in Central India: A Potentially Severe Syndrome.

    Science.gov (United States)

    Jain, Dipty; Warthe, Vinit; Dayama, Paridhi; Sarate, Dilip; Colah, Roshan; Mehta, Pallavi; Serjeant, Graham

    2016-10-01

    To explore clinical, hematological and molecular features of homozygous sickle cell (SS) disease in central India. Focusing on the pediatric age group attending a clinic at the Akola Government Medical College, Akola, Maharashtra State, India, a cross-sectional assessment of 91 patients with sickle cell disease was performed during one week in March 2015. Of the 91 patients, there were 49 with SS disease, 36 with sickle cell-beta thalassemia, and 6 with sickle cell-HbD Punjab. Alpha globin gene deletions occurred in only 8/49 (16 %) SS disease but fetal hemoglobin (HbF) levels were markedly elevated with mean and median of 24.4 %; all except 3 SS disease patients had the Xmn1(+/+) polymorphism consistent with the Asian haplotype. Among the 36 patients with sickle cell-beta thalassemia, 25 (69 %) had the severe beta(+) mutation, IVS1-5 G > C, and seven other molecular mutations, all beta(o) occurred in the other 11 patients. Many patients had a relatively severe clinical course. Comparison of SS disease and sickle cell-beta thalassemia showed no differences in the prevalence of dactylitis, bone pain crisis, acute chest syndrome, hemoglobin level, reticulocyte counts or hydroxyurea usage but patients with sickle cell-beta thalassemia had significantly more blood transfusions, and greater frequencies of splenomegaly and hepatomegaly. Many patients in central India have relatively severe manifestations. This may result from lower frequencies of alpha thalassemia and more frequent severe sickle cell-beta(+) thalassemia. There is a need for assessment of the indications and policies for blood transfusion and for hydroxyurea.

  13. Variant of Rett syndrome and CDKL5 gene

    DEFF Research Database (Denmark)

    Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt

    2012-01-01

    UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have...... been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all...

  14. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2.

    Directory of Open Access Journals (Sweden)

    Catherine Dodé

    2006-10-01

    Full Text Available Kallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mutations in these genes, however, only account for approximately 20% of all Kallmann syndrome cases. In a cohort of 192 patients we took a candidate gene strategy and identified ten and four different point mutations in the genes encoding the G protein-coupled prokineticin receptor-2 (PROKR2 and one of its ligands, prokineticin-2 (PROK2, respectively. The mutations in PROK2 were detected in the heterozygous state, whereas PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state. In addition, one of the patients heterozygous for a PROKR2 mutation was also carrying a missense mutation in KAL1, thus indicating a possible digenic inheritance of the disease in this individual. These findings reveal that insufficient prokineticin-signaling through PROKR2 leads to abnormal development of the olfactory system and reproductive axis in man. They also shed new light on the complex genetic transmission of Kallmann syndrome.

  15. BRUGADA SYNDROME: FROM PRIMARY ELECTRIC HEART DISEASE TO MORPHOLOGICAL SUBSTRATE

    Directory of Open Access Journals (Sweden)

    T. A. Pavlenko

    2016-01-01

    Full Text Available Nowadays interest in channelopathies is growing, and developing diagnostic capabilities make Brugada syndrome much more actual problem than ever. Conception of «primary electric heart disease», which earlier was so popular, now couldn’t explain the absence of single genetic syndromes’ substrate, its’ common combinations with another arrhythmias and the presence of Brugada phenocopy. Conjunction of Brugada syndrome with morphological changes in myocardium , especially myocarditis, is an area of special interest. Infl ammation associates with clinical manifestation of the syndrome, and this situation forces to think about channelopathies’ primacy and to look for another possible mechanisms of Brugada syndrome.

  16. Gene screening in a Chinese family with Marfan syndrome

    Directory of Open Access Journals (Sweden)

    Wen-Jiao Xia

    2016-05-01

    Full Text Available AIM:To analyze the causative gene mutation for Marfan syndrome(MFSwith autosomal dominant hereditary in a Chinese family in Liaoning Province,China. METHODS: Venous blood was collected and candidate gene was selected to design primers according to the clinical phenotype. With genomic polymerase chain reaction(PCRperformed, the coding exons and their flanking intron in sequences of candidate gene were sequenced,DNA fragments separated by agarose gel electrophoresis and direct sequencing method was used to determine the pathogenic gene.RESULTS:Phenotype of the proband was presented as ectopic lentis. Sequencing of the coding regions of FBN1 gene showed the presence of a heterozygous A→G transversion at nucleotide 640 in the 7 exon of FBN1 and the missense mutation made for Glycine into Serine(G214S. CONCLUSION:A heterozygous mutation of FBN1 c.A640G(p.G214Sis responsible for the Marfan syndrome in the four generation Chinese pedigree.

  17. High frequency of celiac disease in Down syndrome

    NARCIS (Netherlands)

    George, EK; Mearin, ML; Bouquet, J; vonBlomberg, ME; Stapel, SO; vanElburg, RM; deGraaf, EAB

    We screened 115 children with Down syndrome for celiac disease, using antigliadin, antiendomysium, and antireticulin serum antibodies and an intestinal permeability test, Celiac disease was diagnosed in eight children, giving a frequency of 7.0%. We recommend screening for celiac disease in all

  18. High frequency of celiac disease in Down syndrome

    NARCIS (Netherlands)

    George, E. K.; Mearin, M. L.; Bouquet, J.; von Blomberg, B. M.; Stapel, S. O.; van Elburg, R. M.; de Graaf, E. A.

    1996-01-01

    We screened 115 children with Down syndrome for celiac disease, using antigliadin, antiendomysium, and antireticulin serum antibodies and an intestinal permeability test, Celiac disease was diagnosed in eight children, giving a frequency of 7.0%. We recommend screening for celiac disease in all

  19. EULAR Sjögren's syndrome disease activity index (ESSDAI)

    DEFF Research Database (Denmark)

    Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar

    2015-01-01

    The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now i...

  20. Searching for new pharmacological targets for the treatment of Alzheimer's disease in Down syndrome.

    Science.gov (United States)

    Caraci, Filippo; Iulita, M Florencia; Pentz, Rowan; Flores Aguilar, Lisi; Orciani, Chiara; Barone, Concetta; Romano, Corrado; Drago, Filippo; Cuello, A Claudio

    2017-12-15

    Individuals with Down syndrome are at increased risk of developing Alzheimer's disease due to increase gene dosage resulting from chromosome 21 triplication. Although virtually all adults with Down syndrome will exhibit the major neuropathological hallmarks that define Alzheimer's disease, not all of them will develop the clinical symptoms associated with this disorder (i.e. dementia). Therefore, a good understanding of the pathophysiology of Alzheimer's disease in Down syndrome will be crucial for the identification of novel pharmacological targets to develop disease-modifying therapies for the benefit of Down syndrome individuals and for Alzheimer's sufferers alike. The study of biomarkers will also be essential for the development of better screening tools to identify dementia at its incipient stages. This review discusses the best-validated pharmacological targets for the treatment of cognitive impairment and Alzheimer's disease in Down syndrome. We further examine the relevance of newly discovered biological markers for earlier dementia diagnosis in this population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  1. Histiocytoid Sweet Syndrome in a Child without Underlying Systemic Disease.

    Science.gov (United States)

    Yeom, Seung Dohn; Ko, Hye Soo; Moon, Jong Hyuk; Kang, Min Ji; Byun, Ji Won; Choi, Gwang Seong; Shin, Jeonghyun

    2017-10-01

    Sweet syndrome (acute, febrile, neutrophilic dermatosis) is characterized by the acute onset of an eruption of painful nodules or erythematous or violaceous plaques on the limbs, face and neck. These symptoms are accompanied by fever. The diagnostic features include histopathological findings of dermal neutrophilic infiltration without leukocytoclastic vasculitis or peripheral blood leukocytosis. Sweet syndrome is associated with infection, malignancies, autoimmune disease, pregnancy, and drugs. Patients with Sweet syndrome demonstrate a complete and rapid response to systemic steroid administration. Recently, a distinct variant of Sweet syndrome was reported, termed "histiocytoid Sweet syndrome", in which the infiltration of myeloperoxidase-positive histiocytoid mononuclear cells are observed (in contrast to the infiltration of neutrophils). The other clinical features are similar to those of classic Sweet syndrome. Pediatric Sweet syndrome is uncommon, and the histiocytoid type is even rarer. To date, four cases of histiocytoid Sweet syndrome have been reported in children. Herein, we describe a case of histiocytoid Sweet syndrome in an otherwise healthy 10-year-old boy with no underlying systemic disease in whom non-steroidal, anti-inflammatory drug treatment was successful.

  2. Identification of the gene for Nance-Horan syndrome (NHS)

    OpenAIRE

    Brooks, S. P.; Ebenezer, N. D.; Poopalasundaram, S.; Lehmann, O. J.; Moore, A. T.; Hardcastle, A. J.

    2004-01-01

    Objective: To identify the gene or genes responsible for these diseases. Methods: Families with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA....

  3. Clinical Syndromes Associated with Cardiovascular Diseases: A Review

    Directory of Open Access Journals (Sweden)

    Xing Sheng Yang, MD, PhD, FACC, FAHA

    2017-02-01

    Full Text Available In clinical practice, a variety of syndromes are associated with cardiovascular disease and have characteristic findings. Most of them are an autosomal dominant genetic disorder and have different types of cardiovascular abnormalities, including electrocardiographic conduction defects, arrhythmias, cardiomyopathy, vascular and valvular diseases, cardiac septal defects, and pulmonary problems. There is a growing need for physicians to pay more attention to these syndromes.

  4. Mutations du gene de la filamine et syndromes malformatifs | Koffi ...

    African Journals Online (AJOL)

    Filamin is a cytoskeletal protein that occurs in the control of cytoskeleton structure and activity, the modulation of cell shape and migration as well as in the maintaining of cell shape. Mutations in the genes FLNA and FLNB provoke diverse malformative diseases in human. Mutations in the gene FLNA cause four X-Linked ...

  5. Metabolic Syndrome and Chronic Renal Disease

    Directory of Open Access Journals (Sweden)

    Vaia D. Raikou

    2018-01-01

    Full Text Available Background: The influence of metabolic syndrome (MetS on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR and/or the presence of microalbuminuria/macroalbuminuria. Methods: 149 patients (77 males/72 females were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x2 = 50.3, p = 0.001 and x2 = 26.9, p = 0.003 respectively was found to be significant. The MetS presence showed an odds 5.3-fold (1.6–17.8 higher for low eGFR and 3.2-fold (1.2–8.8 higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1–11.3. Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x2 = 11.8, p = 0.003, x2 = 11.4, p = 0.003 and x2 = 9.1, p = 0.01 respectively, and it was mildly associated with a low HDL-C (x2 = 5.7, p = 0.06. A significant association between classified eGFR and both high triglycerides and hypertension (x2 = 9.7, p = 0.04 and x2 = 16.1, p = 0.003 respectively was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.

  6. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Hansen, Torben; Lajer, Maria

    2004-01-01

    a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate...

  7. Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

    Directory of Open Access Journals (Sweden)

    Marcelo Cury

    2013-01-01

    Full Text Available There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS, Ehlers-Danlos syndrome (EDS, Loeys-Dietz syndrome (LDS, familial thoracic aortic aneurysms and dissections (TAAD, bicuspid aortic valve disease (BAV, and autosomal dominant polycystic kidney disease (ADPKD. In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

  8. The rationale and design of Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT): a prospective cohort study of childhood nephrotic syndrome.

    Science.gov (United States)

    Hussain, Neesha; Zello, J Anastasia; Vasilevska-Ristovska, Jovanka; Banh, Tonny M; Patel, Viral P; Patel, Pranali; Battiston, Christopher D; Hebert, Diane; Licht, Christoph P B; Piscione, Tino D; Parekh, Rulan S

    2013-01-26

    Nephrotic syndrome is one of the most commonly diagnosed kidney diseases in childhood and its progressive forms can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). There have been few longitudinal studies among a multi-ethnic cohort to determine potential risk factors influencing disease susceptibility, treatment response, and progression of nephrotic syndrome. Temporal relationships cannot be studied through cross-sectional study design. Understanding the interaction between various factors is critical to developing new strategies for treating children with kidney disease. We present the rationale and the study design of a longitudinal cohort study of children with nephrotic syndrome, the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) study. The specific aims are to determine: 1) socio-demographic, environmental, and genetic factors that influence disease susceptibility; 2) rates of steroid treatment resistance and steroid treatment dependence, and identify factors that may modify treatment response; 3) clinical and genetic factors that influence disease susceptibility and progression to CKD and ESRD; and 4) the interaction between the course of illness and socio-demographic, environmental, and clinical risk factors. INSIGHT is a disease-based observational longitudinal cohort study of children with nephrotic syndrome. At baseline, participants complete questionnaires and provide biological specimen samples (blood, urine, and toenail clippings). Follow-up questionnaires and repeat biological specimen collections are performed annually for up to five years. The proposed cohort will provide the structure to test various risk factors predicting or influencing disease susceptibility, treatment response, and progression to CKD among children with nephrotic syndrome. ClinicalTrials.gov Identifier NCT01605266.

  9. Mutation spectrum of genes associated with steroid-resistant nephrotic syndrome in Chinese children.

    Science.gov (United States)

    Wang, Ying; Dang, Xiqiang; He, Qingnan; Zhen, Yan; He, Xiaoxie; Yi, Zhuwen; Zhu, Kuichun

    2017-08-20

    Approximately 20% of children with idiopathic nephrotic syndrome do not respond to steroid therapy. More than 30 genes have been identified as disease-causing genes for the steroid-resistant nephrotic syndrome (SRNS). Few reports were from the Chinese population. The coding regions of genes commonly associated with SRNS were analyzed to characterize the gene mutation spectrum in children with SRNS in central China. The first phase study involved 38 children with five genes (NPHS1, NPHS2, PLCE1, WT1, and TRPC6) by Sanger sequencing. The second phase study involved 33 children with 17 genes by next generation DNA sequencing (NGS. 22 new patients, and 11 patients from first phase study but without positive findings). Overall deleterious or putatively deleterious gene variants were identified in 19 patients (31.7%), including four NPHS1 variants among five patients and three PLCE1 variants among four other patients. Variants in COL4A3, COL4A4, or COL4A5 were found in six patients. Eight novel variants were identified, including two in NPHS1, two in PLCE1, one in NPHS2, LAMB2, COL4A3, and COL4A4, respectively. 55.6% of the children with variants failed to respond to immunosuppressive agent therapy, while the resistance rate in children without variants was 44.4%. Our results show that screening for deleterious variants in some common genes in children clinically suspected with SRNS might be helpful for disease diagnosis as well as prediction of treatment efficacy and prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Metabolic syndrome and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Anis Belarbia

    2015-01-01

    Full Text Available To determine the prevalence of metabolic syndrome (MS in chronic kidney disease (CKD patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul′s University Hospital of Sousse (Tunisia over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6% was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR was 55.8 ± 49.2 mL/min. Cardiovascular (CV impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI. CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

  11. Metabolic syndrome and chronic kidney disease.

    Science.gov (United States)

    Belarbia, Anis; Nouira, Safa; Sahtout, Wissal; Guedri, Yosra; Achour, Abdellatif

    2015-09-01

    To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 ± 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

  12. Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.

    Science.gov (United States)

    Yang, Hang; Luo, Mingyao; Chen, Qianlong; Fu, Yuanyuan; Zhang, Jing; Qian, Xiangyang; Sun, Xiaogang; Fan, Yuxin; Zhou, Zhou; Chang, Qian

    2016-08-01

    Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder typically involving the ocular, skeletal and cardiovascular systems, and aortic aneurysms/dissection mainly contributes to its mortality. Here, we performed genetic testing of the FBN1 gene in 39 Chinese probands with Marfan/Marfan-like syndrome and their related family members by Sanger sequencing. In total, 29 pathogenic/likely pathogenic FBN1 mutations, including 17 novel ones, were identified. In addition, most MFS patients with aortic disease (62%) had a truncating or splicing mutation. These results expand the FBN1 mutation spectrum and enrich our knowledge of genotype-phenotype correlations. Genetic testing for MFS and its related aortic diseases is increasingly important for early intervention and treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. RAI1 gene mutations: mechanisms of Smith-Magenis syndrome.

    Science.gov (United States)

    Falco, Mariateresa; Amabile, Sonia; Acquaviva, Fabio

    2017-01-01

    Smith-Magenis syndrome (SMS; OMIM #182290) is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions, encompassing multiple genes and including the retinoic acid-induced 1 gene ( RAI1 ), or by mutations in RAI1 itself. About 10% of all the SMS patients, in fact, carry an RAI1 mutation responsible for the phenotype. RAI1 (OMIM *607642) is a dosage-sensitive gene expressed in many tissues and highly conserved among species. Over the years, several studies have demonstrated that RAI1 (or its homologs in animal models) acts as a transcriptional factor implicated in embryonic neurodevelopment, neuronal differentiation, cell growth and cell cycle regulation, bone and skeletal development, lipid and glucose metabolisms, behavioral functions, and circadian activity. Patients with RAI1 pathogenic variants show some phenotypic differences when compared to those carrying the typical deletion. They usually have lower incidence of hypotonia and less cognitive impairment than those with 17p11.2 deletions but more frequently show the behavioral characteristics of the syndrome and overeating issues. These differences reflect the primary pathogenetic role of RAI1 without the pathogenetic contribution of the other genes included in the typical 17p11.2 deletion. The better comprehension of physiological roles of RAI1 , its molecular co-workers and interactors, and its contribution in determining the typical SMS phenotype will certainly open a new path for therapeutic interventions.

  14. Congenital diseases and syndromes. An illustrated radiological guide

    International Nuclear Information System (INIS)

    Al-Tubaikh, Jarrah Ali; Sabah Hospital; Reiser, Maximilian F.

    2009-01-01

    Congenital Diseases and Syndromes - An Illustrated Radiological Guide is designed to serve the radiologist as an easy-to-use visual guide that illustrates the typical diagnostic radiological features of the most common congenital diseases and syndromes. The book is organised according to body system, with chapters focusing on the CNS, the head and neck, the chest and heart, the abdomen and pelvis, and the musculoskeletal system. A final chapter is devoted to phakomatosis. Each syndrome or disease is illustrated by multiple images as well as by high-quality digital medical illustrations depicting those radiological signs that are difficult to detect. The reader is thereby familiarised with the various congenital anomalies from the radiological point of view. In addition, etiology, diagnostic criteria, and main symptoms are described, and potential differential diagnoses highlighted. This book will be immensely useful for junior radiologists, radiology students, and doctors in any specialty who are interested in congenital malformations and syndromes. (orig.)

  15. Síndrome de Diógenes Diogenes syndrome

    Directory of Open Access Journals (Sweden)

    Bárbara Perdigão Stumpf

    2010-01-01

    Full Text Available A síndrome de Diógenes (SD caracteriza-se por descuido extremo com a higiene pessoal, negligência com o asseio da própria moradia, isolamento social, suspeição e comportamento paranoico, sendo frequente a ocorrência de colecionismo. A incidência anual é de 5/10.000 entre aqueles acima de 60 anos, e pelo menos a metade é portadora de demência ou algum outro transtorno psiquiátrico. As principais hipóteses etiológicas são: (1 a condição representaria o "estágio final" de um transtorno de personalidade; (2 a síndrome seria uma manifestação de demência do lobo frontal; (3 a SD seria o estágio final do subtipo hoarding do TOC; (4 a SD seria uma via final comum a diferentes transtornos psiquiátricos, especialmente aqueles associados ao colecionismo; (5 a síndrome seria precipitada por estressores biológicos, psicológicos e sociais, associados com a idade, em indivíduos com traços de personalidade predisponentes. É conhecido que existem apenas relatos de casos envolvendo tratamentos específicos para a SD, particularmente a risperidona. Por se tratar de condição grave, com elevada mortalidade por problemas clínicos, estudos se fazem necessários para determinar as melhores estratégias de abordagem desses pacientes. Os autores descrevem o caso de uma paciente com SD e fazem uma breve revisão da literatura.Diogenes syndrome (DSis characterized by extreme self-neglect, domestic squalor, social withdrawal, suspiciousness and paranoid behaviour and is often accompanied by excessive hoarding. The annual incidence is five per ten thousand of the population aged over 60, at least half of whom will have dementia or some other form of mental illness. The main etiological hypotheses are: (1 the condition represents the "end-stage" of a personality disorder; (2 the syndrome is a manifestation of a frontal-lobe dementia; (3 DS may be an end stage of the hoarding subtype of OCD; (4 DS may be a final common pathway of different

  16. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

    Science.gov (United States)

    Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

    2010-03-01

    Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

  17. c.376G>A mutation in WFS1 gene causes Wolfram syndrome without deafness.

    Science.gov (United States)

    Safarpour Lima, Behnam; Ghaedi, Hamid; Daftarian, Narsis; Ahmadieh, Hamid; Jamshidi, Javad; Khorrami, Mehdi; Noroozi, Rezvan; Sohrabifar, Nasim; Assarzadegan, Farhad; Hesami, Omid; Taghavi, Shaghayegh; Ahmadifard, Azadeh; Atakhorrami, Minoo; Rahimi-Aliabadi, Simin; Shahmohammadibeni, Neda; Alehabib, Elham; Andarva, Monavvar; Darvish, Hossein; Emamalizadeh, Babak

    2016-02-01

    Wolfram syndrome is one of the rare autosomal recessive, progressive, neurodegenerative disorders, characterized by diabetes mellitus and optic atrophy. Several other features are observed in patients including deafness, ataxia, and peripheral neuropathy. A gene called WFS1 is identified on chromosome 4p, responsible for Wolfram syndrome. We investigated a family consisted of parents and 8 children, which 5 of them have been diagnosed for Wolfram syndrome. WFS1 gene in all family members was sequenced for causative mutations. A mutation (c.376G>A, p.A126T) was found in all affected members in homozygous state and in both parents in heterozygous state. The bioinformatics analysis showed the deleterious effects of this nucleotide change on the structure and function of the protein product. As all of the patients in the family showed the homozygote mutation, and parents were both heterozygote, this mutation is probably the cause of the disease. We identified this mutation in homozygous state for the first time as Wolfram syndrome causation. We also showed that this mutation probably doesn't cause deafness in affected individuals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. RAI1 gene mutations: mechanisms of Smith–Magenis Syndrome

    Directory of Open Access Journals (Sweden)

    Falco M

    2017-11-01

    Full Text Available Mariateresa Falco,1,* Sonia Amabile,1,* Fabio Acquaviva2 1Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy; 2Department of Translational Medical Sciences (DISMET, Section of Pediatric Clinical Genetics, University of Naples “Federico II”, Naples, Italy *These authors contributed equally to this work Abstract: Smith–Magenis syndrome (SMS; OMIM #182290 is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions, encompassing multiple genes and including the retinoic acid-induced 1 gene (RAI1, or by mutations in RAI1 itself. About 10% of all the SMS patients, in fact, carry an RAI1 mutation responsible for the phenotype. RAI1 (OMIM *607642 is a dosage-sensitive gene expressed in many tissues and highly conserved among species. Over the years, several studies have demonstrated that RAI1 (or its homologs in animal models acts as a transcriptional factor implicated in embryonic neurodevelopment, neuronal differentiation, cell growth and cell cycle regulation, bone and skeletal development, lipid and glucose metabolisms, behavioral functions, and circadian activity. Patients with RAI1 pathogenic variants show some phenotypic differences when compared to those carrying the typical deletion. They usually have lower incidence of hypotonia and less cognitive impairment than those with 17p11.2 deletions but more frequently show the behavioral characteristics of the syndrome and overeating issues. These differences reflect the primary pathogenetic role of RAI1 without the pathogenetic contribution of the other genes included in the typical 17p11.2 deletion. The better comprehension of physiological roles of RAI1, its molecular co-workers and interactors, and its contribution in determining the typical SMS phenotype will certainly open a new path

  19. Linking Genes to Cardiovascular Diseases: Gene Action and Gene–Environment Interactions

    Science.gov (United States)

    2016-01-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the “post-genomic” era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how “modifier genes” influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many—practitioners and investigators—to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area. PMID:26545598

  20. [Study of gene mutation and pathogenetic mechanism for a family with Waardenburg syndrome].

    Science.gov (United States)

    Chen, Hongsheng; Liao, Xinbin; Liu, Yalan; He, Chufeng; Zhang, Hua; Jiang, Lu; Feng, Yong; Mei, Lingyun

    2017-08-10

    To explore the pathogenetic mechanism of a family affected with Waardenburg syndrome. Clinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively. A heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITF wild and mutant MITF R255X were confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm. The c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.

  1. Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

    Directory of Open Access Journals (Sweden)

    Tai Dessmon

    2005-01-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs derived from SARS patients, and compared with healthy controls. Results The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis. Conclusions This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.

  2. Periodic fever: From Still's disease to Muckle-Wells syndrome.

    Science.gov (United States)

    Solís Marquínez, Marta Nataya; García Fernández, Edilia; Morís de la Tassa, Joaquín

    2017-06-02

    Muckle-Wells syndrome is a systemic autoinflammatory disease included in the group of hereditary periodic febrile syndromes. We report the case of a patient with this rare disease to call the attention to the singularity of this condition, its low incidence, its atypical presentation and the subsequent delay in the diagnosis, which is reached when late and devastating consequences have taken place. In this case, the first-line therapy, anti-interleukin 1 (IL-1), failed to control the disease. Nevertheless, the IL-6 inhibitor, tocilizumab, proved effective, achieving the total remission of nephrotic syndrome associated with AA secondary amyloidosis, changing the bleak prognosis of this disease. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. Does a carpal tunnel syndrome predict an underlying disease?

    NARCIS (Netherlands)

    M.C. de Rijk (Maarten); F.H. Vermeij (Frederique); M. Suntjens (Maartje); P.A. van Doorn (Pieter)

    2007-01-01

    textabstractCarpal tunnel syndrome (CTS) may be the presenting symptom of an underlying disease such as diabetes mellitus, hypothyroidism or connective tissue disease (CTD). It was investigated whether additional blood tests (glucose level, thyroid-stimulating hormone level and erythrocyte

  4. Development of disease-specific growth charts in Turner syndrome and Noonan syndrome

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Isojima

    2017-12-01

    Full Text Available Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

  5. Development of disease-specific growth charts in Turner syndrome and Noonan syndrome.

    Science.gov (United States)

    Isojima, Tsuyoshi; Yokoya, Susumu

    2017-12-01

    Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

  6. Analysis of ferritin genes in Parkinson disease.

    Science.gov (United States)

    Foglieni, Barbara; Ferrari, Francesca; Goldwurm, Stefano; Santambrogio, Paolo; Castiglioni, Emanuela; Sessa, Maria; Volontè, Maria Antonietta; Lalli, Stefania; Galli, Carlo; Wang, Xin-Sheng; Connor, James; Sironi, Francesca; Canesi, Margherita; Biasiotto, Giorgio; Pezzoli, Gianni; Levi, Sonia; Ferrari, Maurizio; Arosio, Paolo; Cremonesi, Laura

    2007-01-01

    Genes that regulate iron metabolism may be involved in increasing brain iron content in Parkinson disease (PD). The ferritin L-chain is one of these genes, but the rare insertional mutations that cause neuroferritinopathy with basal ganglia degeneration have not yet been identified in PD. We used denaturing HPLC (DHPLC) to investigate 124 PD patients and 180 controls for variations in the coding and in the 5' untranslated regions of the H- and L-ferritin genes. In the H-ferritin gene, we found one new and rather common intronic polymorphism and the K54R substitution in two controls. The L-ferritin gene showed a very common L55L polymorphism and four other types of DNA variations, three of which were in the patient cohort. A mutation of the conserved His133 to Pro was found in a PD patient and in his daughter. The patient did not show signs of neuroferritinopathy, but the mutation was associated with low L-ferritin levels and with mild chronic anemia. The results support the hypothesis that DNA variations in the ferritin genes are not a common cause for PD.

  7. Identifying human disease genes through cross-species gene mapping of evolutionary conserved processes.

    Directory of Open Access Journals (Sweden)

    Martin Poot

    2011-05-01

    Full Text Available Understanding complex networks that modulate development in humans is hampered by genetic and phenotypic heterogeneity within and between populations. Here we present a method that exploits natural variation in highly diverse mouse genetic reference panels in which genetic and environmental factors can be tightly controlled. The aim of our study is to test a cross-species genetic mapping strategy, which compares data of gene mapping in human patients with functional data obtained by QTL mapping in recombinant inbred mouse strains in order to prioritize human disease candidate genes.We exploit evolutionary conservation of developmental phenotypes to discover gene variants that influence brain development in humans. We studied corpus callosum volume in a recombinant inbred mouse panel (C57BL/6J×DBA/2J, BXD strains using high-field strength MRI technology. We aligned mouse mapping results for this neuro-anatomical phenotype with genetic data from patients with abnormal corpus callosum (ACC development.From the 61 syndromes which involve an ACC, 51 human candidate genes have been identified. Through interval mapping, we identified a single significant QTL on mouse chromosome 7 for corpus callosum volume with a QTL peak located between 25.5 and 26.7 Mb. Comparing the genes in this mouse QTL region with those associated with human syndromes (involving ACC and those covered by copy number variations (CNV yielded a single overlap, namely HNRPU in humans and Hnrpul1 in mice. Further analysis of corpus callosum volume in BXD strains revealed that the corpus callosum was significantly larger in BXD mice with a B genotype at the Hnrpul1 locus than in BXD mice with a D genotype at Hnrpul1 (F = 22.48, p<9.87*10(-5.This approach that exploits highly diverse mouse strains provides an efficient and effective translational bridge to study the etiology of human developmental disorders, such as autism and schizophrenia.

  8. Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

    International Nuclear Information System (INIS)

    Storch, A.

    2002-01-01

    Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

  9. Early Disseminated Lyme Disease with Carditis Complicated by Posttreatment Lyme Disease Syndrome

    OpenAIRE

    Novak, Cheryl; Harrison, Andrew; Aucott, John

    2017-01-01

    Lyme disease is an infectious disease caused by the bacterium Borrelia burgdorferi. When untreated, infection may spread to the heart, nervous system, and joints. Cardiac involvement usually manifests as abnormalities of the conduction system and bradycardia. Treatment of Lyme disease is generally effective, with a subset of patients experiencing persistent, sometimes long-term symptoms called posttreatment Lyme disease syndrome.

  10. Gene-Environment Interaction in Parkinson's Disease

    DEFF Research Database (Denmark)

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen

    2016-01-01

    BACKGROUND AND PURPOSE: Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2......) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. METHODS: In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between...... lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. RESULTS: We estimated statistically significant...

  11. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  12. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, P; Limburg, P; Kallenberg, C; Minderaa, R; Battistin, L

    2004-01-01

    Tourette's syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While its pathogenesis at a molecular and cellular level remains unknown, recent research findings point to the possible involvement of autoimmunity in at least a

  13. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Thang S Han

    2016-02-01

    Full Text Available The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30–40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5–10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35–40 kg/m 2 with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists.

  14. Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome.

    Science.gov (United States)

    Forsythe, Elizabeth; Sparks, Kathryn; Best, Sunayna; Borrows, Sarah; Hoskins, Bethan; Sabir, Ataf; Barrett, Timothy; Williams, Denise; Mohammed, Shehla; Goldsmith, David; Milford, David V; Bockenhauer, Detlef; Foggensteiner, Lukas; Beales, Philip L

    2017-03-01

    Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes ( BBS1-19 ) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet-Biedl syndrome-related renal disease attending the United Kingdom national Bardet-Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4-5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10 , mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b-5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet-Biedl syndrome and identifies risk factors to be considered in genetic counseling. Copyright © 2017 by the American Society of Nephrology.

  15. Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian Turner Syndrome patients.

    Science.gov (United States)

    Ismail, Manal F; Zarouk, Waheba A; Ruby, Mona O; Mahmoud, Wael M; Gad, Randa S

    2015-01-01

    Folate metabolism dysfunctions can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) encoding gene (C677T and A1298C) reduce MTHFR activity, but when associated with aneuploidy, the results are conflicting. Turner Syndrome (TS) is an interesting model for investigating the association between MTHFR gene polymorphisms and nondisjunction because of the high frequency of chromosomal mosaicism in this syndrome. To investigate the association of MTHFR gene C677T and A1298C polymorphisms in TS patients and their mothers and to correlate these polymorphisms with maternal risk of TS offspring. MTHFR C677T and A1298C polymorphisms were genotyped in 33 TS patients, their mothers and 15 healthy females with their mothers as controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing technique. Genotype and allele frequencies of both C677T and A1298C were not significantly different between TS cases and controls. There were no significant differences in C677T genotype distribution between the TS mothers and controls (p=1). The MTHFR 1298AA and 1298AC genotypes were significantly increased in TS mothers Vs. control mothers (p=0.002). The C allele frequency of the A1298C polymorphism was significantly different between the TS mothers and controls (p=0.02). The association of A1298C gene polymorphism in TS patients was found to increase with increasing age of both mothers (p=0.026) and fathers (p=0.044) of TS cases. Our findings suggest a strong association between maternal MTHFR A1298C and risk of TS in Egypt.

  16. Paraoxnase1 Gene Polymorphism in Childhood Idiopathic Nephrotic Syndrome.

    Science.gov (United States)

    Al-Eisa, Amal A; Sukumaran, Vazhappilly J; Haider, Mohammad Z

    2016-01-01

    Paraoxonase1 (PON1) is a serum enzyme bound to high-density lipoproteins with antioxidant properties. Molecular studies of PON1 revealed 2 polymorphic sites at amino acids 55 and 192 resulting in 2 different allozymes, the L and M-genotype at residue 55 and A and B at site 192, respectively. We have studied the association between PON1 gene polymorphisms and the minimal change nephrotic syndrome/focal segmental glomerulosclerosis (MCNS/FSGS) types of idiopathic nephrotic syndrome (INS) in Kuwaiti Arab children. The PON1 gene, 55 and 192 polymorphisms were analyzed in 50 children with INS (32 MSCN, 18 FSGS) and compared to 50 controls. Serum creatinine, albumin and lipids were measured in all subjects. The LL genotype was detected in 50% of the INS patients compared to 48% of controls (p = 0.84). The heterozygous LM genotype was detected in 42% of INS patients compared 36% of controls (p = 0.68). The MM-genotype was detected in 8% of INS patients and 16% of controls (p = 0.35). The L-allele frequency in its homozygous and heterozygous forms was found in 71% of INS patients compared to 66% controls (p = 0.54). The L-allele frequency (LM and LL) was significantly higher in FSGS compared to MCNS patients (p = 0.0001) and when compared to controls (p = 0.0007). All patients and controls had the AA form of the 192 PON1 gene polymorphism. Our data demonstrate a strong association between the L-allele of PON1 gene 55 polymorphism with FSGS in Kuwaiti Arab children with INS. PON1 genotyping can help in the early prediction of FSGS, which might guide clinicians to a better therapeutic approach. © 2016 S. Karger AG, Basel.

  17. Novel LRP5 gene mutation in a patient with osteoporosis-pseudoglioma syndrome.

    Science.gov (United States)

    Marques-Pinheiro, Alice; Levasseur, Régis; Cormier, Catherine; Bonneau, Jessica; Boileau, Catherine; Varret, Mathilde; Abifadel, Marianne; Allanore, Yannick

    2010-03-01

    Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder characterised by severe juvenile-onset osteoporosis and congenital or early-onset blindness. This serious illness is due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) that is a major actor in pathways involved in bone remodelling. Here, we report a novel frameshift mutation identified in a 22 year-old Tunisian boy of a consanguineous family. This patient had low bone mineral density (BMD), experienced multiple fractures during childhood and suffered ocular alterations with blindness. Direct DNA sequencing showed a homozygous 5 base pair insertion in exon 5 of the LRP5 gene. This new mutation is located in the first EGF-like domain and gives rise to a truncated protein of 384 amino acids. The functional significance of this mutation clearly indicates a loss-of-function mutation of the LRP5 gene leading to the observed OPPG phenotype. Rheumatologists must be aware of LRP5 gene that in addition to being a major gene in the mendelian disease that is OPPG syndrome seems to be involved in osteoporosis in the general population through some of its polymorphisms. Copyright 2009 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  18. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

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    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S. (National Cancer Institute, Frederick, MD (USA))

    1988-10-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.

  19. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

    International Nuclear Information System (INIS)

    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S.

    1988-01-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease

  20. Unraveling the Pathophysiology of Sjogren Syndrome-Associated Dry Eye Disease

    Science.gov (United States)

    Nguyen, Cuong Q.; Peck, Ammon B.

    2010-01-01

    Sjogren syndrome (SS) is one of the most common autoimmune diseases. Early clinical manifestations of SS are primarily decreased tear and saliva secretion, leading to dry eye and dry mouth syndromes, but in its later stages, it can become systemic, even resulting in B cell lymphomas. The use of new animal models, coupled with new technologies, is providing exciting insights into the pathogenesis, genetic predisposition, and, possibly, early diagnosis of SS. This article reviews newly described features of SS identified in experimental animal models and their relationship to human disease. New technologies, such as genomics and proteomics, may permit identification of potential candidate genes and biomarkers for disease diagnosis. Current studies using appropriate animal models in parallel with studies of human subjects is rapidly establishing a foundation for new intervention strategies that go beyond merely treating symptoms. PMID:19214349

  1. Defining the Role of Essential Genes in Human Disease

    Science.gov (United States)

    Robertson, David L.; Hentges, Kathryn E.

    2011-01-01

    A greater understanding of the causes of human disease can come from identifying characteristics that are specific to disease genes. However, a full understanding of the contribution of essential genes to human disease is lacking, due to the premise that these genes tend to cause developmental abnormalities rather than adult disease. We tested the hypothesis that human orthologs of mouse essential genes are associated with a variety of human diseases, rather than only those related to miscarriage and birth defects. We segregated human disease genes according to whether the knockout phenotype of their mouse ortholog was lethal or viable, defining those with orthologs producing lethal knockouts as essential disease genes. We show that the human orthologs of mouse essential genes are associated with a wide spectrum of diseases affecting diverse physiological systems. Notably, human disease genes with essential mouse orthologs are over-represented among disease genes associated with cancer, suggesting links between adult cellular abnormalities and developmental functions. The proteins encoded by essential genes are highly connected in protein-protein interaction networks, which we find correlates with an over-representation of nuclear proteins amongst essential disease genes. Disease genes associated with essential orthologs also are more likely than those with non-essential orthologs to contribute to disease through an autosomal dominant inheritance pattern, suggesting that these diseases may actually result from semi-dominant mutant alleles. Overall, we have described attributes found in disease genes according to the essentiality status of their mouse orthologs. These findings demonstrate that disease genes do occupy highly connected positions in protein-protein interaction networks, and that due to the complexity of disease-associated alleles, essential genes cannot be ignored as candidates for causing diverse human diseases. PMID:22096564

  2. The metabolic syndrome and vascular disease

    NARCIS (Netherlands)

    Olijhoek, Jobien Karen

    2006-01-01

    In the Western population cardiovascular diseases are the most common cause of mortality and morbidity. There are several important risk factors for cardiovascular diseases, among them hypertension, hypercholesterolemia, diabetes and obesity. The clustering of cardiovascular risk factors associated

  3. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    Directory of Open Access Journals (Sweden)

    S. Marrakchi

    2014-01-01

    Full Text Available Background. It is important to recognise Wolff-Parkinson-White (WPW syndrome in electrocardiograms (ECG, as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

  4. Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.

    Science.gov (United States)

    Lindwall, Elvira; Singla, Shikha; Davis, William E; Quinet, Robert J

    2015-08-01

    Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant disease that usually presents in childhood with recurrent sterile arthritis. As the child ages into puberty, cutaneous features develop and arthritis subsides. We report the case of a now 25-year-old male patient with PAPA syndrome with the E250K mutation in PSTPIP1. We also present a systematic literature review of other PAPA cases. We conducted a literature search of PubMed using the following search terms: E250K mutation, PSTPIP1, and PAPA. PAPA syndrome is caused by mutations on chromosome 15q affecting the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene, also known as CD2-binding protein 1 (CD2BP1). The reported cases of PAPA syndrome currently in the literature involve mutations in A230T and E250Q. One case of a novel E250K mutation has been reported, which presented with a different phenotype to previously described cases of PAPA syndrome. With variation present between disease presentations from case to case, it is possible that the spectrum of PAPA syndrome is wider than currently thought. Further research is needed which may uncover an as-yet undiscovered genetic abnormality linking these interrelated diseases together. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Biomedical Information Extraction: Mining Disease Associated Genes from Literature

    Science.gov (United States)

    Huang, Zhong

    2014-01-01

    Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

  6. Willis-Ekbom Disease or Restless Legs Syndrome?

    Science.gov (United States)

    Carlos, K; Prado, L B F; Carvalho, L B C; Prado, G F

    2015-09-01

    Restless Legs Syndrome (RLS) or Willis-Ekbom Disease (WED) is highly prevalent, but patients and healthcare providers alike know little about it. Furthermore, controversy persists as to the best way of diagnosing this nosological entity. To verify whether the term used to refer to this disease entity (Restless Legs Syndrome or Willis-Ekbom Disease) affects the prevalence of self-diagnosed RLS/WED in a sample of newly graduated physicians. Newly graduated physicians were asked to self-evaluate for the presence of RLS/WED. Briefly, participants were allocated randomly across two groups. One was asked to self-assess for RLS, while the other was asked to self-assess for WED. The evaluation form given to one group asked 'Do you have Restless Legs Syndrome?' whereas the form given to participants in the other group asked 'Do you have Willis-Ekbom Disease?'. Both forms also contained the four criteria for diagnosing RLS proposed by the International Restless Legs Syndrome Study Group (IRLSSG) and instructions for self-diagnosis according to these criteria. The study sample comprised 1413 newly graduated physicians. Of the 708 participants who were given the form that used the term RLS, 87 (12.28%) diagnosed themselves with the condition. Conversely, of 705 physicians given the form with the term WED, 13 (1.84%) diagnosed themselves with the condition (p Restless Legs Syndrome than when presented with the term Willis-Ekbom Disease. This suggests that the term Restless Legs Syndrome may not be the most appropriate term to denote this nosological entity. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Phenotypic expansion of the supernumerary derivative (22) chromosome syndrome: VACTERL and Hirschsprung's disease.

    Science.gov (United States)

    Prieto, Juan C; Garcia, Nilda M; Elder, Frederick F; Zinn, Andrew R; Baker, Linda A

    2007-11-01

    Phenotypically healthy carriers of the balanced 11;22 translocation, the most frequent non-Robertsonian constitutional translocation known in human beings, are at risk of having a progeny with supernumerary derivative (22)t(11;22) syndrome [der(22) syndrome]. We present the cases of 2 male patients with supernumerary der(22) syndrome [47,XY,+der(22)t(11;22)(q23;q11.2)mat], yielding partial trisomy for 22pter-q11 and 11q23-qter. These cases expand the phenotype of the der(22) syndrome, with the first case highlighting the phenotypic overlap of VACTERL and the second adding Hirschsprung's disease and intestinal malrotation to the list of associated anorectal anomalies. Because der(22) syndrome and cat eye syndrome (partial tetrasomy of 22q11) share a similar region of extra dosage on 22q11 and both typically manifest an anorectal phenotype, a dosage-sensitive gene for anorectal anomalies may be present in this locus.

  8. [Stevens-Johnson syndrome and Hodgkin's disease: A fortuitous association or paraneoplastic syndrome?].

    Science.gov (United States)

    Schoeffler, A; Levy, E; Weinborn, M; Cuny, J-F; Schmutz, J-L; Barbaud, A; Cribier, B; Bursztejn, A-C

    2014-02-01

    Hodgkin's disease has been associated with a variety of cutaneous symptoms. We report two cases of Stevens-Johnson syndrome (SJS) associated with Hodgkin's disease. Case 1: a 22-year-old man was hospitalized for a second erythematous vesicular eruption with intense mucosal involvement. Histopathological examination confirmed the diagnosis of Stevens-Johnson syndrome. He also developed enlarged cervical lymph nodes that revealed Hodgkin's disease. The latter diagnosis was followed by two recurrent rashes. Treatment consisted of systemic chemotherapy. Complete remission was obtained with no signs of cutaneous recurrence after 24 months of regular follow-up. Case 2: a 29-year-old man was admitted for a generalized erythematous and bullous rash with intense mucosal involvement. Histopathological examination confirmed the diagnosis of Stevens-Johnson syndrome. He then developed muco-cutaneous icterus that was secondary to Hodgkin's disease. Under specific hematologic treatment, no cutaneous relapse was noticed. These cases illustrate the rare association of SSJ revealing Hodgkin's disease. In these cases, no evidence was found of infectious disease or drug-induced cutaneous effects. Only one case of toxic epidermal necrolysis associated with Hodgkin's disease had previously been reported. The link between both diseases may be immunosuppression induced by Hodgkin's disease, which could favor infection inducing SJS or secretion by tumor cells granulysin, a mediator responsible for damage to keratinocytes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Personalized gene silencing therapeutics for Huntington disease.

    Science.gov (United States)

    Kay, C; Skotte, N H; Southwell, A L; Hayden, M R

    2014-07-01

    Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non-selective silencing of both copies. Huntington disease (HD) is an autosomal dominant disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin gene (HTT). Silencing both expanded and normal copies of HTT may be therapeutically beneficial, but preservation of normal HTT expression is preferred. Allele-specific methods can selectively silence the mutant HTT transcript by targeting either the expanded CAG repeat or single nucleotide polymorphisms (SNPs) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of HD by CAG- and SNP-specific silencing approaches and review HD population genetics used to guide target identification in the patient population. Clinical implementation of allele-specific HTT silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Disease gene characterization through large-scale co-expression analysis.

    Directory of Open Access Journals (Sweden)

    Allen Day

    2009-12-01

    Full Text Available In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET.Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format. The size of Celsius makes UGET a powerful gene characterization tool. Using a small seed list of known cartilage-selective genes, UGET extended the list of known genes by identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested were validated by qPCR including the novel cartilage-specific genes SDK2 and FLJ41170. In addition, we retrospectively tested UGET and other gene expression based prioritization tools to identify disease-causing genes within known linkage intervals. We first demonstrated this utility with UGET using genetically heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric disorders and type 2 limb girdle muscular dystrophy (LGMD2 and then compared UGET to other gene expression based prioritization programs which use small but discrete and well annotated datasets. Finally, we observed a significantly higher gene correlation shared between genes in disease networks associated with similar complex or Mendelian disorders.UGET is an invaluable resource for a geneticist that permits the rapid inclusion of expression criteria from one to hundreds of genes in genomic intervals linked to disease. By using thousands of arrays UGET annotates and prioritizes genes better than other tools especially with rare tissue disorders or complex multi-tissue biological processes. This information can be critical in prioritization of candidate genes for sequence analysis.

  11. Posterior reversible encephalopathy syndrome in children with kidney disease

    Directory of Open Access Journals (Sweden)

    D N Gera

    2014-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinic-radiographic entity of heterogeneous etiologies that are grouped together because of similar findings on neuro-imaging and associated symptom complex of headache, vision loss, altered mentation, and seizures. Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure. This case series included 11 patients (8 males, 3 females, age 3-15 years of PRES during September 2010 to February 2012 out of a total 660 renal pediatric patients (1.66%. We studied their clinical profile, contributory factors, and outcome. Presenting symptoms were headache in 73%, dimness of vision or cortical blindness in 36%, seizures in 91%, and altered mentation in 55%. The associated renal diseases were acute renal failure (55%, chronic renal failure (9%, and 36% had normal renal function. The contributory factors were uncontrolled hypertension (100%, severe hypoproteinemia (9%, persistent hypocalcemia (9%, hemolytic uremic syndrome (36%, cyclosporine toxicity (9%, lupus nephritis (9%, high hematocrit (9%, and pulse methylprednisolone (9%. Brain imaging showed involvement of occipito-parietal area (100% and other brain areas (63%. All but one patient of hemolytic uremic syndrome had complete clinical neurological recovery in a week, and all had normal neurological imaging after 4-5 weeks. PRES is an underdiagnosed entity in pediatric renal disease patients. Associated hypertension, renal disease, and immunosuppressive treatment are important triggers. Early diagnosis and treatment of comorbid conditions is of prime importance for early reversal of syndrome.

  12. Variations in ORAI1 Gene Associated with Kawasaki Disease.

    Science.gov (United States)

    Onouchi, Yoshihiro; Fukazawa, Ryuji; Yamamura, Kenichiro; Suzuki, Hiroyuki; Kakimoto, Nobuyuki; Suenaga, Tomohiro; Takeuchi, Takashi; Hamada, Hiromichi; Honda, Takafumi; Yasukawa, Kumi; Terai, Masaru; Ebata, Ryota; Higashi, Kouji; Saji, Tsutomu; Kemmotsu, Yasushi; Takatsuki, Shinichi; Ouchi, Kazunobu; Kishi, Fumio; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Sato, Yoshitake; Honda, Akihito; Kobayashi, Hironobu; Sato, Junichi; Shibuta, Shoichi; Miyawaki, Masakazu; Oishi, Ko; Yamaga, Hironobu; Aoyagi, Noriyuki; Yoshiyama, Megumi; Miyashita, Ritsuko; Murata, Yuji; Fujino, Akihiro; Ozaki, Kouichi; Kawasaki, Tomisaku; Abe, Jun; Seki, Mitsuru; Kobayashi, Tohru; Arakawa, Hirokazu; Ogawa, Shunichi; Hara, Toshiro; Hata, Akira; Tanaka, Toshihiro

    2016-01-01

    Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca(2+)/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca(2+) release activated Ca(2+) (CRAC) channel mediating store-operated Ca(2+) entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair in-frame insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca(2+)/NFAT pathway in the pathogenesis of this disorder.

  13. A novel and de novo deletion in the OCRL1 gene associated with a severe form of Lowe syndrome.

    Science.gov (United States)

    Peces, Ramón; Peces, Carlos; de Sousa, Erika; Vega, Cristina; Selgas, Rafael; Nevado, Julián

    2013-12-01

    The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate (PIP2P) 5-phosphatase, is responsible for the phenotypic characteristics of the disease. We report a 22-year-old male with a severe form of OCRL syndrome, diagnosed on the basis of congenital cataracts, severe psychomotor and cognitive deficits, and renal tubular dysfunction without Fanconi syndrome. The patient presented low molecular weight proteinuria, nephrocalcinosis, nephrolithiasis, rickets, and growth retardation and developed progressive renal failure. Genetic analysis showed a novel and de novo deletion of exons 10-13 in the OCRL1 gene.

  14. A new mutation in the gene encoding mitochondrial seryl-tRNA synthetase as a cause of HUPRA syndrome.

    Science.gov (United States)

    Rivera, Henry; Martín-Hernández, Elena; Delmiro, Aitor; García-Silva, María Teresa; Quijada-Fraile, Pilar; Muley, Rafael; Arenas, Joaquín; Martín, Miguel A; Martínez-Azorín, Francisco

    2013-09-13

    HUPRA syndrome is a rare mitochondrial disease characterized by hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis. This syndrome was previously described in three patients with a homozygous mutation c.1169A > G (p.D390G) in SARS2, encoding the mitochondrial seryl-tRNA synthetase. Here we report the clinical and genetic findings in a girl and her brother. Both patients were clinically diagnosed with the HUPRA syndrome. Analysis of the pedigree identified a new homozygous mutation c.1205G > A (p.R402H) in SARS2 gene. This mutation is very rare in the population and it is located at the C-terminal globular domain of the homodimeric enzyme very close to p.D390G. Several data support that p.R402H mutation in SARS2 is a new cause of HUPRA syndrome.

  15. Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome.

    Science.gov (United States)

    Zimprich, A; Grabowski, M; Asmus, F; Naumann, M; Berg, D; Bertram, M; Scheidtmann, K; Kern, P; Winkelmann, J; Müller-Myhsok, B; Riedel, L; Bauer, M; Müller, T; Castro, M; Meitinger, T; Strom, T M; Gasser, T

    2001-09-01

    The dystonias are a common clinically and genetically heterogeneous group of movement disorders. More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far. These are DYT1, encoding torsin A and mutant in the early-onset generalized form, GCH1 (formerly known as DYT5), encoding GTP-cyclohydrolase I and mutant in dominant dopa-responsive dystonia, and TH, encoding tyrosine hydroxylase and mutant in the recessive form of the disease. Myoclonus-dystonia syndrome (MDS; DYT11) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles. Dystonia, usually torticollis and/or writer's cramp, occurs in most but not all affected patients and may occasionally be the only symptom of the disease. In addition, patients often show prominent psychiatric abnormalities, including panic attacks and obsessive-compulsive behavior. In most MDS families, the disease is linked to a locus on chromosome 7q21 (refs. 11-13). Using a positional cloning approach, we have identified five different heterozygous loss-of-function mutations in the gene for epsilon-sarcoglycan (SGCE), which we mapped to a refined critical region of about 3.2 Mb. SGCE is expressed in all brain regions examined. Pedigree analysis shows a marked difference in penetrance depending on the parental origin of the disease allele. This is indicative of a maternal imprinting mechanism, which has been demonstrated in the mouse epsilon-sarcoglycan gene.

  16. Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite kindred

    Energy Technology Data Exchange (ETDEWEB)

    Dow, E.; Cross, S.; Williamson, R. [St. Mary`s Hospital Medical School, London (United Kingdom); Mulligan, L.M. [Univ. of Cambridge, MA (United States); Lyonnet, S. [Hopital des Enfants Malades, Paris (France); Wolgemuth, D.J. [Columbia Univ., New York, NY (United States); Mascari, M.; Ladda, R. [Milton S. Hershey Medical Center, PA (United States)

    1994-10-15

    We have studied a large Mennonite kindred in which 20 members were affected with Hirschburg disease (HSCR), 5 of whom had one or more manifestations of Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest migration/differentiation, this large pedigree with apparent cosegregation of HSCR and WS2 offered an opportunity to search for linkage between these loci, candidate genes, and random DNA markers, particularly in view of recent discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung disease (c-ret). We have examined the following possible linked markers in 69 relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to ABO blood groups which have shown weak linkage to WS; and the {beta}1 GABA receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred was excluded, demonstrating that there is at least one further locus for HSCR other than c-ret. 45 refs., 1 fig., 3 tabs.

  17. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

    Science.gov (United States)

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. Copyright© Ferrata Storti

  18. Mapping gene associations in human mitochondria using clinical disease phenotypes.

    Directory of Open Access Journals (Sweden)

    Curt Scharfe

    2009-04-01

    Full Text Available Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects

  19. Predicting disease-related genes using integrated biomedical networks

    OpenAIRE

    Peng, Jiajie; Bai, Kun; Shang, Xuequn; Wang, Guohua; Xue, Hansheng; Jin, Shuilin; Cheng, Liang; Wang, Yadong; Chen, Jin

    2017-01-01

    Background Identifying the genes associated to human diseases is crucial for disease diagnosis and drug design. Computational approaches, esp. the network-based approaches, have been recently developed to identify disease-related genes effectively from the existing biomedical networks. Meanwhile, the advance in biotechnology enables researchers to produce multi-omics data, enriching our understanding on human diseases, and revealing the complex relationships between genes and diseases. Howeve...

  20. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

    OpenAIRE

    Spataro, Nino, 1984-; Rodríguez, Juan Antonio; Navarro i Cuartiellas, Arcadi, 1969-; Bosch Fusté, Elena

    2017-01-01

    Abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevan...

  1. Antiphospholipid Syndrome and Vascular Ischemic (Occlusive) Diseases: An Overview

    Science.gov (United States)

    2007-01-01

    Antiphospholipid syndrome (APS) is primarily considered to be an autoimmune pathological condition that is also referred to as "Hughes syndrome". It is characterized by arterial and/or venous thrombosis and pregnancy pathologies in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disease or secondary to a connective tissue disorder, most frequently systemic lupus erythematosus (SLE). Damage to the nervous system is one of the most prominent clinical constellations of sequelae in APS and includes (i) arterial/venous thrombotic events, (ii) psychiatric features and (iii) other non-thrombotic neurological syndromes. In this overview we compare the most important vascular ischemic (occlusive) disturbances (VIOD) with neuro-psychiatric symptomatics, together with complete, updated classifications and hypotheses for the etio-pathogenesis of APS with underlying clinical and laboratory criteria for optimal diagnosis and disease management. PMID:18159581

  2. Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome.

    Science.gov (United States)

    Clarke, S D

    2001-04-01

    This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the (n-3) family, play pivotal roles as "fuel partitioners" in that they direct fatty acids away from triglyceride storage and toward oxidation, and that they enhance glucose flux to glycogen. In doing this, PUFA may protect against the adverse symptoms of the metabolic syndrome and reduce the risk of heart disease. PUFA exert their beneficial effects by up-regulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously down-regulating genes encoding proteins of lipid synthesis. PUFA govern oxidative gene expression by activating the transcription factor peroxisome proliferator-activated receptor alpha. PUFA suppress lipogenic gene expression by reducing the nuclear abundance and DNA-binding affinity of transcription factors responsible for imparting insulin and carbohydrate control to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear abundance and expression of sterol regulatory element binding protein-1 and reduce the DNA-binding activities of nuclear factor Y, Sp1 and possibly hepatic nuclear factor-4. Collectively, the studies discussed suggest that the fuel "repartitioning" and gene expression actions of PUFA should be considered among criteria used in defining the dietary needs of (n-6) and (n-3) and in establishing the dietary ratio of (n-6) to (n-3) needed for optimum health benefit.

  3. Parkinson's Disease: Is It a Toxic Syndrome?

    Directory of Open Access Journals (Sweden)

    Seham A. Gad ELhak

    2010-01-01

    Full Text Available Parkinson's disease (PD is one of the neurodegenerative diseases which we can by certainty identify its pathology, however, this confidence disappeares when talking about the cause. A long history of trials, suggestions, and theories tried linking PD to a specific causation. In this paper, a new suggestion is trying to find its way, could it be toxicology? Can we—in the future—look to PD as an occupational disease, in fact, many clues point to the possible toxic responsibility—either total or partial—in causing this disease. Searching for possible toxic causes for PD would help in designing perfect toxic models in animals.

  4. Pain syndrome features in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Bril Е.М.

    2016-12-01

    Full Text Available Pain in Parkinson disease take the special place among all of disease symptoms due to it pathogenetics and clinical diversity. In spite of the plurality of resent studies, the majority of clinical practioners and neurologists didn't pay attention to significant decline of the quality of life in patients with Parkinson disease and pain disorders. This article was created with aim to summarize all important results of studies, focused on pain pathogenesis and clinical features on different stages of disease.

  5. Dissecting the phenotypes of Dravet syndrome by gene deletion.

    Science.gov (United States)

    Rubinstein, Moran; Han, Sung; Tai, Chao; Westenbroek, Ruth E; Hunker, Avery; Scheuer, Todd; Catterall, William A

    2015-08-01

    Neurological and psychiatric syndromes often have multiple disease traits, yet it is unknown how such multi-faceted deficits arise from single mutations. Haploinsufficiency of the voltage-gated sodium channel Nav1.1 causes Dravet syndrome, an intractable childhood-onset epilepsy with hyperactivity, cognitive deficit, autistic-like behaviours, and premature death. Deletion of Nav1.1 channels selectively impairs excitability of GABAergic interneurons. We studied mice having selective deletion of Nav1.1 in parvalbumin- or somatostatin-expressing interneurons. In brain slices, these deletions cause increased threshold for action potential generation, impaired action potential firing in trains, and reduced amplification of postsynaptic potentials in those interneurons. Selective deletion of Nav1.1 in parvalbumin- or somatostatin-expressing interneurons increases susceptibility to thermally-induced seizures, which are strikingly prolonged when Nav1.1 is deleted in both interneuron types. Mice with global haploinsufficiency of Nav1.1 display autistic-like behaviours, hyperactivity and cognitive impairment. Haploinsufficiency of Nav1.1 in parvalbumin-expressing interneurons causes autistic-like behaviours, but not hyperactivity, whereas haploinsufficiency in somatostatin-expressing interneurons causes hyperactivity without autistic-like behaviours. Heterozygous deletion in both interneuron types is required to impair long-term spatial memory in context-dependent fear conditioning, without affecting short-term spatial learning or memory. Thus, the multi-faceted phenotypes of Dravet syndrome can be genetically dissected, revealing synergy in causing epilepsy, premature death and deficits in long-term spatial memory, but interneuron-specific effects on hyperactivity and autistic-like behaviours. These results show that multiple disease traits can arise from similar functional deficits in specific interneuron types. © The Author (2015). Published by Oxford University Press on

  6. Support for an hypothesis linking Alzheimer`s disease and Down syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Geller, L.N.; Benjamin, M.B.; Dressler, D. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    A connection between Alzheimer`s disease (AD) and Down syndrome (trisomy 21) is indicated by the fact that Down syndrome individuals develop AD neuropathology by the third or fourth decade of life. One explanation for the connection between AD and Down syndrome would be that the overexpression of a gene or genes on chromosome 21 results in Alzheimer`s disease, the most likely candidate being the amyloid precursor protein (APP) gene. However, mutations in the APP gene have been found to be associated with only a very small percentage of familial AD cases. An alternative cause of some Alzheimer`s disease cases may be sporadic trisomy of chromosome 21, resulting from mutations or toxins that cause chromosome nondisjunction. Several predictions can be made based on this hypothesis. One prediction is that there should be more trisomy 21 in cells from AD individuals than from unaffected controls. Using quantitative fluorescence in situ hybridization to compare the number of trisomy chromosome 21 cells in cultured fibroblasts from AD and unaffected individuals, we have shown that there are a significantly larger number of trisomy 21 cells from AD individuals. Another prediction is that a defect in the mitotic spindle apparatus could be the underlying cause of the aneuploidy. Cultured lymphoblasts from AD and unaffected individuals were briefly exposed to the microtubule-disrupting agent colchicine. As assayed by the subsequent appearance of metaphase chromosomes showing centromere separation, cells from AD patients were significantly more sensitive to colchicine treatment compared to cells from unaffected individuals, supporting the prediction of an altered spindle apparatus. Finally, we would predict that both types of patients should share some physical symptoms. We have also found that AD, like Down`s patients, are hypersensitive to the effect of the cholinergic antagonist, tropicamide, on pupil dilation, which may serve as a diagnostic test for Alzheimer`s disease.

  7. Women with Polycystic Ovary Syndrome and Risk of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Blagojevic Iva Perovic

    2017-09-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is associated with reproductive and metabolic abnormalities. The aim of this study was to analyse risk of cardiovascular disease (CVD in PCOS, to define individual risk factors and assess their ability to predict risk.

  8. Clinical presentation & management of glomerular diseases: hematuria, nephritic & nephrotic syndrome.

    Science.gov (United States)

    Khanna, Ramesh

    2011-01-01

    Because the differential diagnosis for glomerulonephritis (GN) is broad, using a classification schema is helpful to narrow the causes of GN in a systematic manner. The etiology of glomerulonephritis can be classified by their clinical presentation (nephrotic, nephritic, rapidly progressive GN, chronic GN) or by histopathology. GN may be restricted to the kidney (primary glomerulonephritis) or be a secondary to a systemic disease (secondary glomerulonephritis). The nephrotic syndrome is defined by the presence of heavy proteinuria (protein excretion greater than 3.0 g/24 hours), hypoalbuminemia (less than 3.0 g/dL), and peripheral edema. Hyperlipidemia and thrombotic disease may be present. The nephritic syndrome is associated with hematuria and proteinuria and abnormal kidney function and carries poorer prognosis and is typically associated with hypertension. The predominant cause of the nephrotic syndrome in children is minimal change disease. The most common causes of nephritic syndrome are post infectious GN, IgA nephropathy and lupus nephritis. Chronic GN is slowly progressive and is associated with hypertension and gradual loss of kidney function. Treatment includes non-specific measure aimed at controlling hypertension, edema, proteinuria and disease modifying immunosuppression.

  9. Gamma Knife Radiosurgery for Cushing's Disease and Nelson's Syndrome

    Czech Academy of Sciences Publication Activity Database

    Marek, J.; Ježková, J.; Hána, V.; Kršek, M.; Liščák, R.; Vladyka, V.; Pecen, Ladislav

    2015-01-01

    Roč. 18, č. 3 (2015), s. 376-384 ISSN 1386-341X Institutional support: RVO:67985807 Keywords : Cushing's disease * Nelson's syndrome * Gamma knife surgery * Pituitary adenoma Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.407, year: 2015

  10. Addison's disease presenting as acute chest syndrome: Case report ...

    African Journals Online (AJOL)

    Addison's disease presenting as acute chest syndrome: Case report and review of literature. MR Akpa, OJ Odia. Abstract. No Abstract. Nigerian Journal of Medicine Vol. 15 (4) October-December 2006: 451-452. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  11. Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

    Science.gov (United States)

    2016-01-01

    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease. PMID:27915472

  12. Crohn's Disease Is Associated With Restless Legs Syndrome

    OpenAIRE

    Weinstock, Leonard B.; Bosworth, Brian P.; Scherl, Ellen J.; Li, Ellen; Iroku, Ugonna; Munsell, Melissa A.; Mullen, Gerald E.; Walters, Arthur S.

    2010-01-01

    Extraintestinal manifestations of Crohn's disease (CD) have not previously included the central nervous system (CNS). Restless legs syndrome (RLS) is a CNS disorder that is either idiopathic or secondary to a number of diseases. The aim of this study was to determine if RLS was associated with CD because both are associated with iron deficiency, inflammation, and bacterial overgrowth. Consecutive CD outpatients (N=272) were prospectively surveyed at 4 centers for criteria for RLS. Incidence (...

  13. Inflammation aggravates disease severity in Marfan syndrome patients.

    Directory of Open Access Journals (Sweden)

    Teodora Radonic

    Full Text Available BACKGROUND: Marfan syndrome (MFS is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-β and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-β and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-β were found especially in MFS patients with aortic root dilatation (124 pg/ml, when compared to MFS patients with normal aorta (10 pg/ml; p = 8×10(-6, 95% CI: 70-159 pg/ml. Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR = 0%, ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC = 1.8; 1.4; 1.5, FDR = 0% and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%. Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02 and increased number of CD8+ T-cells (p = 0.003 in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients.

  14. Metabolic syndrome in patients with ischemic heart disease

    International Nuclear Information System (INIS)

    Yasmin, S.; Naveed, T.; Shakoor, T.

    2008-01-01

    To determine the frequency of metabolic syndrome in patients with Ischemic Heart Disease (IHD). Cross-sectional, descriptive study. A total of 100 subjects with ischemic heart disease, fulfilling the inclusion criteria, were enrolled in the study. Demographic data (age and gender) and the 5 component conditions of the metabolic syndrome were noted. Subjects were physically assessed for the abdominal obesity, based on waist circumference. Fasting blood samples for glucose and lipid profile in first 24 hours after acute coronary insult were drawn and tested in central laboratory. Variables were processed for descriptive statistics. In this study population, 68% were male and 32% were female with mean age of 52 +-13.6 years in men and 56 +- 12.5 years in women. Frequency of metabolic syndrome was 32% in men and 28% in women. It increased with age. The highest rate of metabolic syndrome was in men diagnosed as STEMI (odds ratio: 3.39, 95% CI=1.36-8.41). Frequency of metabolic syndrome was high among the patients with IHD. It supports the potential for preventive efforts in persons with high-risk of IHD. (author)

  15. Angelman syndrome due to a termination codon mutation of the UBE3A gene.

    Science.gov (United States)

    Al-Maawali, Almundher; Machado, Jerry; Fang, Ping; Dupuis, Lucie; Faghfoury, Hannaneh; Mendoza-Londono, Roberto

    2013-03-01

    Angelman syndrome is a neurodevelopmental disorder characterized by global developmental delay, mental retardation, seizures, microcephaly, and severe speech delay. It may be caused by deletion of chromosome region 15q11.2 of the maternally inherited chromosome, mutations in the UBE3A gene, uniparental disomy, or imprinting defects. Most patients with this diagnosis have a severe phenotype, and a few have a mild form of the disease. We report a patient with a novel mutation in the UBE3A gene that consists of a deletion of the termination codon (c.2556-*+6del GTAAAACAAA) and results in an elongated protein E3 ubiquitin-protein ligase. Our patient has a mild phenotype compared with other patients in general and specifically to patients with UBE3A mutations. He has mild developmental delay, moderate speech delay, and no seizures. Recognition of this genotype-phenotype correlation will allow better genetic counseling to other patients with similar stop codon mutations.

  16. Metabolic syndrome, diabetes and atherosclerosis: Influence of gene-environment interaction

    Energy Technology Data Exchange (ETDEWEB)

    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud, Massa (Italy)

    2009-07-10

    Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of 'environmental cardiology'. Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of 'personalized intervention program'.

  17. HEREDITARY DISEASES AND SYNDROMES ACCOMPANIED BY FEBRILE CONVULSIONS: CLINICAL AND GENETIC CHARACTERISTICS AND DIAGNOSTIC PROCEDURES

    Directory of Open Access Journals (Sweden)

    E. L. Dadali

    2016-01-01

    Full Text Available The authors provide a review of the clinical and genetic characteristics of hereditary diseases and syndromes accompanied by febrile convulsions, which is illustrated by examples of their own observations. The paper sets forth the possibilities and limitations of using current methods for the molecular genetic diagnosis of idiopathic and symptomatic epilepsies. The most effective and less expensive technique of molecular genetic analysis is shown to be an exome sequencing test using the panels of genes responsible for the occurrence of diseases with simi1ar clinical symptoms. The paper also presents the structure of the panel of genes responsible for the occurrence of monogenic epilepsies, which has been designed at the Genomed Clinic and includes 448 genetic variants. It also determines the significance of using a chromosomal microarray analysis to diagnose both chromosomal and monogenic diseases accompanied by convulsions. 

  18. Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome.

    Directory of Open Access Journals (Sweden)

    Fei Yang

    Full Text Available Pulmonary arterial hypertension, also known as Ascites syndrome (AS, remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear.We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes pathways (Padj<0.05 regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group.Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression.

  19. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease

    OpenAIRE

    Mitra Souvik; Samanta Moumita; Sarkar Mihir; Chatterjee Sukanta

    2010-01-01

    Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination ...

  20. Molecular Testing of MECP2 Gene in Rett Syndrome Phenotypes in Indian Girls.

    Science.gov (United States)

    Lallar, Meenakshi; Rai, Archana; Srivastava, Priyanka; Mandal, Kausik; Gupta, Neerja; Kabra, Madhulika; Phadke, Shubha R

    2018-02-09

    To assess yield of MECP2 gene sequence variations analysis and large deletions in suspected cases of Rett syndrome. Descriptive study. Tertiary-care medical genetics center. Girls with neuroregression, postnatal microcephaly and signs and symptoms suggestive of classical and atypical Rett syndrome were classified into two groups. Group I consisted of girls with Classical and atypical Rett syndrome on basis on the Revised Rett Syndrome diagnostic criteria, 2010. Group II included girls with neuroregression and postnatal microcephaly and other Rett like features but not fulfilling the above criteria. Sanger sequencing of coding regions and large deletional analysis of MECP2 gene. Identification of mutation in MECP2 gene. Mutation in MECP2 gene was identified in 74% (14/19) in group I and none (0/17) in group II. The mutation detection rate was 92% (13/14) in group I classical Rett syndrome girls (2 with large deletions identified with Multiplex ligation dependent probe amplification) and 20% (1/5) in group I atypical Rett syndrome girls. One novel MECP2 sequence variation was identified in group I classical Rett syndrome. The yield of the mutation detection in MECP2 is much higher in classical than in atypical Rett syndrome. In girls with some Rett like features, but not fulfilling revised Rett syndrome diagnostic criteria, mutation testing for MECP2 gene has a low yield.

  1. Genetic analysis of the CHD7 gene in Korean patients with CHARGE syndrome.

    Science.gov (United States)

    Cho, Hyun-Ju; Song, Mee Hyun; Choi, Soo-Young; Kim, Jeongho; Lee, Jinwook; Kim, Un-Kyung; Bok, Jinwoong; Choi, Jae Young

    2013-04-01

    CHARGE syndrome is an autosomal dominant congenital disorder known to be caused by the haploinsufficiency of the CHD7 gene. Heterozygous mutations in the CHD7 gene have been identified in approximately 60-70% of patients clinically diagnosed with CHARGE syndrome. Although there have been many reports on the mutational spectrum of the CHD7 gene in patients with CHARGE syndrome worldwide, little is known about this syndrome in the Korean population. In this study, three Korean patients with CHARGE syndrome including one patient with Patau syndrome were evaluated for genetic analysis of the CHD7 gene using direct sequencing of all 38 exons and the flanking intronic regions. One nonsense and two novel missense mutations were identified in the CHD7 gene. Clinical symptoms caused by the missense mutations were much milder compared to the nonsense mutation, confirming the previously determined genotype-phenotype correlation in CHARGE syndrome. Our study demonstrates the importance of mutational screening of CHD7 in patients who have been diagnosed with other syndromes but display clinical features of CHARGE syndrome. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. ABCD syndrome is caused by a homozygous mutation in the EDNRB gene

    NARCIS (Netherlands)

    Verheij, JBGM; Kunze, J; Osinga, J; van Essen, AJ; Hofstra, RMW

    2002-01-01

    ABCD syndrome is an autosomal recessive syndrome characterized by albinism, black lock, cell migration disorder of the neurocytes of the gut (Hirschsprung disease [HSCR]), and deafness. This phenotype clearly overlaps with the features of the Shah-Waardenburg syndrome, comprising sensorineural

  3. Decompression syndrome (Caisson disease) in an Indian diver.

    Science.gov (United States)

    Phatak, Uday A; David, Eric J; Kulkarni, Pravin M

    2010-07-01

    Acute decompression syndrome (Caisson's disease) is an acute neurological emergency in divers. It is caused due to release of nitrogen gas bubbles that impinge the blood vessels of the spinal cord and brain and result in severe neurodeficit. There are very few case reports in Indian literature. There are multiple factors in the pathogenesis of Acute decompression syndrome (Caisson's disease) such as health problems in divers (respiratory problems or congenital heart diseases like atrial septal defect, patent ductus arteriosus etc), speed of ascent from the depth and habits like smoking that render divers susceptible for such neurological emergency. Usually, immediate diagnosis of such a condition with MRI is not possible in hospitals in the Coastal border. Even though, MRI is performed, it has very low specificity and sensitivity. Facilities like hyperbaric oxygen treatment are virtually non-existent in these hospitals. Therefore, proper education of the divers and appropriate preventive measures in professional or recreational divers is recommended.

  4. Restless Legs Syndrome: Current Concepts about Disease Pathophysiology

    Science.gov (United States)

    Koo, Brian B.; Bagai, Kanika; Walters, Arthur S.

    2016-01-01

    Background In the past few decades, much has been learned about the pathophysiology of restless legs syndrome (RLS). Investigators have studied neuropathology, imaging, electrophysiology, and genetics of RLS, identifying brain regions and biological systems affected in RLS. This manuscript will review RLS pathophysiology literature, examining the RLS state through consideration of the neuroanatomy, then the biological, organ, and genetic systems. Methods Pubmed (1966 to April 2016) was searched for the term “restless legs syndrome” cross-referenced with “pathophysiology,” “pathogenesis,” “pathology,” or “imaging.” English language papers were reviewed. Studies that focused on RLS in relation to another disease were not reviewed. Results Although there are no gross structural brain abnormalities in RLS, widespread brain areas are activated, including the pre- and post-central gyri, cingulate cortex, thalamus, and cerebellum. Pathologically, the most consistent finding is striatal iron deficiency in RLS patients. A host of other biological systems are also altered in RLS, including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems. Polymorphisms in genes including BTBD9 and MEIS1 are associated with RLS. Discussion RLS is a neurologic sensorimotor disorder that involves pathology, most notably iron deficiency, in motor and sensory brain areas. Brain areas not subserving movement or sensation such as the cingulate cortex and cerebellum are also involved. Other biological systems including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems are involved. Further research is needed to determine which of these anatomic locations or biological systems are affected primarily, and which are affected in a secondary response. PMID:27536462

  5. Restless Legs Syndrome: Current Concepts about Disease Pathophysiology

    Directory of Open Access Journals (Sweden)

    Brian B. Koo

    2016-07-01

    Full Text Available Background: In the past few decades, much has been learned about the pathophysiology of restless legs syndrome (RLS. Investigators have studied neuropathology, imaging, electrophysiology, and genetics of RLS, identifying brain regions and biological systems affected in RLS. This manuscript will review RLS pathophysiology literature, examining the RLS state through consideration of the neuroanatomy, then the biological, organ, and genetic systems. Methods: Pubmed (1966 to April 2016 was searched for the term “restless legs syndrome” cross-referenced with “pathophysiology,” “pathogenesis,” “pathology,” or “imaging.” English language papers were reviewed. Studies that focused on RLS in relation to another disease were not reviewed. Results: Although there are no gross structural brain abnormalities in RLS, widespread brain areas are activated, including the pre- and post-central gyri, cingulate cortex, thalamus, and cerebellum. Pathologically, the most consistent finding is striatal iron deficiency in RLS patients. A host of other biological systems are also altered in RLS, including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems. Polymorphisms in genes including BTBD9 and MEIS1 are associated with RLS. Discussion: RLS is a neurologic sensorimotor disorder that involves pathology, most notably iron deficiency, in motor and sensory brain areas. Brain areas not subserving movement or sensation such as the cingulate cortex and cerebellum are also involved. Other biological systems including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems are involved. Further research is needed to determine which of these anatomic locations or biological systems are affected primarily, and which are affected in a secondary response.

  6. [Allgrove syndrome (triple A). Finding of a mutation not described in the AAAS gene].

    Science.gov (United States)

    Capataz Ledesma, M; Méndez Pérez, P; Rodríguez López, R; Galán Gómez, E

    2013-02-01

    Allgrove syndrome (triple A) is a rare autosomal recessive disease. The classic triad includes, congenital adrenal insufficiency due to ACTH resistance, achalasia of the cardia and alacrimia. Neurological abnormalities are associated with autonomic neuropathy, sensory and motor defects, deafness, mental retardation, Parkinsonism and dementia. The gene responsible is the ADRACALIN or AAAS encoding a protein called ALADIN. We report a case of a 19 year-old male, assessed when he was 10 years old in our department due to suspected storage disease. Mild mental and language retardation, hypernasal voice, sensory-motor neuropathy with autonomic involvement and signs of spastic paraparesis, alacrimia. gastroesophageal reflux, and achalasia. Molecular studies showed to mutations, the undescribed p.Tyr 19 Cys, and IVS14 +1 G. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  7. On the origins of Mendelian disease genes in man: the impact of gene duplication.

    Science.gov (United States)

    Dickerson, Jonathan E; Robertson, David L

    2012-01-01

    Over 3,000 human diseases are known to be linked to heritable genetic variation, mapping to over 1,700 unique genes. Dating of the evolutionary age of these disease-associated genes has suggested that they have a tendency to be ancient, specifically coming into existence with early metazoa. The approach taken by past studies, however, assumes that the age of a disease is the same as the age of its common ancestor, ignoring the fundamental contribution of duplication events in the evolution of new genes and function. Here, we date both the common ancestor and the duplication history of known human disease-associated genes. We find that the majority of disease genes (80%) are genes that have been duplicated in their evolutionary history. Periods for which there are more disease-associated genes, for example, at the origins of bony vertebrates, are explained by the emergence of more genes at that time, and the majority of these are duplicates inferred to have arisen by whole-genome duplication. These relationships are similar for different disease types and the disease-associated gene's cellular function. This indicates that the emergence of duplication-associated diseases has been ongoing and approximately constant (relative to the retention of duplicate genes) throughout the evolution of life. This continued until approximately 390 Ma from which time relatively fewer novel genes came into existence on the human lineage, let alone disease genes. For single-copy genes associated with disease, we find that the numbers of disease genes decreases with recency. For the majority of duplicates, the disease-associated mutation is associated with just one of the duplicate copies. A universal explanation for heritable disease is, thus, that it is merely a by-product of the evolutionary process; the evolution of new genes (de novo or by duplication) results in the potential for new diseases to emerge.

  8. Periodontal disease in a patient with Prader-Willi syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Kitamura Masahiro

    2011-07-01

    Full Text Available Abstract Introduction Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare. Case presentation We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution. Conclusions Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.

  9. Periodontal disease in a patient with Prader-Willi syndrome: a case report.

    Science.gov (United States)

    Yanagita, Manabu; Hirano, Hiroyuki; Kobashi, Mariko; Nozaki, Takenori; Yamada, Satoru; Kitamura, Masahiro; Murakami, Shinya

    2011-07-28

    Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare. We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution. Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.

  10. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

    Directory of Open Access Journals (Sweden)

    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  11. [Is the metabolic syndrome a new childhood disease?].

    Science.gov (United States)

    Janner, M; Mullis, P E; Flück, C E

    2006-03-29

    Overweight and obesity in children and adolescents have become a major public health problem in recent years throughout the world. The medical consequences of obesity may manifest as an increase in the prevalence of the metabolic syndrome in children and adolescents putting them at increased risk for future cardiovascular diseases. Obesity can cause insulin resistance and might disturb glucose homeostasis eventually leading to type 2 diabetes in susceptible patients. Insulin resistance is also involved in the pathogenesis of dyslipidemia in obese children characteristically presenting as hypertriglyceridemia and low HDL cholesterol. Even elevated blood pressure might be present in obese kids. Here we present a 12-year-old boy diagnosed with the metabolic syndrome. The diagnostic criteria of the metabolic syndrome in children and adolescents are discussed. Thoughts about pathophysiology and therapeutic options are offered.

  12. Kniest disease with Pierre Robin syndrome and hydrocephalus

    International Nuclear Information System (INIS)

    Silengo, M.C.; Davi, G.F.; Bianco, R.; DeMarco, A.; Franceschini, P.

    1983-01-01

    A 3-month-old male infant with clinical and radiological features of Kniest disease is reported. Additional findings were severe Pierre Robin syndrome and external hydrocephalus. The patient was retarded in mental and motor development. He died at 4 months of age from the complications of tracheostomy. The parents were both normal clinically and radiologically, thus the disease in the child was presumably due to a new mutation. The reported familial cases of Kniest disease suggest autosomal dominant inheritance. The differential diagnosis is discussed in detail. (orig.)

  13. Pathogenetic relationship between coronary heart disease and osteopenic syndrome

    Directory of Open Access Journals (Sweden)

    N. S. Mykhailovskaya

    2015-02-01

    Full Text Available The importance of the comorbidity problem of coronary heart disease and osteoporosis is caused by the rising prevalence, lack of early detection, prevention, severe complications and significant impact on the quality of life of the patients. Aim. In order to compile and submit a current point of view on the pathogenetic relationship between the coronary heart disease and the osteopenic syndrome we reviewed specialized literature. Conclusion. We established that coronary heart disease and osteoporosis have common mechanisms of progression involving a cascade of proinflammatory cytokines, osteoprotegerin, endothelial dysfunction, estrogen, calcium deficiency, the renin-angiotensin-aldosterone and sympathetic nervous system.

  14. The Acquired Immunedeficiency Syndrome and related diseases

    African Journals Online (AJOL)

    HTLV-III are helpful but are not available. Other investigations may be required depending on clinical findings to exclude other diseases and confirm opportunistic infection. •. Treatment. There is no specific treatment for AIDS at present. Infections detected in such patie~ts, eg oral candidiasis or T.B., should be treated m the.

  15. Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease.

    Science.gov (United States)

    Hackman, Kathryn L; Davis, Anna L; Curnow, Paul A; Serpell, Jonathan W; McLean, Catriona A; Topliss, Duncan J

    2010-01-01

    To report a case of Cushing syndrome due to apparently sporadic primary pigmented nodular adrenal disease in a young woman. We describe the clinical, biochemical, radiologic, and histologic findings of Cushing syndrome due to the rare condition of primary pigmented nodular adrenal disease. A 30-year-old woman presented with a 2-year history of worsening itch without rash over her shoulders and arms and weight gain, particularly around the abdomen and face. Careful questioning did not elicit any history of exogenous glucocorticoid use (systemic or topical), including hydrocortisone. On examination, the patient had a slightly rounded and plethoric face, a small buffalo hump, central adiposity, and thin skin with a few small striae on her inner thighs. No features of the Carney complex were observed. Investigations showed hypercortisolism with suppressed corticotropin and normal adrenal imaging despite documentation of enlarged adrenal glands at removal. High-dose dexamethasone administration was followed by a decrease in urinary free cortisol excretion rather than a paradoxical rise as previously reported in primary pigmented nodular adrenal disease. No mutations were detected in the PRKAR1A gene. Primary pigmented nodular adrenal disease should be suspected in patients with corticotropin-independent Cushing syndrome who have normal adrenal imaging. The role of genetic testing in apparently sporadic cases is not established, but cumulative experience may be helpful in defining the frequency of PRKAR1A mutations.

  16. Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.

    Science.gov (United States)

    Crowder, L A; Yedlin, V A; Weinstein, E R; Kortte, K B; Aucott, J N

    2014-09-01

    A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  17. [Mendelian arterial diseases. Pseudoxanthoma elasticum, Ehlers-Danlos vascular syndrome, Rendu-Osler disease].

    Science.gov (United States)

    Perdu, J

    2003-11-01

    Understanding the features of the various hereditary vascular pathologies allows consideration and confirmation of the diagnosis, and a search for treatable hidden disorders, avoiding harmful investigations, initiating follow up, performing family investigations and providing genetic counselling. Pseudoxanthoma elasticum must be considered in the presence of calcified distal arteriopathy of the lower limbs in a young subject without any other aetiological aspects. Cutaneous or mucosal lesions confirmed on histological examination, angioid streaks at the back of the eye and a family history support the diagnosis, which is confirmed by showing pathogenic mutations of the ABCC6 gene. It is then important to search for a peripheral disorder in other arterial territory, a low grade coronaropathy, hypertension and an endocardial disorder. Prescription of antithrombotics must be made carefully because of the risk of gastro-intestinal haemorrhage. Vascular Ehlers-Danlos syndrome is suspected in a subject less than 30 years old with diffuse aneurysmal disease, spontaneous arterial rupture or dissection, a carotido-cavernous fistula or early onset varices. Demonstrating an ecchymotic tendency or an acrogeric morphology, especially in a familial context, warrants cutaneous biopsy for anatomopathological examination and fibroblast culture for a study of the C0L3A1 gene. When the diagnosis is suggested, it is advisable to prohibit any arterial puncture, cold surgery or gastro-intestinal endoscopy. The search for aneurysmal lesions must be performed by non-invasive imaging. The therapeutic management requires specialised teams. The combination of repeated epistaxis, muco-cutaneous telangectasia and similar characteristics in a family suggests the diagnosis of Osler-Weber-Rendu disease. The search for iron deficiency, gastro-intestinal bleeds and pulmonary, hepatic or cerebral arterio-venous malformations is then necessary. Besides skilled endovascular management when indicated

  18. Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

    Science.gov (United States)

    Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

    2009-01-01

    Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

  19. The SPINK gene family and celiac disease susceptibility

    NARCIS (Netherlands)

    Wapenaar, M.C.; Monsuur, A.J.; Poell, J.; Slot, R. van 't; Meijer, J.W.R.; Meijer, G.A.; Mulder, C.J.; Mearin, M.L.; Wijmenga, C.

    2007-01-01

    The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

  20. The SPINK gene family and celiac disease susceptibility

    NARCIS (Netherlands)

    Wapenaar, Martin C.; Monsuur, Alienke J.; Poell, Jos; Slot, Ruben Van 't; Meijer, Jos W. R.; Meijer, Gerrit A.; Mulder, Chris J.; Mearin, Maria Luisa; Wijmenga, Cisca

    The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

  1. Syndromes and Disorders Associated with Omphalocele (III: Single Gene Disorders, Neural Tube Defects, Diaphragmatic Defects and Others

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-06-01

    Full Text Available Omphalocele can be associated with single gene disorders, neural tube defects, diaphragmatic defects, fetal valproate syndrome, and syndromes of unknown etiology. This article provides a comprehensive review of omphalocele-related disorders: otopalatodigital syndrome type II; Melnick–Needles syndrome; Rieger syndrome; neural tube defects; Meckel syndrome; Shprintzen–Goldberg omphalocele syndrome; lethal omphalocele-cleft palate syndrome; cerebro-costo-mandibular syndrome; fetal valproate syndrome; Marshall–Smith syndrome; fibrochondrogenesis; hydrolethalus syndrome; Fryns syndrome; omphalocele, diaphragmatic defects, radial anomalies and various internal malformations; diaphragmatic defects, limb deficiencies and ossification defects of skull; Donnai–Barrow syndrome; CHARGE syndrome; Goltz syndrome; Carpenter syndrome; Toriello–Carey syndrome; familial omphalocele; Cornelia de Lange syndrome; C syndrome; Elejalde syndrome; Malpuech syndrome; cervical ribs, Sprengel anomaly, anal atresia and urethral obstruction; hydrocephalus with associated malformations; Kennerknecht syndrome; lymphedema, atrial septal defect and facial changes; and craniosynostosis- mental retardation syndrome of Lin and Gettig. Perinatal identification of omphalocele should alert one to the possibility of omphalocele-related disorders and familial inheritance and prompt a thorough genetic counseling for these disorders.

  2. Anton's syndrome due to cerebrovascular disease: a case report

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    Maddula Mohana

    2009-09-01

    Full Text Available Abstract Introduction Anton's syndrome describes the condition in which patients deny their blindness despite objective evidence of visual loss, and moreover confabulate to support their stance. It is a rare extension of cortical blindness in which, in addition to the injury to the occipital cortex, other cortical centres are also affected, with patients typically behaving as if they were sighted. Case presentation We present a case report of an 83-year-old white woman with cortical blindness as a result of bilateral occipital lobe infarcts. Despite her obvious blindness, illustrated by her walking into objects, the patient expressed denial of visual loss and demonstrated confabulation in her accounts of her surroundings, consistent with a diagnosis of Anton's syndrome. Conclusions A suspicion of cortical blindness and Anton's syndrome should be considered in patients with atypical visual loss and evidence of occipital lobe injury. Cerebrovascular disease is the most common cause of Anton's syndrome, as in our patient. However, any condition that may result in cortical blindness can potentially lead to Anton's syndrome. Recovery of visual function will depend on the underlying aetiology, with cases due to occipital lobe infarction after cerebrovascular events being less likely to result in complete recovery. Management in these circumstances should accordingly focus on secondary prevention and rehabilitation.

  3. Direct immunofluorescence testing in the diagnosis of immunobullous disease, collagen vascular disease, and vascular injury syndromes.

    Science.gov (United States)

    Magro, Cynthia M; Roberts-Barnes, Jennifer; Crowson, A Neil

    2012-10-01

    Direct and indirect immunofluorescence (IF) plays a role in the evaluation of immunobullous diseases and their mimics, and in the investigation of vascular injury syndromes and autoimmune connective tissue disease (CTD). IF mapping may be an important adjunct in the assessment of congenital epidermolysis bullosa syndromes and in Alport disease, in which antibodies are directed at certain components of the basement membrane zone to assay for their deficiency. In many cases of immunobullous and autoimmune CTDs, correlation with direct IF results is useful and often decisive in lesional evaluation and thus in patient management. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Altered expression of circadian clock genes in polyglandular autoimmune syndrome type III.

    Science.gov (United States)

    Angelousi, Anna; Nasiri-Ansari, Narjes; Spilioti, Eliana; Mantzou, Emilia; Kalotyxou, Vasiliki; Chrousos, George; Kaltsas, Gregory; Kassi, Eva

    2018-01-01

    Circadian timing system is a highly conserved, ubiquitous molecular "clock" which creates internal circadian rhythmicity. Dysregulation of clock genes expression is associated with various diseases including immune dysregulation. In this study we investigated the circadian pattern of Clock-related genes in patients with polyglandular autoimmune syndrome type III (PAS type III). Nineteen patients diagnosed with PAS type III and 12 healthy controls were enrolled. mRNA and protein expression of Clock-related genes (CLOCK, BMAL1, ROR and Per-1,-2,-3), as well as the GR-a and the GILZ genes were determined by real-time quantitative PCR and western blot analysis from blood samples drawn at 8 pm and 8am. Serum cortisol and TSH, as well as plasma ACTH, were measured by chemiluminescence. There were no statistical significant differences in the metabolic profile, cortisol, ACTH and TSH levels between patients and controls. Patients with PAS type III expressed higher transcript levels of CLOCK, BMAL1 and Per-1 in the evening than in the morning (p = 0.03, p = 0.029, p = 0.013, respectively), while the ratios (R pm/am ) of GR-a, CLOCK, BMAL1, and Per-3 mRNA levels were statistically different between patients and controls. Cortisol circadian variation (F pm/am ) was positively correlated with GILZ mRNA circadian pattern (R pm/am ) in the patient group and with the GR-a mRNA (R pm/am ) in the control group. Our findings suggest that there is an aberrant circadian rhythm of Clock-related genes in patients with PAS type III. The disruption of the expression of 4 circadian Clock-related genes could indicate a possible association with the pathogenesis of the disease.

  5. Novel mutations in PRG4 gene in two Indian families with camptodactyly-arthropathy- coxa vara- pericarditis (CACP syndrome

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    Rajashree S Nandagopalan

    2014-01-01

    Full Text Available Background & objectives: Camptodactyly - arthropathy- coxa vara- pericarditis (CACP syndrome is an autosomal recessive disorder caused by mutations in the PRG4 (proteoglycan 4 gene. Hallmarks of the syndrome include congenital or early-onset camptodactyly and arthropathy with synovial hyperplasia, progressive coxa vara deformity and non-inflammatory pericardial effusions. Till date only around 25 pathogenic mutations have been reported in this gene and none have been reported from India. We report here the mutations in the PRG4 gene in three patients of CACP from two unrelated families from India. Methods: Molecular genetic studies were done for the three patients with the CACP syndrome, from two unrelated Indian families, through sequence analysis of all coding exons and the exon-intron boundaries of the PRG4 gene. Results: Two novel frame-shift deletion mutations leading to premature protein termination were found. One patient was identified to be homozygous for a 2 base pair deletion in exon 6 (c.2645_2646delGA and the two affected siblings from the other family were found to be homozygous for a 4 base pair deletion in exon 6 (c.2883_2886delAAGA. Conclusions: This is perhaps the first report of PRG4 mutations from India. Further mutation studies in Indian CACP cases will help to determine the mutation spectrum of the PRG4 gene in the Indian population and also help to further elucidate the molecular pathology and the genotype-phenotype correlation of this rare disease.

  6. Evolutionary signatures amongst disease genes permit novel methods for gene prioritization and construction of informative gene-based networks.

    Directory of Open Access Journals (Sweden)

    Nolan Priedigkeit

    2015-02-01

    Full Text Available Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC, is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting "disease map" network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks.

  7. Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations.

    Science.gov (United States)

    Sen, Ethan S; Dean, Philip; Yarram-Smith, Laura; Bierzynska, Agnieszka; Woodward, Geoff; Buxton, Chris; Dennis, Gemma; Welsh, Gavin I; Williams, Maggie; Saleem, Moin A

    2017-12-01

    There are many single-gene causes of steroid-resistant nephrotic syndrome (SRNS) and the list continues to grow rapidly. Prompt comprehensive diagnostic testing is key to realising the clinical benefits of a genetic diagnosis. This report describes a bespoke-designed, targeted next-generation sequencing (NGS) diagnostic gene panel assay to detect variants in 37 genes including the ability to identify copy number variants (CNVs). This study reports results of 302 patients referred for SRNS diagnostic gene panel analysis. Phenotype and clinical impact data were collected using a standard proforma. Candidate variants detected by NGS were confirmed by Sanger sequencing/Multiplex Ligation-dependent Probe Amplification with subsequent family segregation analysis where possible. Clinical presentation was nephrotic syndrome in 267 patients and suspected Alport syndrome (AS) in 35. NGS panel testing determined a likely genetic cause of disease in 44/220 (20.0%) paediatric and 10/47 (21.3%) adult nephrotic cases, and 17/35 (48.6%) of haematuria/AS patients. Of 71 patients with genetic disease, 32 had novel pathogenic variants without a previous disease association including two with deletions of one or more exons of NPHS1 or NPHS2 . Gene panel testing provides a genetic diagnosis in a significant number of patients presenting with SRNS or suspected AS. It should be undertaken at an early stage of the care pathway and include the ability to detect CNVs as an emerging mechanism for genes associated with this condition. Use of clinical genetic testing after diagnosis of SRNS has the potential to stratify patients and assist decision-making regarding management. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Behcet's disease in acquired immune deficiency syndrome

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    Beenish Siddiqui

    2016-01-01

    Full Text Available HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.

  9. Identification of four novel mutations of the WFS1 gene in Iranian Wolfram syndrome pedigrees.

    Science.gov (United States)

    Ghahraman, Martha; Abbaszadegan, Mohammad Reza; Vakili, Rahim; Hosseini, Sousan; Fardi Golyan, Fatemeh; Ghaemi, Nosrat; Forghanifard, Mohammad Mahdi

    2016-12-01

    Wolfram syndrome is a rare neurodegenerative disorder with an autosomal recessive pattern of inheritance characterized by various clinical manifestations. The related gene, WFS1, encodes a transmembrane glycoprotein, named wolframin. Genetic analyses demonstrated that mutations in this gene are associated with WS type 1. Our aim in this study was to sequence WFS1 coding region in Iranian Wolfram syndrome pedigrees. Genomic DNA was extracted from peripheral blood of 12 WS patients and their healthy parents. Exons 2-8 and the exon-intron junctions of WFS1 were sequenced. DNA sequences were compared to the reference using Sequencher software. Molecular analysis of WFS1 revealed six different mutations. Four novel and two previously reported mutations were identified. One novel mutation, c.1379_1381del, is predicted to produce an aberrant protein. A second novel mutation, c.1384G > T, encodes a truncated protein. Novel mutation, c.1097-1107dup (11 bp), causes a frameshift which results in a premature stop codon. We screened for the novel missense mutation, c.1010C > T, in 100 control alleles. This mutation was not found in any of the healthy controls. Our study increased the spectrum of WFS1 mutations and supported the role of WFS1 in susceptibility to WS. We hope that these findings open new horizons to future molecular investigations which may help to prevent and treat this devastating disease.

  10. Genetic mapping of the gene for Usher syndrome: Linkage analysis in a large Samaritan kindred

    Energy Technology Data Exchange (ETDEWEB)

    Bonne-Tamir, B.; Korostishevsky, M.; Kalinsky, H.; Seroussi, E.; Beker, R.; Weiss, S. (Sackler Faculty of Medicine, Ramat-Aviv (Israel)); Godel, V. (Ichilov Hospital, Tel-Aviv (Israel))

    1994-03-01

    Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed. 35 refs., 2 figs., 6 tabs.

  11. Genotyping Rs2274625 Marker in NPHS2 Gene Associated with Nephrotic Syndrome in Isfahan Population

    Directory of Open Access Journals (Sweden)

    L Esmaili Chamgordani

    2015-12-01

    Full Text Available Introduction: Nephrotic syndrome (NS is a genetic disease belonging to a heterogeneous group of glomerular disorders, which mainly occurs within the children. Linkage analysis using single nucleotide polymorphisms (SNP is used as an indirect method in molecular diagnosis of the disease. A large number of SNP markers have been introduced in NPHS2gene in the available electronic databases. Method: In the present study, the genotype and informative status of rs2274625 marker in NPHS2 genewas investigated in 120 unrelated healthy individuals using Tetra-primer ARMS PCR technique and newly designed primers. Allelic frequency and presence of Hardy Weinberg Equilibrium (HWE was estimated using GenePop website. Furthermore, PowerMarker software was utilized in order to compute the index of polymorphism information content (PIC. Results: The study results indicated allele frequency of 97% and 3% for C and T alleles, respectively, in regard with rs2274625 marker within Isfahan population. Moreover, the PIC for the rs2274625 marker was 0.5%, and HWE revealed the equilibruim of the study population in regard with the related marker. Conclusion: As the study findings indicated, rs2274625 could be introduced as an SNP marker in the linkage analysis in order to molecularly trace NPHS2 gene mutations in molecular NS diagnosis in Isfahan population as a representative sample of the Iranian population.

  12. Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion - preliminary report.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Webb, Muriel

    2008-10-01

    There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

  13. Hyperhemolysis Syndrome without Underlying Hematologic Disease

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    Lauren Anne Eberly

    2015-01-01

    Full Text Available Introduction. Hyperhemolysis is characterized by a life-threatening hemolytic transfusion reaction, with hemoglobin (Hb and hematocrit (Hct dropping markedly lower than before transfusion. This phenomenon, commonly described in sickle cell disease, is a rare occurrence in patients without hemoglobinopathies. Case Report. A 55-year-old male presented to the hospital after a motorcycle crash and received 10 units of cross-matched blood for active bleeding. The patient was blood group O, with a negative antibody screen. Ten days later, he represented complaining of dyspnea and was found to have a hematocrit of 12%. The direct antiglobulin test was positive for anti-immunoglobin G and complement. Indirect antiglobulin test was positive for anti-Jka alloantibodies. The presence of Jka antigen was revealed in one unit of previously transfused blood; patient’s RBCs were negative for the Jka antigen. Laboratory data demonstrated findings consistent with DHTR, as well as reticulopenia and elevated ferritin levels. He continued to show signs of active hemolysis, requiring a total of 4 subsequent units of pRBCs. Each transfusion precipitated a drop in Hb and Hct to levels lower than before transfusion; once transfusions were held, the patient slowly recovered. Discussion. Hyperhemolysis in the setting of a DHTR can occur in patients without hematologic disease.

  14. Polycystic Ovary Syndrome and the Relationship of Cardiovascular Disease Risk

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    Evrim Çakır

    2013-06-01

    Full Text Available Polycystic ovary syndrome (PCOS is a common endocrine disorder affecting at least 5-10% of women of reproductive age. PCOS is characterized by hyperandrogenism, menstrual disturbance, anovulation, infertility and obesity and, also associated with increased number of cardiovascular risk factors and early atherosclerosis. Hyperinsulinemia is a frequent finding in PCOS patients and has cause-and-effect relationship with low-grade chronic inflammation and increased risk of cardiovascular disease. Turk Jem 2013; 17: 33-7

  15. Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

    Science.gov (United States)

    Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

    2009-01-01

    Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

  16. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

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    Xia Wang

    Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

  17. Investigation of Monnose-Binding Lectin gene Polymorphism in Patients with Erythema Multiforme, Stevens-Johnson Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Overlap Syndrome

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    Sevil Toka

    2012-09-01

    Full Text Available Objective: Monnose-Binding lectin (MBL appears to play an important role in the immune system. The genetic polymorphisms in the MBL2 gene can result in a reduction of serum levels, leading to a predisposition to recurrent infection. The aim of this study is to investigate the influence of a polymorphism in codon 54 of the MBL2 gene on the susceptibility to Erythema Multiforme, Stevens-Johnson Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Overlap Syndrome (EM, SJS and SJS/TEN overlap syndrome. Material and Methods: Our study included 64 patients who were clinically and/or histopathologically diagnosed with EM, SJS, and SJS/TEN overlap syndrome and 66 healthy control subjects who were genotyped for the MBL2 gene codon 54 polymorphism using the PCR-RFLP method. For all statistical analyses, the level of significance was set at p<0.05. Results: The prevalence of the B allele was 18% in the EM, SJS and SJS/TEN patient groups and 13% in the control group. No significant differences in allele frequencies of any polymorphism were observed between the patient and control groups, although the B allele was more frequent in the patient groups (p=0.328.Conclusion: Our results provide no evidence of a relationship between MBL2 gene codon 54 polymorphism and the susceptibility to EM, SJS and SJS/TEN overlap syndrome. However, these findings should be confirmed in studies with a larger sample size.

  18. Dorfman-Chanarin syndrome: a rare neutral lipid storage disease.

    Science.gov (United States)

    Mitra, Souvik; Samanta, Moumita; Sarkar, Mihir; Chatterjee, Sukanta

    2010-01-01

    Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan's anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.

  19. Brittle Cornea Syndrome: Case Report with Novel Mutation in the PRDM5 Gene and Review of the Literature

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    Georgia Avgitidou

    2015-01-01

    Full Text Available A 3-year-old boy presented with acute corneal hydrops on the left eye and spontaneous corneal rupture on the right eye. A diagnosis of brittle cornea syndrome was confirmed by molecular analysis. A novel mutation, the homozygous variant c.17T>G, p.V6G, was found in the gene for PR-domain-containing protein 5 (PRDM5 in exon 1. Brittle cornea syndrome is a rare connective tissue disease with typical ocular, auditory, musculoskeletal, and cutaneous disorders. Almost all patients suffer from declined vision due to corneal scarring, thinning, and rupture. The most common ophthalmologic findings include keratoconus, progressive central corneal thinning, high myopia, irregular astigmatism, retinal detachment, and high risk for spontaneous corneal or scleral rupture. In addition to describing the case with a novel mutation here we review the current literature on brittle cornea syndrome pathogenesis, clinical findings, and therapy.

  20. What fans the fire: insights into mechanisms of leptin in metabolic syndrome-associated heart diseases.

    Science.gov (United States)

    Dong, Maolong; Ren, Jun

    2014-01-01

    Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

  1. Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.

    Science.gov (United States)

    Cortés-González, Vianney; Zenteno, Juan Carlos; Guzmán-Sánchez, Martín; Giordano-Herrera, Verónica; Guadarrama-Vallejo, Dalia; Ruíz-Quintero, Narlly; Villanueva-Mendoza, Cristina

    2016-12-01

    Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Genetic basis of prune belly syndrome: screening for HNF1β gene.

    Science.gov (United States)

    Granberg, Candace F; Harrison, Steven M; Dajusta, Daniel; Zhang, Shaohua; Hajarnis, Sachin; Igarashi, Peter; Baker, Linda A

    2012-01-01

    Although the cause of prune belly syndrome is unknown, familial evidence suggests a genetic component. Recently 2 nonfamilial cases of prune belly syndrome with chromosome 17q12 deletions encompassing the HNF1β gene have made this a candidate gene for prune belly syndrome. To date, there has been no large-scale screening of patients with prune belly syndrome for HNF1β mutations. We assessed the role of HNF1β in prune belly syndrome by screening for genomic mutations with functional characterization of any detected mutations. We studied patients with prune belly syndrome who were prospectively enrolled in our Pediatric Genitourinary DNA Repository since 2001. DNA from patient samples was amplified by polymerase chain reaction, sequenced for coding and splice regions of the HNF1β gene, and compared to control databases. We performed functional assay testing of the ability of mutant HNF1β to activate a luciferase construct with an HNF1β DNA binding site. From 32 prune belly syndrome probands (30 males, 2 females) HNF1β sequencing detected a missense mutation (V61G) in 1 child with prune belly syndrome. Absent in control databases, V61G was previously reported in 2 patients without prune belly syndrome who had congenital genitourinary anomalies. Functional testing showed similar luciferase activity compared to wild-type HNF1β, suggesting the V61G substitution does not disturb HNF1β function. One genomic HNF1β mutation was detected in 3% of patients with prune belly syndrome but found to be functionally normal. Thus, functionally significant HNF1β mutations are uncommon in prune belly syndrome, despite case reports of HNF1β deletions. Further genetic study is necessary, as identification of the genetic basis of prune belly syndrome may ultimately lead to prevention and improved treatments for this rare but severe syndrome. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Oncological implications of RET gene mutations in Hirschsprung's disease

    NARCIS (Netherlands)

    Sijmons, R. H.; Hofstra, R. M.; Wijburg, F. A.; Links, T. P.; Zwierstra, R. P.; Vermey, A.; Aronson, D. C.; Tan-Sindhunata, G.; Brouwers-Smalbraak, G. J.; maas, S. M.; Buys, C. H.

    1998-01-01

    Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be

  4. Oncological implications of RET gene mutations in Hirschsprung's disease

    NARCIS (Netherlands)

    Sijmons, RH; Hofstra, RMW; Wijburg, FA; Links, TP; Zwierstra, RP; Vermey, A; Aronson, DC; Tan-Sindhunata, G; Brouwers-Smalbraak, GJ; Maas, SM; Buys, CHCM

    1998-01-01

    Background-Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may

  5. Exon expression and alternatively spliced genes in Tourette Syndrome.

    Science.gov (United States)

    Tian, Yingfang; Liao, Isaac H; Zhan, Xinhua; Gunther, Joan R; Ander, Bradley P; Liu, Dazhi; Lit, Lisa; Jickling, Glen C; Corbett, Blythe A; Bos-Veneman, Netty G P; Hoekstra, Pieter J; Sharp, Frank R

    2011-01-01

    Tourette Syndrome (TS) is diagnosed based upon clinical criteria including motor and vocal tics. We hypothesized that differences in exon expression and splicing might be useful for pathophysiology and diagnosis. To demonstrate exon expression and alternatively spliced gene differences in blood of individuals with TS compared to healthy controls (HC), RNA was isolated from the blood of 26 un-medicated TS subjects and 23 HC. Each sample was run on Affymetrix Human Exon 1.0 ST (HuExon) arrays and on 3' biased U133 Plus 2.0 (HuU133) arrays. To investigate the differentially expressed exons and transcripts, analyses of covariance (ANCOVA) were performed, controlling for age, gender, and batch. Differential alternative splicing patterns between TS and HC were identified using analyses of variance (ANOVA) models in Partek. Three hundred and seventy-six exon probe sets were differentially expressed between TS and HC (raw P |1.2|) that separated TS and HC subjects using hierarchical clustering and Principal Components Analysis. The probe sets predicted TS compared to HC with a >90% sensitivity and specificity using a 10-fold cross-validation. Ninety genes (transcripts) had differential expression of a single exon (raw P < 0.005) and were predicted to be alternatively spliced (raw P < 0.05) in TS compared to HC. These preliminary findings might provide insight into the pathophysiology of TS and potentially provide prognostic and diagnostic biomarkers. However, the findings are tempered by the small sample size and multiple comparisons and require confirmation using PCR or deep RNA sequencing and a much larger patient population. Copyright © 2010 Wiley-Liss, Inc.

  6. Malignant Syndrome in a Patient with Parkinson's Disease

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    Nesrin Helvacı Yılmaz

    2012-09-01

    Full Text Available Malignant syndrome during the course of Parkinson’s disease usually occurs because of withdrawal or dose reduction of anti-Parkinsonian drugs, especially levodopa and may be fatal. Fever, rigidity, autonomic disfunction, elevated creatinin kinase level and confusion are the major clinical findings. We aimed to present a patient that was treated in our intensive care unit in order to emphasise the importance of correct diagnosis of this disease, to discuss the precipitating factors and to highlight the importance of early treatment

  7. Positional cloning of genes involved in the Beckwith-Wiedemann syndrome, hemihypertrophy, and associated childhood tumors

    NARCIS (Netherlands)

    Mannens, M.; Alders, M.; Redeker, B.; Bliek, J.; Steenman, M.; Wiesmeyer, C.; de Meulemeester, M.; Ryan, A.; Kalikin, L.; Voûte, T.; de Kraker, J.; Hoovers, J.; Slater, R.; Feinberg, A.; Little, P.; Westerveld, A.

    1996-01-01

    The Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that occurs with an incidence of 1:13,700 births. There is a striking incidence of childhood tumors found in BWS patients. Various lines of investigation have localized "imprinted" genes involved in BWS and associated

  8. Identification of a novel FBN1 gene mutation in a large Pakistani family with Marfan syndrome

    NARCIS (Netherlands)

    Micheal, S.; Khan, M.I.; Akhtar, F.; Weiss, M.M.; Islam, F.; Ali, M.; Qamar, R.; Maugeri, A.; Hollander, A.I. den

    2012-01-01

    PURPOSE: To describe a novel mutation in the fibrillin-1 (FBN1) gene in a large Pakistani family with autosomal dominant Marfan syndrome (MFS). METHODS: Blood samples were collected of 11 family members affected with Marfan syndrome, and DNA was isolated by phenol-extraction. The coding exons of

  9. Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects

    NARCIS (Netherlands)

    Weemaes, C.M.R.; van Tol, M.J.D.; Wang, J.; Dam, M.; van Eggermond, M.C.J.A.; Thijssen, P.E.; Aytekin, C.; Brunetti-Pierri, N.; van der Burg, M.; Graham Davies, E.; Ferster, A.; Furthner, D.; Gimelli, G.; Gennery, A.; Kloeckener-Gruissem, B.; Meyn, S.; Powell, C.; Reisli, I.; Schuetz, C.; Schulz, A.; Shugar, A.; van den Elsen, P.J.; van der Maarel, S.M.

    2013-01-01

    Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF

  10. Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects.

    NARCIS (Netherlands)

    Weemaes, C.M.R.; Tol, M.J. van; Wang, J; Ostaijen-ten Dam, M.M. van; Eggermond, M.C. van; Thijssen, P.E.; Aytekin, C.; Brunetti-Pierri, N.; Burg, M. van der; aham Davies, E. Gr; Ferster, A.; Furthner, D.; Gimelli, G.; Gennery, A.; Kloeckener-Gruissem, B.; Meyn, S.; Powell, C.; Reisli, I.; Schuetz, C.; Schulz, A.; Shugar, A.; Elsen, P.J. van den; Maarel, S.M. van der

    2013-01-01

    Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF

  11. Metabolic syndrome in inflammatory rheumatic diseases

    Directory of Open Access Journals (Sweden)

    G. La Montagna

    2011-09-01

    Full Text Available Toward the end of the last century a better knowledge of cardiovascular (CV risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called “metabolic” or “insulin resistance syndrome”. Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO and by The Third Report of The National Cholesterol Education Program’s Adult Treatment Panel (NCEP-ATP III. In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.

  12. Novel frameshift mutation in theKCNQ1gene responsible for Jervell and Lange-Nielsen syndrome.

    Science.gov (United States)

    Amirian, Azam; Dalili, Seyed Mohammad; Zafari, Zahra; Saber, Siamak; Karimipoor, Morteza; Akbari, Vahid; Fazelifar, Amir Farjam; Zeinali, Sirous

    2018-01-01

    Jervell and Lange-Nielsen syndrome is an autosomal recessive disorder caused by mutations in KCNQ1 or KCNE1 genes. The disease is characterized by sensorineural hearing loss and long QT syndrome. Here we present a 3.5-year-old female patient, an offspring of consanguineous marriage, who had a history of recurrent syncope and congenital sensorineural deafness. The patient and the family members were screened for mutations in KCNQ1 gene by linkage analysis and DNA sequencing. DNA sequencing showed a c.1532_1534delG (p. A512Pfs*81) mutation in the KCNQ1 gene in homozygous form. The results of short tandem repeat (STR) markers showed that the disease in the family is linked to the KCNQ1 gene. The mutation was confirmed in the parents in heterozygous form. This is the first report of this variant in KCNQ1 gene in an Iranian family. The data of this study could be used for early diagnosis of the condition in the family and genetic counseling.

  13. Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes

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    Podder Soumita

    2012-01-01

    Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.

  14. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  15. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.

    Science.gov (United States)

    Olson, Heather E; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E; Poduri, Annapurna

    2015-09-01

    Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. © 2015 Wiley Periodicals, Inc.

  16. Accurate Detection of Changes in Disease Activity in Primary Sjogren's Syndrome by the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index

    NARCIS (Netherlands)

    Seror, Raphaele; Mariette, Xavier; Bowman, Simon; Baron, Gabriel; Gottenberg, Jacques Eric; Boostma, Hendrika; Theander, Elke; Tzioufas, Athanasios; Vitali, Claudio; Ravaud, Philippe

    Objective. To assess and compare the sensitivity to change of the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) with that of other primary Sjogren's syndrome (SS) disease activity indexes. Methods. We abstracted 96 patient profiles, including data on 3

  17. THE ROLE OF GENE IN CARDIOVASCULAR DISEASES

    OpenAIRE

    Rafiya Begum1 , Syeda Zeba Hyder Zaidi2 , Nuha Rasheed3 and Abdul Saleem Mohammad 4

    2017-01-01

    Interleukin (IL)-18 plays a key role in atherosclerosis and its complications. Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. Cardiovascular disease includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, heart arrhythmia, congenital heart disease, valvular heart disease, cardit...

  18. Coral disease physiology: the impact of Acroporid white syndrome on Symbiodinium

    DEFF Research Database (Denmark)

    Roff, G.; Kvennefors, E. C. E.; Ulstrup, Karin Elizabeth

    2008-01-01

    Acroporid white syndrome, a disease-like syndrome from the Great Barrier Reef, results from degenerative host tissue at lesion borders. Tissue preceding lesion borders appears visually healthy, but it is currently unclear whether the endosymbiotic zooxanthellae (Symbiodinium) are physiologically ...

  19. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology.

    Science.gov (United States)

    Spataro, Nino; Rodríguez, Juan Antonio; Navarro, Arcadi; Bosch, Elena

    2017-02-01

    Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease. © The Author 2017. Published by Oxford University Press.

  20. Truncating mutation in the NHS gene: phenotypic heterogeneity of Nance-Horan syndrome in an asian Indian family.

    Science.gov (United States)

    Ramprasad, Vedam Lakshmi; Thool, Alka; Murugan, Sakthivel; Nancarrow, Derek; Vyas, Prateep; Rao, Srinivas Kamalakar; Vidhya, Authiappan; Ravishankar, Krishnamoorthy; Kumaramanickavel, Govindasamy

    2005-01-01

    A four-generation family containing eight affected males who inherited X-linked developmental lens opacity and microcornea was studied. Some members in the family had mild to moderate nonocular clinical features suggestive of Nance-Horan syndrome. The purpose of the study was to map genetically the gene in the large 57-live-member Asian-Indian pedigree. PCR-based genotyping was performed on the X-chromosome, by using fluorescent microsatellite markers (10-cM intervals). Parametric linkage analysis was performed by using two disease models, assuming either recessive or dominant X-linked transmission by the MLINK/ILINK and FASTLINK (version 4.1P) programs (http:www.hgmp.mrc.ac.uk/; provided in the public domain by the Human Genome Mapping Project Resources Centre, Cambridge, UK). The NHS gene at the linked region was screened for mutation. By fine mapping, the disease gene was localized to Xp22.13. Multipoint analysis placed the peak LOD of 4.46 at DSX987. The NHS gene mapped to this region. Mutational screening in all the affected males and carrier females (heterozygous form) revealed a truncating mutation 115C-->T in exon 1, resulting in conversion of glutamine to stop codon (Q39X), but was not observed in unaffected individuals and control subjects. conclusions. A family with X-linked Nance-Horan syndrome had severe ocular, but mild to moderate nonocular, features. The clinical phenotype of the truncating mutation (Q39X) in the NHS gene suggests allelic heterogeneity at the NHS locus or the presence of modifier genes. X-linked families with cataract should be carefully examined for both ocular and nonocular features, to exclude Nance-Horan syndrome. RT-PCR analysis did not suggest nonsense-mediated mRNA decay as the possible mechanism for clinical heterogeneity.

  1. [Association between angiotensin-converting enzyme 2 gene polymorphisms and childhood primary nephrotic syndrome].

    Science.gov (United States)

    Qiu, Ming-Yu; Xie, Qin-Fang; Wang, Li-Na; Yu, Li

    2015-03-01

    Angiotensin-converting enzyme 2 (ACE2) gene polymorphisms have been shown to be implicated in hypertension, diabetic nephropathy, and other diseases. However, it remains unclear whether ACE2 gene polymorphisms are involved in the development of primary nephrotic syndrome (PNS) in children. The aim of this study was to assess the association between A9570G polymorphisms of ACE2 gene and PNS in a group of Han children in Guangdong Province, China. The genotype distribution and allele frequency of ACE2 gene A9570G in 66 children with PNS and 60 healthy subjects (control group) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Allele frequency and genotype distribution showed no significant difference between the PNS and control groups whether in female or in male children (P>0.05). The PNS group was classified into the glucocorticoid-sensitive and glucocorticoid-resistant subgroups according to glucocorticoid treatment response. Subgroup analysis revealed that in female children, the frequency of GG genotype was 17% in the glucocorticoid-sensitive group vs 45% in the glucocorticoid-sensitive group (P=0.018); the frequency of G allele was 31% in the glucocorticoid-sensitive group vs 61% in the glucocorticoid-resistant group (P=0.023). In male children, the frequency of G genotype/G allele was 36% in the glucocorticoid-sensitive group vs 64% in the glucocorticoid-resistant group (P=0.017). There is no clear association between ACE2 gene A9570G polymorphisms and childhood PNS, but ACE2 gene A9570G polymorphisms might be associated with glucocorticoid treatment response in children with PNS. The G allele might be a genetic susceptibility factor of glucocorticoid resistance in children with PNS.

  2. Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

    Science.gov (United States)

    Trolle, Christian; Mortensen, Kristian H; Pedersen, Lisbeth N; Berglund, Agnethe; Jensen, Henrik K; Andersen, Niels H; Gravholt, Claus H

    2013-01-01

    QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett's (bQTc) and Hodges's formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (pTurner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

  3. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

    Science.gov (United States)

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  4. PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome.

    Science.gov (United States)

    Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; Del Sol, A

    2011-08-11

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network, the state of which can be shifted from the healthy to a stable diseased state. We found that a group of differentially expressed genes are involved in bi-stable switches and form a core network, the state of which changes with disease progression. These findings support the idea that bi-stable switches may be a mechanism for locking the core gene network into a diseased state and for efficiently propagating perturbations to more distant regions of the network. A structural analysis of the PPARγ-RXRα dimer complex supports the hypothesis of a major structural change between the two states, and this may represent an important mechanism leading to the differential expression observed in the core network.

  5. Milk alkali syndrome in an infant with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Kari JA

    2012-06-01

    Full Text Available Jameela A Kari, Sherif M El DesokyDepartment of Pediatrics and Pediatric Nephrology Unit, King Abdulaziz University, Jeddah, Kingdom of Saudi ArabiaAbstract: We report a case of milk alkali syndrome in a 15-month-old infant who had chronic kidney disease. His kidney function worsened, with creatinine raised from 1.11 mg/dL (98 µmol/L to 3.98 mg/dL (350.3 µmol/L, normal 0.4–1.0 mg/dL (35–91 µmol. He had hypercalcemia, serum calcium level 3.11 (normal 2.1–2.6 mmol/L, and metabolic alkalosis, HCO3 48.7 (normal 21–26 mmol/L. His kidney function returned to its base level and his calcium and bicarbonate levels normalized with adjustment of calcium carbonate and sodium bicarbonate doses. We report this case to highlight an unusual complication and to review the literature on milk alkali syndrome which is rare in children.Keywords: milk alkali syndrome, infants, chronic kidney disease

  6. Down syndrome and Alzheimer's disease: Common pathways, common goals.

    Science.gov (United States)

    Hartley, Dean; Blumenthal, Thomas; Carrillo, Maria; DiPaolo, Gilbert; Esralew, Lucille; Gardiner, Katheleen; Granholm, Ann-Charlotte; Iqbal, Khalid; Krams, Michael; Lemere, Cynthia; Lott, Ira; Mobley, William; Ness, Seth; Nixon, Ralph; Potter, Huntington; Reeves, Roger; Sabbagh, Marwan; Silverman, Wayne; Tycko, Benjamin; Whitten, Michelle; Wisniewski, Thomas

    2015-06-01

    In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  7. Analysis of unstable DNA sequence in FRM1 gene in Polish families with fragile X syndrome

    International Nuclear Information System (INIS)

    Milewski, Michal; Bal, Jerzy; Obersztyn, Ewa; Bocian, Ewa; Mazurczak, Tadeusz; Zygulska, Marta; Horst, Juergen; Deelen, Wout H.; Halley, Dicky J.J.

    1996-01-01

    The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGC repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted. (author). 19 refs., 4 figs, 1 tab

  8. Rare disease relations through common genes and protein interactions.

    Science.gov (United States)

    Fernandez-Novo, Sara; Pazos, Florencio; Chagoyen, Monica

    2016-06-01

    ODCs (Orphan Disease Connections), available at http://csbg.cnb.csic.es/odcs, is a novel resource to explore potential molecular relations between rare diseases. These molecular relations have been established through the integration of disease susceptibility genes and human protein-protein interactions. The database currently contains 54,941 relations between 3032 diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Disease candidate gene identification and prioritization using protein interaction networks

    Directory of Open Access Journals (Sweden)

    Aronow Bruce J

    2009-02-01

    Full Text Available Abstract Background Although most of the current disease candidate gene identification and prioritization methods depend on functional annotations, the coverage of the gene functional annotations is a limiting factor. In the current study, we describe a candidate gene prioritization method that is entirely based on protein-protein interaction network (PPIN analyses. Results For the first time, extended versions of the PageRank and HITS algorithms, and the K-Step Markov method are applied to prioritize disease candidate genes in a training-test schema. Using a list of known disease-related genes from our earlier study as a training set ("seeds", and the rest of the known genes as a test list, we perform large-scale cross validation to rank the candidate genes and also evaluate and compare the performance of our approach. Under appropriate settings – for example, a back probability of 0.3 for PageRank with Priors and HITS with Priors, and step size 6 for K-Step Markov method – the three methods achieved a comparable AUC value, suggesting a similar performance. Conclusion Even though network-based methods are generally not as effective as integrated functional annotation-based methods for disease candidate gene prioritization, in a one-to-one comparison, PPIN-based candidate gene prioritization performs better than all other gene features or annotations. Additionally, we demonstrate that methods used for studying both social and Web networks can be successfully used for disease candidate gene prioritization.

  10. Neonatal Marfan syndrome caused by an exon 25 mutation of the fibrillin-1 gene.

    Science.gov (United States)

    Elçioglu, N H; Akalin, F; Elçioglu, M; Comeglio, P; Child, A H

    2004-01-01

    Neonatal Marfan syndrome caused by an exon 25 mutation of the Fibrillin-1 gene: We describe a male infant with severe arachnodactyly, hypermobility of the fingers, flexion contractures of elbows, wrists, hips, and knees, microretrognathia, crumpled ears, rockerbottom feet, loose redundant skin, and lens dislocations. Cardiac valve insufficiency and aortic dilatation resulted in cardiac failure, decompensated with digitalisation and death occurred at the age of 4 months. This case represents the severe end of the clinical spectrum of Marfan syndrome, namely neonatal Marfan syndrome. Molecular diagnostic analyses confirmed a de novo exon 25 mutation in the FBN1 gene.

  11. Nonalcoholic fatty liver disease and polycystic ovary syndrome

    Science.gov (United States)

    Vassilatou, Evangeline

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594

  12. Severe visual impairment and retinal changes in a boy with a deletion of the gene for Nance-Horan syndrome.

    Science.gov (United States)

    Mathys, R; Deconinck, H; Keymolen, K; Jansen, A; Van Esch, H

    2007-01-01

    We present the ophthalmologic findings in a boy with a deletion of Xp22 comprising the gene for Nance-Horan syndrome. Different mechanisms underlying the visual impairment in Nance-Horan syndrome are discussed.

  13. Clinical characteristics and STK11 gene mutations in Chinese children with Peutz-Jeghers syndrome.

    Science.gov (United States)

    Huang, Zhiheng; Miao, Shijian; Wang, Lin; Zhang, Ping; Wu, Bingbing; Wu, Jie; Huang, Ying

    2015-11-25

    Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by gastrointestinal hamartomatous polyps and mucocutaneous melanin spots. Germline mutation of the serine/threonine kinase 11 (STK11) gene are responsible for PJS. In this study, we investigated the clinical characteristics and molecular basis of the disease in Chinese children with PJS. Thirteen children diagnosed with PJS in our hospital were enrolled in this study from 2011 to 2015, and their clinical data on polyp characteristics, intussusceptions events, family histories, etc. were described. Genomic DNA was extracted from whole-blood samples from each subject, and the entire coding sequence of the STK11 gene was amplified by polymerase chain reaction and analyzed by direct sequencing. The median age at the onset of symptoms was 2 years and 4 months. To date, these children have undergone 40 endoscopy screenings, 17 laparotomies and 9 intussusceptions. Polyps were found in the stomach, duodenum, small bowel, colon and rectum, with large polyps found in 7 children. Mutations were found in eleven children, including seven novel mutations (c.481het_dupA, c.943_944het_delCCinsG, c.397het_delG, c.862 + 1G > G/A, c.348_349het_delGT, and c.803_804het_delGGinsC and c.121_139de l19insTT) and four previously reported mutations (c.658C > C/T, c.890G > G/A, c.1062 C > C/G, and c.290 + 1G > G/A). One PJS patient did not have any STK11 mutations. The polyps caused significant clinical consequences in children with PJS, and mutations of the STK11 gene are generally the cause of PJS in Chinese children. This study expands the spectrum of known STK11 gene mutations.

  14. Gene therapy: Regulations, ethics and its practicalities in liver disease

    OpenAIRE

    Jin, Xi; Yang, Yi-Da; Li, You-Ming

    2008-01-01

    Gene therapy is a new and promising approach which opens a new door to the treatment of human diseases. By direct transfer of genetic materials to the target cells, it could exert functions on the level of genes and molecules. It is hoped to be widely used in the treatment of liver disease, especially hepatic tumors by using different vectors encoding the aim gene for anti-tumor activity by activating primary and adaptive immunity, inhibiting oncogene and angiogenesis. Despite the huge curati...

  15. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.

    Science.gov (United States)

    Bierzynska, Agnieszka; McCarthy, Hugh J; Soderquest, Katrina; Sen, Ethan S; Colby, Elizabeth; Ding, Wen Y; Nabhan, Marwa M; Kerecuk, Larissa; Hegde, Shivram; Hughes, David; Marks, Stephen; Feather, Sally; Jones, Caroline; Webb, Nicholas J A; Ognjanovic, Milos; Christian, Martin; Gilbert, Rodney D; Sinha, Manish D; Lord, Graham M; Simpson, Michael; Koziell, Ania B; Welsh, Gavin I; Saleem, Moin A

    2017-04-01

    Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis. Pediatric patients with SRNS were identified via a national United Kingdom Renal Registry. Whole exome sequencing was performed on 187 patients, of which 12% have a positive family history with a focus on the 53 genes currently known to be associated with nephrotic syndrome. Genetic findings were correlated with individual case disease characteristics. Disease causing variants were detected in 26.2% of patients. Most often this occurred in the three most common SRNS-associated genes: NPHS1, NPHS2, and WT1 but also in 14 other genes. The genotype did not always correlate with expected phenotype since mutations in OCRL, COL4A3, and DGKE associated with specific syndromes were detected in patients with isolated renal disease. Analysis by primary/presumed compared with secondary steroid resistance found 30.8% monogenic disease in primary compared with none in secondary SRNS permitting further mechanistic stratification. Genetic SRNS progressed faster to end stage renal failure, with no documented disease recurrence post-transplantation within this cohort. Primary steroid resistance in which no gene mutation was identified had a 47.8% risk of recurrence. In this unbiased pediatric population, whole exome sequencing allowed screening of all current candidate genes. Thus, deep phenotyping combined with whole exome sequencing is an effective tool for early identification of SRNS etiology, yielding an evidence-based algorithm for clinical management. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  16. Birt-Hogg-Dube Syndrome with a Novel Mutation in the FLCN Gene.

    Science.gov (United States)

    Kayhan, Gulsum; Yılmaz Demirci, Nilgun; Turktas, Haluk; Ergun, Mehmet Ali

    2017-10-01

    Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant disease characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax; its cause is a heterozygous mutation in the FLCN gene. Colorectal polyps and carcinoma have also been reported in BHDS. FLCN mutations can be detected in patients with isolated primary spontaneous pneumothorax (PSP), so PSP may present as part of BHDS. The aim of this report is to enhance awareness that patients presenting with spontaneous PSP should be evaluated for FLCN mutations. A 44-year-old woman with PSP and her parents were analyzed for FLCN mutations. One of the patient's paternal aunts had a PSP and two of her paternal aunts had colon cancer diagnosed at early ages. A novel in-frame deletion in the FLCN gene, c.932_933delCT (P311Rfs*78), was detected in the proband and in her unaffected father. We recommend that molecular analysis of the FLCN gene be performed in patients with PSP and their families, and that mutation carriers be examined for kidney and colon tumors.

  17. Interferons in Sjögren’s syndrome: genes, mechanisms, and effects

    Directory of Open Access Journals (Sweden)

    He eLi

    2013-09-01

    Full Text Available Sjögren’s syndrome (SS is a common, progressive autoimmune exocrinopathy distinguished by dry eyes and mouth and affects ~0.7% of European population. Overexpression of transcripts induced by interferons (IFN, termed as an ‘IFN signature’, has been found in SS patients. Four microarray studies have been published in SS that identified dysregulated genes within type I IFN signaling in either salivary glands or peripheral blood of SS patients. The mechanism of this type I IFN activation is still obscure, but several possible explanations have been proposed, including virus infection-initiated and immune-complex-initiated type I IFN production by plasmacytoid dendritic cells (pDCs. Genetic predisposition to increased type I IFN signaling is supported by candidate gene studies showing evidence for association of variants within IFN-related genes. Once activated, IFN signaling may contribute to numerous aspects of SS pathophysiology, including lymphocyte infiltration into exocrine glands, autoantibody production, and glandular cell apoptosis. Thus, dysregulation of IFN pathways is an important feature that can be potentially used as a serum biomarker for diagnosis and targeting of new treatments in this complex autoimmune disease.

  18. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

    Science.gov (United States)

    van der Crabben, Saskia N.; Hennus, Marije P.; McGregor, Grant A.; Ritter, Deborah I.; Nagamani, Sandesh C.S.; Wells, Owen S.; Harakalova, Magdalena; Chinn, Ivan K.; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M.; Terheggen-Lagro, Suzanne W.; van Lieshout, Stef; van Roosmalen, Markus J.; Renkens, Ivo; Duran, Karen; Nijman, Isaac J.; Kloosterman, Wigard P.; Hennekam, Eric; van Hasselt, Peter M.; Wheeler, David A.; Palecek, Jan J.; Lehmann, Alan R.; Oliver, Antony W.; Pearl, Laurence H.; Plon, Sharon E.; Murray, Johanne M.

    2016-01-01

    The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

  19. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Directory of Open Access Journals (Sweden)

    Junyu Zhang

    Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  20. Syndromic Hirschsprung's disease and associated congenital heart disease: a systematic review.

    Science.gov (United States)

    Duess, Johannes W; Puri, Prem

    2015-08-01

    Hirschsprung's disease (HD) occurs as an isolated phenotype in 70% of infants and is associated with additional congenital anomalies or syndromes in approximately 30% of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5-8% of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. A systematic review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "congenital megacolon", "congenital heart disease" and "congenital heart defect" was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3%. In infants with syndromic disorders, the overall prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51%). Septation defects were recorded in 57% (atrial septal defects in 29%, ventricular septal defects in 32%), a patent ductus arteriosus in 39%, vascular abnormalities in 16%, valvular heart defects in 4% and Tetralogy of Fallot in 7%. The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities.

  1. Kawasaki disease shock syndrome: a rare and severe complication of Kawasaki disease.

    Science.gov (United States)

    Çakan, Mustafa; Gemici, Hakan; Aktay-Ayaz, Nuray; Keskindemirci, Gonca; Bornaun, Helen; İkizoğlu, Tarkan; Çeliker, Alpay

    2016-01-01

    Kawasaki disease is an acute systemic vasculitis that occurs most commonly in young children. It affects medium-sized muscular arteries and the coronary arteries are the predominant site of involvement. Morbidity and mortality is generally due to coronary artery aneurysms that develop during the chronic phase. Although it is well known that Kawasaki disease can cause myocarditis, tachycardia and heart failure during acute stage, Kawasaki disease shock syndrome has been recently described. It is characterized by hypotension, signs and symptoms of poor perfusion and a shock-like state. Herein we describe two cases of Kawasaki disease shock syndrome that were treated in the pediatric intensive care unit and followed a course without morbidity or mortality.

  2. The SAPHO syndrome: defining the radiologic spectrum of diseases comprising the syndrome

    International Nuclear Information System (INIS)

    Sugimoto, H.; Tamura, K.; Fujii, T.

    1998-01-01

    The objective of our study was to clarify the radiologic spectrum of disease entities belonging to the SAPHO syndrome (SAPHO being an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis). A retrospective analysis of radiologic data was undertaken to determine the relationship of the osteoarthritic changes seen in palmoplantar pustulosis (PPP, n = 179), acne (n = 3), psoriasis vulgaris (PsV, n = 355), generalized pustular psoriasis (GPP, n = 25), and chronic recurrent multifocal osteomyelitis (CRMO, n = 4). Osseous changes of PPP, acne, and CRMO overlap each other; 7 PPP, 2 acne, and 3 CRMO patients manifested stenocostoclavicular hyperostosis as well as hyperostosis of the spine, pelvis, and/or femur. These findings were not seen in either PsV or GPP patients. Thirteen PsV and 4 GPP patients had peripheral arthritis and/or symmetrical sacroiliitis, which were not observed in the PPP, acne, and CRMO patients. The PPP, acne, and CRMO patients may be grouped as belonging to the single disease entity, namely SAPHO syndrome. Our findings do not support the inclusion of PsV and GPP in the spectrum of this syndrome. (orig.)

  3. The SAPHO syndrome: defining the radiologic spectrum of diseases comprising the syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, H.; Tamura, K. [Department of Radiology, Jichi Medical School, 3311 Minamikawachi-machi, Kawachi-gun, Tochigi-ken, 329-04 (Japan); Fujii, T. [Department of Pathology, Jichi Medical School, 3311 Minamikawachi-machi, Kawachi-gun, Tochigi-ken, 329-04 (Japan)

    1998-06-02

    The objective of our study was to clarify the radiologic spectrum of disease entities belonging to the SAPHO syndrome (SAPHO being an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis). A retrospective analysis of radiologic data was undertaken to determine the relationship of the osteoarthritic changes seen in palmoplantar pustulosis (PPP, n = 179), acne (n = 3), psoriasis vulgaris (PsV, n = 355), generalized pustular psoriasis (GPP, n = 25), and chronic recurrent multifocal osteomyelitis (CRMO, n = 4). Osseous changes of PPP, acne, and CRMO overlap each other; 7 PPP, 2 acne, and 3 CRMO patients manifested stenocostoclavicular hyperostosis as well as hyperostosis of the spine, pelvis, and/or femur. These findings were not seen in either PsV or GPP patients. Thirteen PsV and 4 GPP patients had peripheral arthritis and/or symmetrical sacroiliitis, which were not observed in the PPP, acne, and CRMO patients. The PPP, acne, and CRMO patients may be grouped as belonging to the single disease entity, namely SAPHO syndrome. Our findings do not support the inclusion of PsV and GPP in the spectrum of this syndrome. (orig.) With 7 figs., 2 tabs., 30 refs.

  4. Identification of a novel de novo mutation in the NIPBL gene in an Iranian patient with Cornelia de Lange syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Mohamadian Gholamreza

    2011-06-01

    Full Text Available Abstract Background Cornelia de Lange syndrome is characterized by dysmorphic facial features, hirsutism, severe growth and developmental delay. Germline mutations in the NIPBL gene with an autosomal dominant pattern and in the SMC1A gene with an X-linked pattern have been identified in Cornelia de Lange syndrome. Case presentation A two-month-old Iranian boy who showed multiple congenital anomalies was referred to the genetic center of a welfare organization in southwest Iran. He was the second child of a non-consanguineous marriage, born after full term with normal delivery. His birth weight was 3110 g, his length was 46 cm and his head circumference was 30 cm. Both parents were clinically asymptomatic, with no positive history of any deformity in their respective families. Conclusions Sequencing of the NIPBL gene from our patient revealed a single-base deletion of thymidine in exon 10 (c.516delT. This mutation presumably results in premature termination at codon 526. We did not observe this mutation in the parents of our patient with Cornelia de Lange syndrome. The results presented here enlarge the spectrum of NIPBL gene mutations associated with Cornelia de Lange syndrome by identifying a novel de novo mutation in an Iranian patient with Cornelia de Lange syndrome and further support the hypothesis that NIPBL mutations are disease-causing mutations leading to Cornelia de Lange syndrome.

  5. Identification of a novel de novo mutation in the NIPBL gene in an Iranian patient with Cornelia de Lange syndrome: A case report.

    Science.gov (United States)

    Galehdari, Hamid; Monajemzadeh, Roya; Nazem, Habibolah; Mohamadian, Gholamreza; Pedram, Mohammad

    2011-06-27

    Cornelia de Lange syndrome is characterized by dysmorphic facial features, hirsutism, severe growth and developmental delay. Germline mutations in the NIPBL gene with an autosomal dominant pattern and in the SMC1A gene with an X-linked pattern have been identified in Cornelia de Lange syndrome. A two-month-old Iranian boy who showed multiple congenital anomalies was referred to the genetic center of a welfare organization in southwest Iran. He was the second child of a non-consanguineous marriage, born after full term with normal delivery. His birth weight was 3110 g, his length was 46 cm and his head circumference was 30 cm. Both parents were clinically asymptomatic, with no positive history of any deformity in their respective families. Sequencing of the NIPBL gene from our patient revealed a single-base deletion of thymidine in exon 10 (c.516delT). This mutation presumably results in premature termination at codon 526. We did not observe this mutation in the parents of our patient with Cornelia de Lange syndrome. The results presented here enlarge the spectrum of NIPBL gene mutations associated with Cornelia de Lange syndrome by identifying a novel de novo mutation in an Iranian patient with Cornelia de Lange syndrome and further support the hypothesis that NIPBL mutations are disease-causing mutations leading to Cornelia de Lange syndrome.

  6. Clinical association: Lyme disease and Guillain-Barre syndrome.

    Science.gov (United States)

    Patel, Kinner; Shah, Siddharth; Subedi, Dinesh

    2017-10-01

    Guillain-Barre Syndrome (GBS) is a life-threatening condition in which patients may present to the Emergency Department in respiratory distress leading to death. The early identification and treatment of such a condition is paramount in preventing mortality. While there are many infections associated with GBS, the association with Lyme disease is uncommon. Through our case we aim to highlight Borrelia burgdorferi as an important antecedent infection associated with the development of GBS. In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Neuroretinitis: a clinical syndrome of cat-scratch disease.

    Science.gov (United States)

    Rost Monahan S

    2000-12-01

    Cat-scratch disease is usually a benign self-limited illness, characterized by regional lymphadenopathy lasting between 3 and 6 weeks. The causative organism is Bartonella henselae, a small gram-negative rod. Between 1 and 2% of patients who contract the illness experience blurred vision, metamorphopsia and scotomas as a result of neuroretinitis, an associated clinical syndrome. The classical clinical findings in cat-scratch neuroretinitis include disc edema and a stellate pattern of exudates in the macula. However, a myriad of other signs has been documented, suggesting a much wider spectrum of intra-ocular disease. The following case report presents a young patient with neuroretinitis, and a history of lymphadenopathy secondary to cat-scratch disease.

  8. Metabolic syndrome, chronic kidney, and cardiovascular diseases: role of adipokines.

    Science.gov (United States)

    Tesauro, Manfredi; Canale, Maria Paola; Rodia, Giuseppe; Di Daniele, Nicola; Lauro, Davide; Scuteri, Angelo; Cardillo, Carmine

    2011-03-07

    Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS) leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD). Albuminuria is a major risk factor for cardiovascular diseases (CVDs). Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

  9. Metabolic Syndrome, Chronic Kidney, and Cardiovascular Diseases: Role of Adipokines

    Directory of Open Access Journals (Sweden)

    Manfredi Tesauro

    2011-01-01

    Full Text Available Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD. Albuminuria is a major risk factor for cardiovascular diseases (CVDs. Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

  10. Phenotype of asthma-chronic obstructive pulmonary disease overlap syndrome.

    Science.gov (United States)

    Rhee, Chin Kook

    2015-07-01

    Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases. By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS). However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype. Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS. Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis. Medical treatment for ACOS should be tailored according to phenotype. A narrower definition of ACOS that includes both spirometric and clinical criteria is needed.

  11. [Population frequency and age of mutation G5741→A in gene NBAS which is a cause of SOPH syndrome in Sakha (Yakutia) Republic].

    Science.gov (United States)

    Maksimova, N R; Nogovicina, A N; Kurtanov, Kh A; Alekseeva, E I

    2016-10-01

    SOPH syndrome (Short stature with Optic nerve atrophy and Pelger–Huët anomaly syndrome, OMIM#614800) is an autosomal recessive hereditary disease characterized by the following main clinical symptoms: postnatal hypoplasia, proportionately short stature, facial dysmorphism, micromelia of feet and hands, limp and loose skin, optic nerve atrophy, and Pelger–Huët anomaly of neutrophils. For the first time, this disease was described in Yakuts. The molecular-genetic study showed that its cause in Yakuts is mutation G5741→A in gene NBAS. On the basis of disequilibrium analysis for linkage of ten microsatellite markers flanking the NBAS gene with the disease, the haplotype of the founder chromosome was determined. The age of the mutation in Yakutia was estimated to be about 804 ± 140 years. The frequency of heterozygous carriers of mutation G5741→A (R1914H) in gene NBAS was found, which averaged 13 per 1000 healthy Yakuts.

  12. Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

    Science.gov (United States)

    Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

    2018-02-01

    Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

  13. Diagnostic indicators for blood stasis syndrome patients with gynaecological diseases.

    Science.gov (United States)

    Jung, Jeeyoun; Ko, Mi Mi; Lee, Myeong Soo; Lee, So Min; Lee, Ju Ah

    2017-06-20

    To investigate the important diagnostic indicators for blood stasis syndrome (BSS) in patients of childbearing age with gynaecological diseases. A partial least squared-discriminant analysis (PLS-DA) were applied to BSS symptoms data of patients with gynaecological diseases, and the diagnostic indicators used by doctors of Korean medicine (DKMs) among BSS patients with gynaecological diseases were also investigated. A total of 103 patients of childbearing age with gynaecological diseases and 40 healthy controls were enrolled. Among the 103 patients, 63 (61.7%) and 40 (38.8%) were diagnosed with BSS and non-BSS, respectively, and BSS patients exhibited a more severe extent of disease. A score plot of PLS-DA showed clearly different patterns among the 3 groups. Based on the variable importance on projection of PLS-DA model, menstrual pains, dark lumps in the menstrual blood, ileocoecal tenderness and resistance, sharp pains, and sublingual varicosities were selected as the top fifive most important indicators. Moreover, more than 75% of DKMs chose dark lumps in menstrual blood, menstrual pain, and dark menstrual blood as the diagnostic indicators of BSS in patients with gynaecological diseases, and more than 49% of them also considered sharp pains, dark red tongue, sublingual varicosities, and tendency to bruise easily as diagnostic indicators of BSS. DKMs focused on menstrual symptoms and certain gynaecological symptoms to diagnose BSS patients of childbearing age with female diseases.

  14. Heterozygous deletion at the SOX10 gene locus in two patients from a Chinese family with Waardenburg syndrome type II.

    Science.gov (United States)

    Wenzhi, He; Ruijin, Wen; Jieliang, Li; Xiaoyan, Ma; Haibo, Liu; Xiaoman, Wang; Jiajia, Xian; Shaoying, Li; Shuanglin, Li; Qing, Li

    2015-10-01

    Waardenburg syndrome (WS) is a rare disease characterized by sensorineural deafness and pigment disturbance. To date, almost 100 mutations have been reported, but few reports on cases with SOX10 gene deletion. The inheritance pattern of SOX10 gene deletion is still unclear. Our objective was to identify the genetic causes of Waardenburg syndrome type II in a two-generation Chinese family. Clinical evaluations were conducted in both of the patients. Microarray analysis and multiplex ligation-dependent probe amplification (MLPA) were performed to identify disease-related copy number variants (CNVs). DNA sequencing of the SOX10, MITF and SNAI2 genes was performed to identify the pathogenic mutation responsible for WS2. A 280kb heterozygous deletion at the 22q13.1 chromosome region (including SOX10) was detected in both of the patients. No mutation was found in the patients, unaffected family members and 30 unrelated healthy controls. This report is the first to describe SOX10 heterozygous deletions in Chinese WS2 patients. Our result conform the thesis that heterozygous deletions at SOX10 is an important pathogenicity for WS, and present as autosomal dominant inheritance. Nevertheless, heterozygous deletion of the SOX10 gene would be worth investigating to understand their functions and contributions to neurologic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Renin-angiotensin system gene expression and neurodegenerative diseases.

    Science.gov (United States)

    Goldstein, Benjamin; Speth, Robert C; Trivedi, Malav

    2016-07-01

    Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases. Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease. A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis. No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed. To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases. © The Author(s) 2016.

  16. Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report.

    Science.gov (United States)

    Dziedzic, Magdalena; Marjańska, Agata; Bąbol-Pokora, Katarzyna; Urbańczyk, Anna; Grześk, Elżbieta; Młynarski, Wojciech; Kołtan, Sylwia

    2017-07-27

    Pediatric autoinflammatory diseases are rare and still poorly understood conditions resulting from defective genetic control of innate immune system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2 protein, taking part in maintenance of immune homeostasis. Clinical form of resultant autoinflammatory condition depends on NOD2 genotype; usually patients with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory disease (NAID) or Crohn's disease. We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. Overlapping manifestations of two syndromes raised a significant diagnostic challenge, until next-generation molecular test (NGS) identified presence of three pathogenic variants of NOD2 gene: P268S, IVS8 +158 , 1007 fs, and established the ultimate diagnosis. Presence of multiple genetical abnormalities resulted in an ambiguous clinical presentation with overlapping symptoms of Blau syndrome and NAID. Final diagnosis of autoinflammatory disease opened new therapeutic possibilities, including the use of biological treatments.

  17. Collectrin gene screening in Turner syndrome patients with kidney ...

    Indian Academy of Sciences (India)

    common to all TS, generally results in the full syndrome phe- ... Keywords. Turner syndrome; collectrin; horseshoe kidney; human genetics. Journal of ..... J. M. and Alessandrini P. 2006 Multicystic dysplastic kidney with ipsilateral abnormalities of genitourinary tract, experience in children. Urology 67, 603–607. O'Brien J.

  18. Gene prioritization for livestock diseases by data integration

    DEFF Research Database (Denmark)

    Jiang, Li; Sørensen, Peter; Thomsen, Bo Stjerne

    2012-01-01

    in bovine mastitis. Gene-associated phenome profile and transcriptome profile in response to Escherichia coli infection in the mammary gland were integrated to make a global inference of bovine genes involved in mastitis. The top ranked genes were highly enriched for pathways and biological processes...... underlying inflammation and immune responses, which supports the validity of our approach for identifying genes that are relevant to animal health and disease. These gene-associated phenotypes were used for a local prioritization of candidate genes located in a QTL affecting the susceptibility to mastitis...

  19. Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

    Science.gov (United States)

    Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

    2009-09-01

    One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

  20. Decompression syndrome (Caisson disease in an Indian diver

    Directory of Open Access Journals (Sweden)

    Phatak Uday

    2010-01-01

    Full Text Available Acute decompression syndrome (Caisson′s disease is an acute neurological emergency in divers. It is caused due to release of nitrogen gas bubbles that impinge the blood vessels of the spinal cord and brain and result in severe neurodeficit. There are very few case reports in Indian literature. There are multiple factors in the pathogenesis of Acute decompression syndrome (Caisson′s disease such as health problems in divers (respiratory problems or congenital heart diseases like atrial septal defect, patent ductus arteriosus etc, speed of ascent from the depth and habits like smoking that render divers susceptible for such neurological emergency. Usually, immediate diagnosis of such a condition with MRI is not possible in hospitals in the Coastal border. Even though, MRI is performed, it has very low specificity and sensitivity. Facilities like hyperbaric oxygen treatment are virtually non-existent in these hospitals. Therefore, proper education of the divers and appropriate preventive measures in professional or recreational divers is recommended.

  1. Gut Microbiota in Health, Diverticular Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Diseases: Time for Microbial Marker of Gastrointestinal Disorders.

    Science.gov (United States)

    Lopetuso, Loris Riccardo; Petito, Valentina; Graziani, Cristina; Schiavoni, Elisa; Paroni Sterbini, Francesco; Poscia, Andrea; Gaetani, Eleonora; Franceschi, Francesco; Cammarota, Giovanni; Sanguinetti, Maurizio; Masucci, Luca; Scaldaferri, Franco; Gasbarrini, Antonio

    2018-01-01

    Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the "core dysbiosis" of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment. © 2017 S. Karger AG, Basel.

  2. Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene.

    Science.gov (United States)

    La Piana, Roberta; Vanasse, Michel; Brais, Bernard; Bernard, Genevieve

    2015-09-01

    Allan-Herndon-Dudley syndrome is an X-linked disease caused by mutations in the solute carrier family 16 member 2 (SLC16A2) gene. As SLC16A2 encodes the monocarboxylate transporter 8 (MCT8), a thyroid hormone transporter, patients with Allan-Herndon-Dudley syndrome present a specific altered thyroid hormone profile. Allan-Herndon-Dudley syndrome has been associated with myelination delay on the brain magnetic resonance imaging (MRI) of affected subjects. We report a patient with Allan-Herndon-Dudley syndrome characterized by developmental delay, hypotonia, and delayed myelination caused by a novel SLC16A2 mutation (p.L291R). The thyroid hormones profile in our patient was atypical for Allan-Herndon-Dudley syndrome. The follow-up examinations showed that the progression of the myelination was not accompanied by a clinical improvement. Our paper suggests that SLC16A2 mutations should be investigated in patients with myelination delay even when the thyroid function is not conclusively altered. © The Author(s) 2014.

  3. New mutations in the NHS gene in Nance-Horan Syndrome families from the Netherlands

    NARCIS (Netherlands)

    Florijn, Ralph J.; Loves, Willem; Maillette de Buy Wenniger-Prick, Liesbeth J. J. M.; Mannens, Marcel M. A. M.; Tijmes, Nel; Brooks, Simon P.; Hardcastle, Alison J.; Bergen, Arthur A. B.

    2006-01-01

    Mutations in the NHS gene cause Nance-Horan Syndrome (NHS), a rare X-chromosomal recessive disorder with variable features, including congenital cataract, microphthalmia, a peculiar form of the ear and dental anomalies. We investigated the NHS gene in four additional families with NHS from the

  4. A novel homozygous variant in the SMOC1 gene underlying Waardenburg anophthalmia syndrome.

    Science.gov (United States)

    Ullah, Asmat; Umair, Muhammad; Ahmad, Farooq; Muhammad, Dost; Basit, Sulman; Ahmad, Wasim

    2017-01-01

    Waardenburg anophthalmia syndrome (WAS), also known as ophthalmo-acromelic syndrome or anophthalmia-syndactyly, is a rare congenital disorder that segregates in an autosomal recessive pattern. Clinical features of the syndrome include malformation of the eyes and the skeleton. Mostly, WAS is caused by mutations in the SMOC-1 gene. The present report describes a large consanguineous family of Pakistani origin segregating Waardenburg anophthalmia syndrome in an autosomal recessive pattern. Genotyping followed by Sanger sequencing was performed to search for a candidate gene. SNP genotyping using AffymetrixGeneChip Human Mapping 250K Nsp array established a single homozygous region among affected members on chromosome 14q23.1-q24.3 harboring the SMOC1 gene. Sequencing of the gene revealed a novel homozygous missense mutation (c.812G>A; p.Cys271Tyr) in the family. This is the first report of Waardenburg anophthalmia syndrome caused by a SMOC1 variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SMOC-1 in causing WAS.

  5. Chronic graft versus host disease and nephrotic syndrome.

    Science.gov (United States)

    Barbouch, Samia; Gaied, Hanene; Abdelghani, Khaoula Ben; Goucha, Rim; Lakhal, Amel; Torjemen, Lamia; Hamida, Fethi Ben; Abderrahim, Ezzedine; Maiz, Hedi Ben; Adel, Khedher

    2014-09-01

    Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD). We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT). Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed membranous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

  6. Chronic graft versus host disease and nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Samia Barbouch

    2014-01-01

    Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

  7. A family with Townes-Brocks syndrome with congenital hypothyroidism and a novel mutation of the SALL1 gene.

    Science.gov (United States)

    Choi, Won Ik; Kim, Ji Hye; Yoo, Han Wook; Oh, Sung Hee

    2010-12-01

    Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital disorder caused by mutations in the SALL1 gene. Its signs and symptoms overlap with other genetic syndromes, including VACTERL association, Pendred syndrome, Baller-Gerold syndrome, and cat eye syndrome. Structural vertebral abnormalities, hypoplasia of the thumb, and radial bone abnormalities, which are not usually associated with TBS, help in the differential diagnosis of these syndromes. We report the case of a family whose members were diagnosed with TBS with congenital hypothyroidism and had a novel SALL1 gene mutation.

  8. Kennedy's disease and partial androgen insensitivity syndrome. Report of 4 cases and literature review.

    Science.gov (United States)

    Valera Yepes, Rocío; Virgili Casas, Maria; Povedano Panades, Monica; Guerrero Gual, Mireia; Villabona Artero, Carles

    2015-05-01

    Kennedy's disease, also known as bulbospinal muscular atrophy, is a rare, X-linked recessive neurodegenerative disorder affecting adult males. It is caused by expansion of an unstable cytosine-adenine-guanine tandem-repeat in exon 1 of the androgen-receptor gene on chromosome Xq11-12, and is characterized by spinal motor neuron progressive degeneration. Endocrinologically, these patients often have the features of hypogonadism associated to the androgen insensitivity syndrome, particularly its partial forms. We report 4 cases with the typical neurological presentation, consisting of slowly progressing generalized muscle weakness with atrophy and bulbar muscle involvement; these patients also had several endocrine manifestations; the most common non-neurological manifestation was gynecomastia. In all cases reported, molecular analysis showed an abnormal cytosine-adenine-guanine triplet repeat expansion in the androgen receptor gene. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  9. Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.

    Science.gov (United States)

    Maksimova, Nadezda; Hara, Kenju; Nikolaeva, Irina; Chun-Feng, Tan; Usui, Tomoaki; Takagi, Mineo; Nishihira, Yasushi; Miyashita, Akinori; Fujiwara, Hiroshi; Oyama, Tokuhide; Nogovicina, Anna; Sukhomyasova, Aitalina; Potapova, Svetlana; Kuwano, Ryozo; Takahashi, Hitoshi; Nishizawa, Masatoyo; Onodera, Osamu

    2010-08-01

    Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. To identify a causative gene for SOPH syndrome. Genomewide homozygosity mapping was conducted in 33 patients in 30 families. The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

  10. Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger–Huët anomaly

    Science.gov (United States)

    Maksimova, Nadezda; Hara, Kenju; Nikolaeva, Irina; Chun-Feng, Tan; Usui, Tomoaki; Takagi, Mineo; Nishihira, Yasushi; Miyashita, Akinori; Fujiwara, Hiroshi; Oyama, Tokuhide; Nogovicina, Anna; Sukhomyasova, Aitalina; Potapova, Svetlana; Kuwano, Ryozo; Takahashi, Hitoshi; Nishizawa, Masatoyo

    2010-01-01

    Background Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. Aims To identify a causative gene for SOPH syndrome. Methods Genomewide homozygosity mapping was conducted in 33 patients in 30 families. Results The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. Conclusion These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly. PMID:20577004

  11. (GPR98) gene in an Iranian family with Usher syndrome type II

    Indian Academy of Sciences (India)

    2014-12-04

    Dec 4, 2014 ... Usher syndrome (USH) is an autosomal recessive disease characterized by bilateral sensorineural ... Usher syndrome type 1 (USH1) which is manifested by severe to profound congenital ... down-sloping moderate sensorineural HL across all frequencies in this family. (c) Segregation of c.10019T>G (p.

  12. DiGeorge Syndrome: a not so rare disease

    Directory of Open Access Journals (Sweden)

    Angela BF Fomin

    2010-01-01

    Full Text Available INTRODUCTION: The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. OBJECTIVES: To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. METHODS: Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. RESULTS: Of 14 patients (8m - 18y11m, only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n = 12, facial abnormalities (n = 11, hypocalcemia (n = 5 and low lymphocyte count (n=2. CONCLUSION: The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia, and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up.

  13. Characterization of Burning Mouth Syndrome in Patients with Parkinson's Disease.

    Science.gov (United States)

    Bonenfant, David; Rompré, Pierre H; Rei, Nathalie; Jodoin, Nicolas; Soland, Valerie Lynn; Rey, Veronica; Brefel-Courbon, Christine; Ory-Magne, Fabienne; Rascol, Olivier; Blanchet, Pierre J

    2016-01-01

    To determine the prevalence and characteristics of burning mouth syndrome (BMS) in a Parkinson's disease (PD) population through a self-administered, custom-made survey. A total of 218 surveys were collected during regular outpatient visits at two Movement Disorders Clinics in Montreal (Canada) and Toulouse (France) to gather information about pain experience, PD-related symptoms, and oral and general health. A neurologist confirmed the diagnosis of PD, drug treatment, Hoehn-Yahr stage, and Schwab & England Activity of Daily Living score. Data between groups were compared using the independent samples Mann-Whitney U test and two-sided exact Fisher test. Data from 203 surveys were analyzed. BMS was reported by eight subjects (seven females and one male), resulting in a prevalence of 4.0% (95% confidence interval [CI] = 2.1-7.8). Five participants with chronic nonburning oral pain were excluded. PD severity and levodopa equivalent daily dose did not differ between non-BMS and BMS participants. Mean poor oral health index was higher in BMS compared to non-BMS subjects (49.0 vs 32.2 points, P < .05). BMS manifested after PD onset in seven patients, did not occur on a daily basis in four, and always coexisted with restless legs syndrome. This survey yielded a low prevalence of BMS in PD patients, indicating no strong link between the two conditions. An augmenting effect such as that resulting from drug treatment in restless legs syndrome or sensory neuropathy cannot be excluded.

  14. Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

    DEFF Research Database (Denmark)

    Bech, Sara; Petersen, Thor; Nørremølle, Anne

    2010-01-01

    with a Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats......-like phenotypes and ataxia syndromes, also in isolated cases....

  15. Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases.

    Science.gov (United States)

    Candotti, Fabio

    2014-04-01

    Gene transfer into the hematopoietic stem cell has shown curative potential for a variety of hematological disorders. Primary immunodeficiency diseases have led to the way in this field of gene therapy as an example and a model. Clinical results from the past 15 years have shown that significant improvement and even cure can be achieved for diseases such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease and Wiskott-Aldrich syndrome. Unfortunately, with the initial clear clinical benefits, the first serious complications of gene therapy have also occurred. In a significant number of patients treated using vectors based on murine gamma-retroviruses and carrying powerful viral enhancer elements, insertional oncogenesis events have resulted in acute leukemias that, in some cases, have had fatal outcomes. These serious adverse events have sparked a revision of the assessment of risks and benefits of integrating gene transfer for hematological diseases and prompted the development and application of new generations of viral vectors with recognized superior safety characteristics. This review summarizes the clinical experience of gene therapy for primary immunodeficiencies and discusses the likely avenues of progress in the future development of this expanding field of clinical investigations.

  16. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

    Directory of Open Access Journals (Sweden)

    José Ángel Cahua-Pablo

    2015-09-01

    Full Text Available Metabolic syndrome (MetS is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD. Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR = 2.9; p = 0.013 in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04. Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006. In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001. In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

  17. Inductive matrix completion for predicting gene-disease associations.

    Science.gov (United States)

    Natarajan, Nagarajan; Dhillon, Inderjit S

    2014-06-15

    Most existing methods for predicting causal disease genes rely on specific type of evidence, and are therefore limited in terms of applicability. More often than not, the type of evidence available for diseases varies-for example, we may know linked genes, keywords associated with the disease obtained by mining text, or co-occurrence of disease symptoms in patients. Similarly, the type of evidence available for genes varies-for example, specific microarray probes convey information only for certain sets of genes. In this article, we apply a novel matrix-completion method called Inductive Matrix Completion to the problem of predicting gene-disease associations; it combines multiple types of evidence (features) for diseases and genes to learn latent factors that explain the observed gene-disease associations. We construct features from different biological sources such as microarray expression data and disease-related textual data. A crucial advantage of the method is that it is inductive; it can be applied to diseases not seen at training time, unlike traditional matrix-completion approaches and network-based inference methods that are transductive. Comparison with state-of-the-art methods on diseases from the Online Mendelian Inheritance in Man (OMIM) database shows that the proposed approach is substantially better-it has close to one-in-four chance of recovering a true association in the top 100 predictions, compared to the recently proposed Catapult method (second best) that has bigdata.ices.utexas.edu/project/gene-disease. © The Author 2014. Published by Oxford University Press.

  18. Cell specificity dictates similarities in gene expression in multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Yuichiro Itoh

    Full Text Available Drug repurposing is an efficient approach in new treatment development since it leverages previous work from one disease to another. While multiple sclerosis (MS, Parkinson's disease (PD, and Alzheimer's disease (AD are all neurodegenerative diseases of the central nervous system (CNS and differ in many clinical and pathological aspects, it is possible that they may share some mechanistic features. We hypothesized that focusing on gene expression in a CNS cell type specific manner might uncover similarities between diseases that could be missed using whole tissue gene expression analyses. We found similarities and differences in gene expression in these three distinct diseases, depending upon cell type. Microglia genes were increased in all three diseases, and gene expression levels were correlated strongly among these three neurodegenerative diseases. In astrocytes and endothelia, upregulation and correlations were observed only between MS and PD, but not AD. Neuronal genes were down-regulated in all three diseases, but correlations of changes of individual genes between diseases were not strong. Oligodendrocyte showed gene expression changes that were not shared among the three diseases. Together these data suggest that treatments targeting microglia are most amenable to drug repurposing in MS, PD, and AD, while treatments targeting other CNS cells must be tailored to each disease.

  19. Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (APECED): A "Rare" Manifestation in a "Rare" Disease.

    Science.gov (United States)

    Fierabracci, Alessandra

    2016-07-12

    Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes) has been rarely reported in different series of patients and occurring more frequently in Finnish APECED patients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation of APECED in different populations highlighting the peculiar genetic and immunological features of the disease when occurring in the context of this syndrome.

  20. Sequential waves of gene expression in patients with clinically defined dengue illnesses reveal subtle disease phases and predict disease severity.

    Directory of Open Access Journals (Sweden)

    Peifang Sun

    Full Text Available BACKGROUND: Dengue virus (DENV infection can range in severity from mild dengue fever (DF to severe dengue hemorrhagic fever (DHF or dengue shock syndrome (DSS. Changes in host gene expression, temporally through the progression of DENV infection, especially during the early days, remains poorly characterized. Early diagnostic markers for DHF are also lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated host gene expression in a cohort of DENV-infected subjects clinically diagnosed as DF (n = 51 and DHF (n = 13 from Maracay, Venezuela. Blood specimens were collected daily from these subjects from enrollment to early defervescence and at one convalescent time-point. Using convalescent expression levels as baseline, two distinct groups of genes were identified: the "early" group, which included genes associated with innate immunity, type I interferon, cytokine-mediated signaling, chemotaxis, and complement activity peaked at day 0-1 and declined on day 3-4; the second "late" group, comprised of genes associated with cell cycle, emerged from day 4 and peaked at day 5-6. The up-regulation of innate immune response genes coincided with the down-regulation of genes associated with viral replication during day 0-3. Furthermore, DHF patients had lower expression of genes associated with antigen processing and presentation, MHC class II receptor, NK and T cell activities, compared to that of DF patients. These results suggested that the innate and adaptive immunity during the early days of the disease are vital in suppressing DENV replication and in affecting outcome of disease severity. Gene signatures of DHF were identified as early as day 1. CONCLUSIONS/SIGNIFICANCE: Our study reveals a broad and dynamic picture of host responses in DENV infected subjects. Host response to DENV infection can now be understood as two distinct phases with unique transcriptional markers. The DHF signatures identified during day 1-3 may have

  1. Identification of highly related references about gene-disease association.

    Science.gov (United States)

    Liu, Rey-Long; Shih, Chia-Chun

    2014-08-25

    Curation of gene-disease associations published in literature should be based on careful and frequent survey of the references that are highly related to specific gene-disease associations. Retrieval of the references is thus essential for timely and complete curation. We present a technique CRFref (Conclusive, Rich, and Focused References) that, given a gene-disease pair , ranks high those biomedical references that are likely to provide conclusive, rich, and focused results about g and d. Such references are expected to be highly related to the association between g and d. CRFref ranks candidate references based on their scores. To estimate the score of a reference r, CRFref estimates and integrates three measures: degree of conclusiveness, degree of richness, and degree of focus of r with respect to . To evaluate CRFref, experiments are conducted on over one hundred thousand references for over one thousand gene-disease pairs. Experimental results show that CRFref performs significantly better than several typical types of baselines in ranking high those references that expert curators select to develop the summaries for specific gene-disease associations. CRFref is a good technique to rank high those references that are highly related to specific gene-disease associations. It can be incorporated into existing search engines to prioritize biomedical references for curators and researchers, as well as those text mining systems that aim at the study of gene-disease associations.

  2. Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

    Directory of Open Access Journals (Sweden)

    Christian Trolle

    Full Text Available QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc over time and relate the findings to the Turner syndrome phenotype.Adult women with Turner syndrome (n = 88 were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%, and adjusted for influence of heart rate by Bazett's (bQTc and Hodges's formula (hQTc. The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms. Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done.The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms compared to controls (390.4 ± 17.8 ms was prolonged (p432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2 and one in a minor Long QT syndrome gene (KCNE2.There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women.NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

  3. Inactivation of Bardet-Biedl syndrome genes causes kidney defects

    Science.gov (United States)

    Guo, Deng-Fu; Beyer, Andreas M.; Yang, Baoli; Nishimura, Darryl Y.; Sheffield, Val C.

    2011-01-01

    Bardet-Biedl syndrome (BBS) is a rare hereditary autosomal recessive disease associated with several features including obesity, hypertension, and renal abnormalities. The underlying mechanisms of renal defects associated with BBS remain poorly defined. We examined the histological, molecular, and functional renal changes in BBS mouse models that have features of the human disorder. Interestingly, obese hypertensive Bbs4−/− mice exhibited inflammatory infiltration and renal cysts, whereas the obese normotensive Bbs2−/− mice had only minor inflammatory infiltration. Accordingly, the expression level of inducible nitric oxide synthase was elevated in the kidney of both BBS mice with a more marked increase in Bbs4−/− mice. In contrast, endothelial nitric oxide synthase expression was decreased in Bbs4−/−, but not Bbs2−/−, mice. Similarly, the expression levels of transient receptor potential vanilloid 1 and 4 channels as well as β- and γ-subunits of epithelial Na channel were significantly reduced only in the kidney of Bbs4−/− mice. Metabolic studies revealed changes in urine output and urinary concentrations of creatinine, blood urea nitrogen, sodium, and potassium with a more pronounced effect in Bbs4−/− mice. Finally, we found that calorie restriction which prevented obesity in BBS mice reversed the morphological and molecular changes found in Bbs2−/− and Bbs4−/− mice, indicating the kidney abnormalities associated with BBS are obesity related. These findings extend our understanding of the function of BBS proteins and emphasize the importance of these proteins in renal physiology. PMID:21106857

  4. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

    Directory of Open Access Journals (Sweden)

    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  5. Biomarkers and genes predictive of disease predisposition and ...

    African Journals Online (AJOL)

    Biomarkers and genes predictive of disease predisposition and prognosis in rheumatoid arthritis. Rheumatoid arthritis is a debilitating disease which often progresses to relentlessly severe disease. Pieter W A Meyer, NHDip Med Tech, MTech, PhD. Medical Research Council Unit for Inflammation and Immunity, Department ...

  6. Web tools for the prioritization of candidate disease genes.

    NARCIS (Netherlands)

    Oti, M.O.; Ballouz, S.; Wouters, M.A.

    2011-01-01

    Despite increasing sequencing capacity, genetic disease investigation still frequently results in the identification of loci containing multiple candidate disease genes that need to be tested for involvement in the disease. This process can be expedited by prioritizing the candidates prior to

  7. Living with Restless Legs Syndrome/Willis-Ekbom Disease.

    Science.gov (United States)

    Tachibana, Naoko

    2015-09-01

    Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is commonly seen in patients with end-stage renal disease (ESRD), but this condition has not been properly recognized. The prevalence of RLS/WED in ESRD shows the ethnic variation (7%-68%), with the similar tendency of primary RLS/WED. Although RLS/WED in ESRD is defined in secondary RLS/WED, the factors of ESRD that are involved in the genesis of RLS/WED remain unknown. Even after renal transplantation, RLS/WED symptoms do not completely disappear, and genetic predisposition to RLS/WED may play an important role in causing RLS/WED. Long-term intervention for RLS/WED and ESRD will be necessary. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome.

    Science.gov (United States)

    Ü Basmanav, F Buket; Cau, Laura; Tafazzoli, Aylar; Méchin, Marie-Claire; Wolf, Sabrina; Romano, Maria Teresa; Valentin, Frederic; Wiegmann, Henning; Huchenq, Anne; Kandil, Rima; Garcia Bartels, Natalie; Kilic, Arzu; George, Susannah; Ralser, Damian J; Bergner, Stefan; Ferguson, David J P; Oprisoreanu, Ana-Maria; Wehner, Maria; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Swan, Daniel; Houniet, Darren; Büchner, Aline; Weibel, Lisa; Wagner, Nicola; Grimalt, Ramon; Bygum, Anette; Serre, Guy; Blume-Peytavi, Ulrike; Sprecher, Eli; Schoch, Susanne; Oji, Vinzenz; Hamm, Henning; Farrant, Paul; Simon, Michel; Betz, Regina C

    2016-12-01

    Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Muir-Torre Syndrome and founder mismatch repair gene mutations: A long gone historical genetic challenge.

    Science.gov (United States)

    Ponti, G; Manfredini, M; Tomasi, A; Pellacani, G

    2016-09-10

    A "cancer predisposing syndrome" later labeled as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch Syndrome, was firstly described by Warthin, about one century ago. An increased predisposition to the development of multiple familial tumors is described as characteristic of this syndrome where visceral and cutaneous malignancies may appear at an early age namely endometrial, gastric, small bowel, ureteral and renal pelvis, ovarian, hepatobiliary tract, pancreatic, brain (Turcot Syndrome) and sebaceous glands (Muir-Torre Syndrome). The latter, a variant of Lynch Syndrome, is characterized by the presence of sebaceous skin adenomas, carcinomas and/or keratoacanthomas associated with visceral malignancies. Both Lynch Syndrome and Muir-Torre Syndrome have been recognized due to germline mutations in mismatch repair genes MLH1, MSH2 and MSH6. To date, 56 Lynch Syndrome founder mutations dependent on MLH1, MSH2 and, although less frequently found, MSH6 and PMS2 are described. Some of these founder mutations, principally of MSH2 gene, have been described to cause Muir-Torre phenotype and have been traced in large and outbreed Muir-Torre Syndrome families living in different US and European territories. Due to the evidences of highly specific Muir-Torre phenotypes related to the presence of widespread MSH2 founder mutations, preliminary search for these MSH2 common mutations in individuals carrying sebaceous tumors and/or keratoacanthomas, at early age or in association to visceral and familial tumors, permits cost-effective and time-saving diagnostic strategies for Lynch/Muir-Torre Syndromes. Copyright © 2015. Published by Elsevier B.V.

  10. Antiphospholipid syndrome; its implication in cardiovascular diseases: a review

    Directory of Open Access Journals (Sweden)

    Goudevenos John

    2010-11-01

    Full Text Available Abstract Antiphospholipid syndrome (APLS is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL as anticardiolipin antibodies (aCL or lupus anticoagulant (LA. Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB. A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary.

  11. Myoclonic epilepsy in Down syndrome and Alzheimer disease.

    Science.gov (United States)

    Aller-Alvarez, J S; Menéndez-González, M; Ribacoba-Montero, R; Salvado, M; Vega, V; Suárez-Moro, R; Sueiras, M; Toledo, M; Salas-Puig, J; Álvarez-Sabin, J

    2017-03-01

    Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome.

    Science.gov (United States)

    Glintborg, Dorte; Andersen, Marianne

    2017-02-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance. Available data from register-based and data linkage studies support that metabolic-vascular and thyroid diseases, asthma, migraine, depression and cancer are diagnosed more frequently in PCOS, whereas fracture risk is decreased. Drug prescriptions are significantly more common in PCOS than controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long-term morbidity could be worsened by obesity, sedentary way of life, Western-style diet and smoking, whereas lifestyle intervention including weight loss may partly or fully resolve the symptoms of PCOS and could improve the long-term prognosis. In this review, the possible implications of increased morbidity for the clinical and biochemical evaluation of patients with PCOS at diagnosis and follow-up is further discussed along with possible modifying effects of medical treatment. © 2017 European Society of Endocrinology.

  13. Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS).

    Science.gov (United States)

    Brooks, Simon; Ebenezer, Neil; Poopalasundaram, Subathra; Maher, Eamonn; Francis, Peter; Moore, Anthony; Hardcastle, Alison

    2004-06-01

    The X-linked congenital cataract (CXN) locus has been mapped to a 3-cM (approximately 3.5 Mb) interval on chromosome Xp22.13, which is syntenic to the mouse cataract disease locus Xcat and encompasses the recently refined Nance-Horan syndrome (NHS) locus. A positional cloning strategy has been adopted to identify the causative gene. In an attempt to refine the CXN locus, seven microsatellites were analysed within 21 individuals of a CXN family. Haplotypes were reconstructed confirming disease segregation with markers on Xp22.13. In addition, a proximal cross-over was observed between markers S3 and S4, thereby refining the CXN disease interval by approximately 400 Kb to 3.2 Mb, flanked by markers DXS9902 and S4. Two known genes (RAI2 and RBBP7) and a novel gene (TL1) were screened for mutations within an affected male from the CXN family and an NHS family by direct sequencing of coding exons and intron- exon splice sites. No mutations or polymorphisms were identified, therefore excluding them as disease-causative in CXN and NHS. In conclusion, the CXN locus has been successfully refined and excludes PPEF1 as a candidate gene. A further three candidates were excluded based on sequence analysis. Future positional cloning efforts will focus on the region of overlap between CXN, Xcat, and NHS.

  14. IMPACT OF ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM ON THE DEVELOPMENT OF INSULIN RESISTANCE SYNDROME

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    G. E. Roitberg

    2013-01-01

    Full Text Available Objective: to analyze the distribution of components of insulin resistance (IR syndrome and to study the frequency of their combinations in relation to the genotypes and allelic variants of the angiotensin-converting enzyme (ACE gene.Subjects and methods. A group of clinically healthy patients (50 women and 42 men with different genotypes of the ACE gene was examined.The distribution of IR syndrome components and the frequency of their combinations were analyzed in relation to the genotypes and allelicvariants of the ACE gene.Results. A group of D allele carriers compared to A allele ones showed a pronounced tendency for the frequency of IR to reduce due to thehigher proportion of patients with complete IR syndrome. This observation becomes statistically significant in the assessment of homozygous variants of the ACE gene. At the same time dyslipidemia and hypertension in the presence of IR significantly more frequently occurred in patients with the DD genotype than in those with genotype II.Conclusion. There was a marked predominance of the manifestations of IR syndrome with a complete set of components in the DD genotypicgroup, which confirms the significant strong association between ACE gene polymorphism and IR syndrome.

  15. Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development

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    Vitalis Tania

    2009-03-01

    Full Text Available Abstract Background Down syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. The mechanisms by which this aneuploidy produces the complex and variable phenotype observed in people with Down syndrome are still under discussion. Recent studies have demonstrated an increased transcript level of the three-copy genes with some dosage compensation or amplification for a subset of them. The impact of this gene dosage effect on the whole transcriptome is still debated and longitudinal studies assessing the variability among samples, tissues and developmental stages are needed. Results We thus designed a large scale gene expression study in mice (the Ts1Cje Down syndrome mouse model in which we could measure the effects of trisomy 21 on a large number of samples (74 in total in a tissue that is affected in Down syndrome (the cerebellum and where we could quantify the defect during postnatal development in order to correlate gene expression changes to the phenotype observed. Statistical analysis of microarray data revealed a major gene dosage effect: for the three-copy genes as well as for a 2 Mb segment from mouse chromosome 12 that we show for the first time as being deleted in the Ts1Cje mice. This gene dosage effect impacts moderately on the expression of euploid genes (2.4 to 7.5% differentially expressed. Only 13 genes were significantly dysregulated in Ts1Cje mice at all four postnatal development stages studied from birth to 10 days after birth, and among them are 6 three-copy genes. The decrease in granule cell proliferation demonstrated in newborn Ts1Cje cerebellum was correlated with a major gene dosage effect on the transcriptome in dissected cerebellar external granule cell layer. Conclusion High throughput gene expression analysis in the cerebellum of a large number of samples of Ts1Cje and euploid mice has revealed a prevailing gene dosage effect on triplicated genes. Moreover using an enriched cell

  16. Prioritization of candidate disease genes by topological similarity between disease and protein diffusion profiles.

    Science.gov (United States)

    Zhu, Jie; Qin, Yufang; Liu, Taigang; Wang, Jun; Zheng, Xiaoqi

    2013-01-01

    Identification of gene-phenotype relationships is a fundamental challenge in human health clinic. Based on the observation that genes causing the same or similar phenotypes tend to correlate with each other in the protein-protein interaction network, a lot of network-based approaches were proposed based on different underlying models. A recent comparative study showed that diffusion-based methods achieve the state-of-the-art predictive performance. In this paper, a new diffusion-based method was proposed to prioritize candidate disease genes. Diffusion profile of a disease was defined as the stationary distribution of candidate genes given a random walk with restart where similarities between phenotypes are incorporated. Then, candidate disease genes are prioritized by comparing their diffusion profiles with that of the disease. Finally, the effectiveness of our method was demonstrated through the leave-one-out cross-validation against control genes from artificial linkage intervals and randomly chosen genes. Comparative study showed that our method achieves improved performance compared to some classical diffusion-based methods. To further illustrate our method, we used our algorithm to predict new causing genes of 16 multifactorial diseases including Prostate cancer and Alzheimer's disease, and the top predictions were in good consistent with literature reports. Our study indicates that integration of multiple information sources, especially the phenotype similarity profile data, and introduction of global similarity measure between disease and gene diffusion profiles are helpful for prioritizing candidate disease genes. Programs and data are available upon request.

  17. Intergenerational associations of chronic disease and polycystic ovary syndrome.

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    Michael J Davies

    Full Text Available BACKGROUND: Polycystic ovary syndrome (PCOS is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. OBJECTIVE: To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. DESIGN, SETTING AND PARTICIPANTS: Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. RESULTS AND CONCLUSIONS: Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47, and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76. Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88 and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70. Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.

  18. A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

    OpenAIRE

    Salehi, Nooshin; Choi, Eric D.; Garrison, Roger C.

    2017-01-01

    Patient: Male, 32 Final Diagnosis: Miller Fisher syndrome Symptoms: Ataxia ? headache ? ophthalmoplegia Medication: ? Clinical Procedure: Plasmapheresis Specialty: Neurology Objective: Rare co-existance of disease or pathology Background: Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1?5% of all Guillain-Barre cases in Wes...

  19. Humoral Immunity in Children with Down Syndrome: relevance to respiratory disease

    OpenAIRE

    Verstegen, Ruud

    2015-01-01

    markdownabstract__Abstract__ Down syndrome is the most common cause of developmental delay in humans. In The Netherlands, each year approximately 250 children with Down syndrome are born. Individuals with Down syndrome suffer from increased incidences of respiratory tract infections, autoimmune disease and haematological malignancies. This triad is reminiscent of immunodefi ciencies and has led to the hypothesis of an altered immune system in Down syndrome. The high incidence of respiratory t...

  20. 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.

  1. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease

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    Mitra Souvik

    2010-10-01

    Full Text Available Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan′s anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.

  2. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

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    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A; Sanz, Ferran; Furlong, Laura I

    2011-01-01

    Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The

  3. A novel mutation in the endothelin B receptor gene in a moroccan family with shah-waardenburg syndrome.

    Science.gov (United States)

    Doubaj, Yassamine; Pingault, Véronique; Elalaoui, Siham C; Ratbi, Ilham; Azouz, Mohamed; Zerhouni, Hicham; Ettayebi, Fouad; Sefiani, Abdelaziz

    2015-02-01

    Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural deafness and pigmentary abnormalities. The presence of additional signs defines the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is characterized by the association with congenital aganglionic megacolon (Hirschsprung disease). To date, 3 causative genes have been related to this congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl with WS type IV, born to consanguineous parents. The patient had 3 cousins who died in infancy with the same symptoms. Molecular analysis by Sanger sequencing revealed the presence of a novel homozygous missense mutation c.1133A>G (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of the deceased cousins are heterozygous carriers of this likely pathogenic mutation. This molecular diagnosis allows us to provide genetic counseling to the family and eventually propose prenatal diagnosis to prevent recurrence of the disease in subsequent pregnancies.

  4. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

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    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  5. Disease Control in Animals Using Molecular Technology by Inactivation of ASO, RNAi and ss-siRNA Genes

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    Muhamad Ali

    2014-03-01

    Full Text Available Globalization causes high mobility of human and livestock, hence increase the transmission of infectious diseases, including avian influenza, severe acute respiratory syndrome (SARS, and swine influenza. Therefore, prevention of those diseases is required. Vaccines are effective to prevent infectious diseases; however, their development takes a long time and they cannot provide immediate protection in pandemic cases. This paper describes several gene silencing technologies including antisense oligonucleotide (ASO, RNA interference (RNAi and single strand-small interfering RNA (ss-siRNA for controlling diseases. The primary mechanism of these technologies is inhibition of gene expression, typically by causing the destruction of specific RNA molecule of the pathogen. The use of gene silencing technologies is expected to give new alternative that is more effective in eradication of infectious diseases in animals before threaten human being.

  6. Orthopaedic Aspects of Marfan Syndrome: The Experience of a Referral Center for Diagnosis of Rare Diseases

    Science.gov (United States)

    Fichera, Alessandro; De Luna, Vincenzo; Mancini, Federico; Caterini, Roberto

    2016-01-01

    Marfan syndrome is caused by mutations in the fibrillin-1 gene (FBN1). The most important features affect the cardiovascular system, eyes, and skeleton. The aim of this study was to report the most frequent musculoskeletal alterations observed in 146 patients affected by Marfan syndrome. Fifty-four patients (37%) underwent cardiac surgery and 11 of them received emergent surgery for acute aortic dissection. Ectopia lentis was found in 68 patients (47%) whereas myopia above 3D occurred in 46 patients (32%). Musculoskeletal anomalies were observed in all patients with Marfan syndrome. In 88 patients (60.2%), the associated “wrist and thumb sign” was present; in 58 patients (39.7%), pectus carinatum deformity; in 44 patients (30.1%), pectus excavatum; in 49 patients (33.5%), severe flatfoot; in 31 patients (21.2%), hindfoot deformity; in 54 patients (36.9%), reduced US/LS ratio or increased arm span-height ratio; in 37 patients (25.3%), scoliosis or thoracolumbar kyphosis; in 22 patients (15%), reduced elbow extension (170° or less). Acetabular protrusion was ascertained on radiographs in 27 patients (18.4%). Orthopaedic aspects of the disease are very important for an early diagnosis; however, we have not observed definite correlations between the extent of orthopaedic involvement and aortic complications. PMID:28050285

  7. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype.

    Science.gov (United States)

    de Heredia, Miguel López; Clèries, Ramón; Nunes, Virginia

    2013-07-01

    Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. (i) 15% of published patients do not fulfill the current -inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient's genotypic class; and (vi) disease progression rate might depend on genotypic class. New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

  8. Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease.

    Science.gov (United States)

    Lieber, Daniel S; Vafai, Scott B; Horton, Laura C; Slate, Nancy G; Liu, Shangtao; Borowsky, Mark L; Calvo, Sarah E; Schmahmann, Jeremy D; Mootha, Vamsi K

    2012-01-06

    Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

  9. Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease

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    Lieber Daniel S

    2012-01-01

    Full Text Available Abstract Background Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

  10. Nucleotide sequence analysis of NIPBL gene in Indian Cornelia de Lange syndrome cases.

    Science.gov (United States)

    Bajaj, Shailesh; Ranade, Suvidya; Gambhir, Prakash

    2013-01-01

    Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder in children. The disorder is caused mainly due to mutations in Nipped-B-like protein. The molecular data for CdLS is available from developed countries, but not available in developing countries like India. In the present study, the hotspot region of NIPBL gene was screened by Polymerase Chain Reaction which includes exon 2, 22, 42, and a biggest exon 10, in six CdLS patients and ten controls. The method adopted in present study was amplification of the target exon by using polymerase chain reaction, qualitative confirmation of amplicons by Agarose Gel Electrophoresis and use of amplicons for Conformation Sensitive Gel Electrophoresis to find heteroduplex formation followed by sequencing. We report two polymorphisms in the studied region of gene NIPBL. The polymorphisms are in the region of intron 1 and in exon 10. The polymorphism C/A is present in intron 1 region and polymorphism T/G in exon 10. The intronic region polymorphism may have a role in intron splicing whereas the polymorphism in exon 10 results in amino acid change (Val to Gly). These polymorphisms are disease associated as these are found in CdLS patients only and not in controls.

  11. Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome

    Science.gov (United States)

    2014-01-01

    Background Bicuspid aortic valve (BAV) is the most frequent congenital heart disease with frequent involvement in thoracic aortic dilatation, aneurysm and dissection. Although BAV and Marfan syndrome (MFS) share some clinical features, and some MFS patients with BAV display mutations in FBN1, the gene encoding fibrillin-1, the genetic background of isolated BAV is poorly defined. Methods Ten consecutive BAV patients [8 men, age range 24–42 years] without MFS were clinically characterized. BAV phenotype and function, together with evaluation of aortic morphology, were comprehensively assessed by Doppler echocardiography. Direct sequencing of each FBN1 exon with flanking intron sequences was performed on eight patients. Results We detected three FBN1 mutations in two patients (aged 24 and 25 years) displaying aortic root aneurysm ≥50 mm and moderate aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp and p.Arg636Gly) one of which has been previously associated with variable Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported to be associated with an incomplete MFS phenotype. Conclusions The present findings enlarge the clinical spectrum of isolated BAV to include patients with BAV without MFS who have involvement of FBN1 gene. These results underscore the importance of accurate phenotyping of BAV aortopathy and of clinical characterization of BAV patients, including investigation of systemic connective tissue manifestations and genetic testing. PMID:24564502

  12. Cataract as a phenotypic marker for a mutation in WFS1, the Wolfram syndrome gene.

    Science.gov (United States)

    Titah, Salah Mohamed Cherif; Meunier, Isabelle; Blanchet, Catherine; Lopez, Severine; Rondouin, Gerard; Lenaers, Guy; Amati-Bonneau, Patrizia; Reynier, Pascal; Paquis-Flucklinger, Veronique; Hamel, Christian P

    2012-01-01

    Wolfram syndrome (WS) or diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) (OMIM 222300) is an inherited neurodegenerative disease characterized by diabetes mellitus and optic atrophy as the 2 major criteria, followed later in life by deafness, diabetes insipidus, and various signs of neurologic impairment. The presence of a cataract has been variably mentioned in WS. Two members of a family had thorough ophthalmic examination and their DNA was screened for mutations in mitochondrial DNA, WFS1, OPA1, and OPA3 genes. We report a patient who first had surgery for bilateral cataract at age 5 and who subsequently presented typical signs of WS, i.e., diabetes mellitus, optic atrophy with reduced visual acuity at 20/400 on both eyes at age 22, and mild deafness. The patient was found to be a compound heterozygote for 2 truncating mutations in WFS1, the major WS gene. She carried the previously reported c.1231_1233 delCT and a novel c.2431_2465dup35 mutation. She also was heterozygote for a novel OPA1 sequence variant, c.929A>G in exon 9, whose pathogenicity remains uncertain. The patient's mother was a heterozygous carrier of the c.2431_2465dup35 mutation. She did not have diabetes mellitus or optic atrophy but had bilateral polar cataract. She did not carry the OPA1 sequence variant. Cataract could be a marker for the WFS1 heterozygosity in this family, namely the c.2431_2465dup35 mutation.

  13. A survey of disease connections for CD4+ T cell master genes and their directly linked genes.

    Science.gov (United States)

    Li, Wentian; Espinal-Enríquez, Jesús; Simpfendorfer, Kim R; Hernández-Lemus, Enrique

    2015-12-01

    Genome-wide association studies and other genetic analyses have identified a large number of genes and variants implicating a variety of disease etiological mechanisms. It is imperative for the study of human diseases to put these genetic findings into a coherent functional context. Here we use system biology tools to examine disease connections of five master genes for CD4+ T cell subtypes (TBX21, GATA3, RORC, BCL6, and FOXP3). We compiled a list of genes functionally interacting (protein-protein interaction, or by acting in the same pathway) with the master genes, then we surveyed the disease connections, either by experimental evidence or by genetic association. Embryonic lethal genes (also known as essential genes) are over-represented in master genes and their interacting genes (55% versus 40% in other genes). Transcription factors are significantly enriched among genes interacting with the master genes (63% versus 10% in other genes). Predicted haploinsufficiency is a feature of most these genes. Disease-connected genes are enriched in this list of genes: 42% of these genes have a disease connection according to Online Mendelian Inheritance in Man (OMIM) (versus 23% in other genes), and 74% are associated with some diseases or phenotype in a Genome Wide Association Study (GWAS) (versus 43% in other genes). Seemingly, not all of the diseases connected to genes surveyed were immune related, which may indicate pleiotropic functions of the master regulator genes and associated genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

    Directory of Open Access Journals (Sweden)

    L Simo-Riudalbas

    Full Text Available Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9, marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues.In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific

  15. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

    Science.gov (United States)

    Simo-Riudalbas, L; Diaz-Lagares, A; Gatto, S; Gagliardi, M; Crujeiras, A B; Matarazzo, M R; Esteller, M; Sandoval, J

    2015-01-01

    Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers

  16. A novel single point mutation of the LYST gene in two siblings with different phenotypic features of Chediak Higashi syndrome.

    Science.gov (United States)

    Kaya, Zuhre; Ehl, Stephan; Albayrak, Meryem; Maul-Pavicic, Andrea; Schwarz, Klaus; Kocak, Ulker; Ergun, Mehmet Ali; Gursel, Turkiz

    2011-07-01

    Chediak Higashi syndrome (CHS) is an autosomal-recessive disorder characterized by oculocutaneous albinism, recurrent infections and a progressive primary neurological disease. Here, we describe two siblings with CHS due to a novel homozygous R1836X mutation in the LYST gene associated with loss of NK cell degranulation and cytotoxicity. While one sibling was born with fair skin and hair and died of hemophagocytic lymphohistiocytosis (HLH) at 5 months of age, the other sibling had dark black hair and skin and developed HLH at the age of 4 years. Copyright © 2011 Wiley-Liss, Inc.

  17. Restless legs syndrome associated with major diseases: A systematic review and new concept.

    Science.gov (United States)

    Trenkwalder, Claudia; Allen, Richard; Högl, Birgit; Paulus, Walter; Winkelmann, Juliane

    2016-04-05

    Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene-microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other. © 2016 American Academy of Neurology.

  18. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

    Science.gov (United States)

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

  19. Epizootic ulcerative syndrome: exotic fish disease threatens Africa's aquatic ecosystems.

    Science.gov (United States)

    Huchzermeyer, Karl D A; van der Waal, Benjamin C W

    2012-09-25

    In late 2006 an unusual ulcerative condition in wild fish was reported for the first time in Africa from the Chobe and upper Zambezi Rivers in Botswana and Namibia. Concern increased with subsistence fishermen reporting large numbers of ulcerated fish in their catches. In April 2007 the condition was confirmed as an outbreak of epizootic ulcerative syndrome (EUS). The causative agent, Aphanomyces invadans, is a pathogenic water mould of fish that shows little host specificity. Ulcers follow infection of tissues by oomycete zoospores, resulting in a granulomatous inflammation associated with invading oomycete hyphae. Granulomatous tracts surrounding oomycete hyphae within the necrotic tissues characterise the diagnostic histological picture. The upper Zambezi floodplain at the confluence with the Chobe River spans the four countries of Botswana, Namibia, Zambia and Zimbabwe, making disease control a challenge. The floodplain ecosystem supports a high fish diversity of around 80 species, and is an important breeding and nursery ground. The annual cycle of flooding brings about changes in water quality that are thought to favour the infectivity of A. invadans, with diseased fish appearing soon after the plains become flooded. Since 2006 the disease has spread rapidly upstream along the upper Zambezi and its tributaries. By 2010 the disease was reported from the Okavango Delta in Botswana and in 2011 from the Western Cape Province of South Africa. EUS has the potential to disrupt floodplain ecosystems elsewhere in Africa where high fish diversity forms the basis of subsistence fisheries and local economies, and is a direct threat to freshwater fish culture.

  20. Porites white patch syndrome: associated viruses and disease physiology

    Science.gov (United States)

    Lawrence, S. A.; Davy, J. E.; Wilson, W. H.; Hoegh-Guldberg, O.; Davy, S. K.

    2015-03-01

    In recent decades, coral reefs worldwide have undergone significant changes in response to various environmental and anthropogenic impacts. Among the numerous causes of reef degradation, coral disease is one factor that is to a large extent still poorly understood. Here, we characterize the physiology of white patch syndrome (WPS), a disease affecting poritid corals on the Great Barrier Reef. WPS manifests as small, generally discrete patches of tissue discolouration. Physiological analysis revealed that chlorophyll a content was significantly lower in lesions than in healthy tissues, while host protein content remained constant, suggesting that host tissue is not affected by WPS. This was confirmed by transmission electron microscope (TEM) examination, which showed intact host tissue within lesions. TEM also revealed that Symbiodinium cells are lost from the host gastrodermis with no apparent harm caused to the surrounding host tissue. Also present in the electron micrographs were numerous virus-like particles (VLPs), in both coral and Symbiodinium cells. Small (cells from diseased colonies. There was no apparent increase in prokaryotic or eukaryotic microbial abundance in diseased colonies. Taken together, these results suggest that viruses infecting the coral and/or its resident Symbiodinium cells may be the causative agents of WPS.

  1. Acute Chest Syndrome in Children with Sickle Cell Disease

    Science.gov (United States)

    Bakshi, Nitya; Krishnamurti, Lakshmanan

    2017-01-01

    Acute chest syndrome (ACS) is a frequent cause of acute lung disease in children with sickle cell disease (SCD). Patients may present with ACS or may develop this complication during the course of a hospitalization for acute vaso-occlusive crises (VOC). ACS is associated with prolonged hospitalization, increased risk of respiratory failure, and the potential for developing chronic lung disease. ACS in SCD is defined as the presence of fever and/or new respiratory symptoms accompanied by the presence of a new pulmonary infiltrate on chest X-ray. The spectrum of clinical manifestations can range from mild respiratory illness to acute respiratory distress syndrome. The presence of severe hypoxemia is a useful predictor of severity and outcome. The etiology of ACS is often multifactorial. One of the proposed mechanisms involves increased adhesion of sickle red cells to pulmonary microvasculature in the presence of hypoxia. Other commonly associated etiologies include infection, pulmonary fat embolism, and infarction. Infection is a common cause in children, whereas adults usually present with pain crises. Several risk factors have been identified in children to be associated with increased incidence of ACS. These include younger age, severe SCD genotypes (SS or Sβ0 thalassemia), lower fetal hemoglobin concentrations, higher steady-state hemoglobin levels, higher steady-state white blood cell counts, history of asthma, and tobacco smoke exposure. Opiate overdose and resulting hypoventilation can also trigger ACS. Prompt diagnosis and management with intravenous fluids, analgesics, aggressive incentive spirometry, supplemental oxygen or respiratory support, antibiotics, and transfusion therapy, are key to the prevention of clinical deterioration. Bronchodilators should be considered if there is history of asthma or in the presence of acute bronchospasm. Treatment with hydroxyurea should be considered for prevention of recurrent episodes. This review evaluates the

  2. Polymorphisms in genes RFC-1/CBS as maternal risk factors for Down syndrome in China.

    Science.gov (United States)

    Wang, Shao-shuai; Wang, Chao; Qiao, Fu-yuan; Lv, Juan-juan; Feng, Ling

    2013-08-01

    To explore the relationship between genetic polymorphisms in reduced folate carrier 1 (RFC-1), cystathionine b-synthase (CBS), two key genes in folate metabolism, and the risk of Down syndrome in China. Genomic DNA was isolated from the peripheral lymphocytes of 104 mothers born children with Down syndrome and 184 age-matched control mothers. Polymerase chain reaction and restriction-fragment length polymorphism were used to examine the polymorphisms of RFC-1 A80G, CBS T833C and the relationship between these genotypes and the risk of Down syndrome was analyzed. We found that there were significant differences between RFC-1 G80G, CBS C833C polymorphisms among mothers of children with Down syndrome than among control mothers, with odds ratio of 1.51 (95 % CI 1.05-2.18), 1.53 (95 % CI 1.07-2.18) respectively. The combined presence of RFC1 mutant alleles and the CBS homozygous mutant allele (15/104) was associated with a 4.81-fold increased risk of having a child with Down syndrome (95 % CI 1.82-12.68, P = 0.0007). We concluded that RFC-1 and CBS gene mutation alleles are related to Down syndrome, and women with mutation RFC-1 G80G, CBS C833C OR combined with RFC-1 A80G and CBS 833TT genotype increase the risk of Down syndrome in China.

  3. Expression of VP60 gene from rabbit haemorrhagic disease virus ...

    African Journals Online (AJOL)

    The VP60 gene from rabbit haemorrhagic disease virus (RHDV) YL strain in Northeast of China, under control of the ats1A promoter from Rubisco small subunit genes of Arabidopsis thaliana, was introduced into the transfer deoxyribonucleic acid (T-DNA) region of plant transfer vector pCAMBIA1300 and transferred to ...

  4. Molecular detection of disease resistance genes to powdery mildew ...

    African Journals Online (AJOL)

    A study was conducted to detect the presence of disease resistance genes to infection of wheat powdery mildew (Blumeria graminis f. sp. tritici) in selected wheat cultivars from China using molecular markers. Genomic DNA of sixty cultivars was extracted and tested for the presence of selected prominent resistance genes to ...

  5. Vitamin D receptor gene variants in Parkinson's disease patients ...

    African Journals Online (AJOL)

    Background: Vitamin D plays an important role in neurodegenerative disorders as a crucial neuro-immunomodulator. Accumulating data provide evidences that vitamin D receptor (VDR) gene is a candidate gene for susceptibility to Parkinson's disease (PD). Aim: To find out whether the risk of the development of sporadic ...

  6. A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype.

    Science.gov (United States)

    Romaniello, Romina; Saettini, Francesco; Panzeri, Elena; Arrigoni, Filippo; Bassi, Maria T; Borgatti, Renato

    2015-03-25

    This study reports on a 9-year-old girl who developed West syndrome and showed clinical features fulfilling the main revised diagnostic criteria for typical Rett syndrome (hand washing, severe cognitive impairment with absence of language, ataxic gait, progressive scoliosis and autistic features). Mutation analyses for methyl-CpG-binding protein 2 (MECP2), cyclin-dependent kinase-like 5 (CDKL5/STK9), ARX and Forkhead box G1 (FOXG1) genes were carried out, with negative results. A known de-novo c.1217G>A missense mutation in exon 14 leading to the substitution of a conserved residue, p.R406H in domain3b of the syntaxin-binding protein 1 (STXBP1) gene, was detected. The STXBP1 gene encodes the syntaxin-binding protein 1, a neuron-specific protein involved in synaptic vesicle release at both glutaminergic and GABAergic synapses. This function is also affected by MECP2 gene mutations, which are known to lead to a decrease in glutamate and GABA receptors' density. It is possible to speculate that the impairment in synaptic plasticity represents the pathogenic link between MECP2 and STXBP1 gene mutations. On reviewing the clinical features of the reported patients with the same mutation in the STXBP1 gene, it has been observed that poor eye contact, tremour, dyskinesia, head/hand stereotypies and both cognitive and motor progressive deterioration are common symptoms, although never considered as indicative of a Rett syndrome phenotype. In conclusion, the case described here suggests a relationship between the Rett syndrome and the STXBP1 gene not described so far, making the search for STXBP1 gene mutations advisable in patients with Rett syndrome and early onset of epilepsy. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  7. Strengthening research on relationship between metabolic syndrome and chronic liver disease

    Directory of Open Access Journals (Sweden)

    FAN Jiangao

    2013-12-01

    Full Text Available Metabolic syndrome is becoming a global epidemic disease, and it has been an important cause or risk factor for chronic liver disease in China. Recently, many studies have shown that metabolic syndrome is not only the important cause or risk factor for non-alcoholic fatty liver disease, but also closely associated with increased incidence of cirrhosis and liver cancer in patients with alcoholic liver disease, chronic hepatitis B and C, and cryptogenic liver disease. Moreover, chronic liver disease patients with metabolic syndrome have a significantly increased risk of type 2 diabetes and arteriosclerotic cardiovascular disease. These results suggest that hepatologists should pay more attention to the clinical research on the relationship between metabolic syndrome and liver disease and its management.

  8. Gene-environment interaction in atopic diseases

    DEFF Research Database (Denmark)

    Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff

    2015-01-01

    INTRODUCTION: The development of atopic diseases early in life suggests an important role of perinatal risk factors. OBJECTIVES: To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. METHODS: Questionnaire data on atopic diseases from 850....... Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. RESULTS: After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI...... stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. CONCLUSION: In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors...

  9. Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down syndrome screening

    NARCIS (Netherlands)

    Pennings, J.L.A.; Rodenburg, W.; Imholz, S.; Koster, M.P.H.; van Oostrom, C.T.M.; Breit, T.M.; Schielen, P.C.J.I.; de Vries, A.

    2011-01-01

    Background: As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues

  10. Tagging of resistance gene(s) to rhizomania disease in sugar beet ...

    African Journals Online (AJOL)

    The rhizomania disease is one of the most important diseases in Iran and some other parts of the world which potentially could play a role in decreasing sugar yield in fields. One approach to combat with this disease is the use of resistance varieties. This varieties have been identified which are having resistance genes to ...

  11. Disease: H01243 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01243 Huntington's disease-like syndrome Huntington's disease (HD), which is caus...description, gene) ... AUTHORS ... Schneider SA, Walker RH, Bhatia KP ... TITLE ... The Huntington's disease-like ...syndromes: what to consider in patients with a negative Huntington's disease gene

  12. Nicolau's syndrome: A rare but preventable iatrogenic disease.

    Science.gov (United States)

    Adil, Mohammad; Amin, Syed Suhail; Arif, Tasleem

    2017-10-01

    the gluteal region, extending to the lateral aspect of thigh (Figure 2). It was tender to the touch, non-indurated, and the local temperature was raised. There was no regional lymphadenopathy. No other abnormality was detected on examination. All routine investigations were within normal limits. Platelet count, bleeding, clotting and prothrombin times, and international normalized ratio (INR) were within normal limits. The lesions resolved within few weeks without any complications. Nicolau syndrome was first described in the early 1920s by Freudenthal and Nicolau as an adverse effect of using intramuscular injections of bismuth salts in the treatment of syphilis. Since then, several case reports of this disease occurring after intramuscular, intra-articular, intravenous, and subcutaneous injections have appeared in the literature associated with a variety of drugs like NSAIDs, vitamin K, penicillin, antihistamines, corticosteroids, local anesthetics, vaccines, polidocanol, and pegylated interferon alpha (1). The pathogenesis of Nicolau syndrome is unknown, though intra and periarterial injection of the drug is a possible cause. Stimulation of the sympathetic nerve due to periarterial injection causes spasms and consequent ischemia. Inadvertent intra-arterial injections may cause emboli and occlusion. A lipophilic drug may penetrate the vessel and produce physical occlusion like fat embolism. Cytotoxic drugs may produce perivascular inflammation and ischemic necrosis. NSAIDs are believed to additionally induce ischemic necrosis due to their inhibition of cyclooxygenase and, consequently, prostaglandins (2). The clinical features of the disease have been divided into three phases in a review by Kim et al. (3). The authors describe an initial phase characterized by intense pain with subsequent erythema. This is followed 1-3 days later by an acute phase, when an indurated, tender plaque with livedoid pattern develops. The final phase occurs between 5 days and 2 weeks

  13. Fragile X syndrome – a common disease rarely diagnosed

    Directory of Open Access Journals (Sweden)

    Lisik Malgorzata Zofia

    2017-03-01

    Full Text Available Fragile X syndrome (FXS is a single-gene disorder with a broad spectrum of involvement, including cognitive and behavioural impairments of varying degrees with specific physical features and with strong association with autism. The study was conducted on 23 males (10-32 years old who had full mutation in the FMR1 gene. A complete medical evaluation, including medical history, family history, psychological testing and physical examination was conducted on each subject. Three of the FXS patients (13% were isolated cases of mental retardation in the family. The remaining 20 FXS patients belonged to 15 families, where there were other mentally retarded family members present. The degree of mental retardation (MR varied. Mild MR was diagnosed in 1/23 (4.35%, moderate MR in 12/23 (52.17%, severe MR in 10/23 (43.48 %. Moreover, autism spectrum disorder was diagnosed in 5/23 (21.74% FXS patients. Analysis of the BMI showed that in FXS patients, 14 of 23 (60.68% had too high body weight - 9/23 (39.13% were overweight and 5/23 (21.74% were obese. The diagnosis of FXS is difficult because of nonspecific symptoms, yet early diagnosis is crucial for early intervention and genetic counseling. The risk of recurrence is 50%.

  14. [A patient with coexistence of primary hyperparathyroidism, Marfan's syndrome and von Willebrand's disease].

    Science.gov (United States)

    Bednarek-Tupikowska, Grazyna; Rakowska-Chort, Anna; Adamarczuk-Janczyszyn, Maria

    2008-01-01

    We presented a case of a 58 year old women suffering from three diseases: primary hyperparathyroidism, Marfan's syndrome and von Willebrand's disease. The coexistence of these diseases is not mentioned in medical literature. Because of the coexistence of Marfan's syndrome with primary hyperparathyroidism, the examinations of other endocrinopathy including multiple endocrine neoplasia (MEN). Their coexistence was not confirmed at the present time. In this paper the new views on both patogenesis and treatment of the mentioned diseases were included.

  15. Nonfamilial Juvenile Polyposis Syndrome with Exon 5 Novel Mutation in SMAD 4 Gene

    OpenAIRE

    Ahmed, Amna; Alsaleem, Badr

    2017-01-01

    Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder, characterized by multiple juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. JPS is most frequently caused by mutations in the SMAD4 or BMPR1A genes. Herein, we report a child with juvenile polyposis syndrome (JPS) with a novel mutation in the SMAD4 gene. An 8-year-old boy presented with recurrent rectal bleeding and was found to have multiple polyps in the entire colon. ...

  16. Gene editing as a promising approach for respiratory diseases.

    Science.gov (United States)

    Bai, Yichun; Liu, Yang; Su, Zhenlei; Ma, Yana; Ren, Chonghua; Zhao, Runzhen; Ji, Hong-Long

    2018-03-01

    Respiratory diseases, which are leading causes of mortality and morbidity in the world, are dysfunctions of the nasopharynx, the trachea, the bronchus, the lung and the pleural cavity. Symptoms of chronic respiratory diseases, such as cough, sneezing and difficulty breathing, may seriously affect the productivity, sleep quality and physical and mental well-being of patients, and patients with acute respiratory diseases may have difficulty breathing, anoxia and even life-threatening respiratory failure. Respiratory diseases are generally heterogeneous, with multifaceted causes including smoking, ageing, air pollution, infection and gene mutations. Clinically, a single pulmonary disease can exhibit more than one phenotype or coexist with multiple organ disorders. To correct abnormal function or repair injured respiratory tissues, one of the most promising techniques is to correct mutated genes by gene editing, as some gene mutations have been clearly demonstrated to be associated with genetic or heterogeneous respiratory diseases. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) systems are three innovative gene editing technologies developed recently. In this short review, we have summarised the structure and operating principles of the ZFNs, TALENs and CRISPR/Cas9 systems and their preclinical and clinical applications in respiratory diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. The superior vena cava syndrome caused by malignant disease

    International Nuclear Information System (INIS)

    Eren, Suat; Karaman, Adem; Okur, Adnan

    2006-01-01

    Objective: The superior vena cava (SVC) obstruction by malignant diseases is either by direct invasion and compression or by tumour thrombus of the SVC. Whatever is its cause, obstruction of the SVC causes elevated pressure in the veins draining into the SVC and increased or reversed blood flow through collateral vessels. Severity of the syndrome depends on the collateral vascular system development. Therefore, imaging of the collateral veins with variable location and connection is important in determining the extension and management of the disease. Our aims are to describe collateral vessels of the superior vena cava syndrome (SVCS) related with the malignant diseases and to assess the ability of multi-detector row CT with multiplanar and 3D volume rendering techniques in determining and describing collateral circulations. Materials and methods: We present CT angiography findings of seven patients with small cell carcinoma of the lung (n = 2), squamous cell carcinoma of the lung (n = 3), Hodgkin disease of the thorax (n = 1), and squamous cell carcinoma of the oesophagus (n = 1). The patients received contrast-enhanced CT scans of the chest and abdomen on a multi-detector row CT during breath holding at suspended inspiration. Results: CT images revealed the cause and level of the SVC obstruction in all patients with axial and multiplanar reconstructed images. The SVC showed total obstruction in five patients and partial obstruction in two patients. The most common experienced collateral vessels were azygos vein (6), intercostal veins (6), mediastinal veins (6), paravertebral veins (5), hemiazygos vein (5), thoracoepigastric vein (5), internal mammary vein (5), thoracoacromioclavicular venous plexus (5), and anterior chest wall veins (5). While one case showed the portal-systemic shunt, V. cordis media and sinus coronarius with phrenic veins were enlarged in two cases, and the left adrenal vein was enlarged in a patient. In one case, the azygos vein with reversed

  18. Itai-itai disease is not associated with polymorphisms of the estrogen receptor {alpha} gene

    Energy Technology Data Exchange (ETDEWEB)

    Nishio, Hisahide; Hayashi, Chiyo; Lee, Myeongjin; Ayaki, Hitoshi; Sumino, Kimiaki [Kobe Univ. School of Medicine (Japan). Dept. of Public Health; Yamamoto, Ryoji; Ninomiya, Ruriko; Koizumi, Naoko [Hyogo College of Medicine (Japan). Dept. of Public Health

    1999-11-01

    Itai-itai (or ouch-ouch) disease is a syndrome accompanied by bone mineral disorders, and which may be related to oral cadmium exposure. Itai-itai predominantly affects postmenopausal women with a history of multiple childbirths. Recently, it has been reported that polymorphisms of the estrogen receptor {alpha} (ER{alpha}) gene are associated with postmenopausal reduction of bone mineral density in Japanese women. However, estrogen receptors have never been studied in itai-itai disease. In this study, we examined the genotypic distributions of PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of the ER{alpha} gene in patients with itai-itai disease and compared them with those of control subjects. The RFLPs are represented here as P{sub p} (PvuII) and Xx (XbaI); the capital and small letters signify the absence and presence of restriction sites, respectively. The genotypic distributions of the patient group were: PP, 14.8%; Pp, 55.6%; pp, 29.6%; XX, 7.4%; Xx, 29.6%; and xx, 63.0%. These distributions were similar to those observed for the control groups, hence no pattern of genotypic distribution was observed that could be related to itai-itai disease. We conclude that RFLPs of the ER{alpha} gene may not be associated with itai-itai disease. (orig.)

  19. Gene expression analysis of induced pluripotent stem cells from aneuploid chromosomal syndromes

    Science.gov (United States)

    2013-01-01

    Background Human aneuploidy is the leading cause of early pregnancy loss, mental retardation, and multiple congenital anomalies. Due to the high mortality associated with aneuploidy, the pathophysiological mechanisms of aneuploidy syndrome remain largely unknown. Previous studies focused mostly on whether dosage compensation occurs, and the next generation transcriptomics sequencing technology RNA-seq is expected to eventually uncover the mechanisms of gene expression regulation and the related pathological phenotypes in human aneuploidy. Results Using next generation transcriptomics sequencing technology RNA-seq, we profiled the transcriptomes of four human aneuploid induced pluripotent stem cell (iPSC) lines generated from monosomy × (Turner syndrome), trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome), and partial trisomy 11:22 (Emanuel syndrome) as well as two umbilical cord matrix iPSC lines as euploid controls to examine how phenotypic abnormalities develop with aberrant karyotype. A total of 466 M (50-bp) reads were obtained from the six iPSC lines, and over 13,000 mRNAs were identified by gene annotation. Global analysis of gene expression profiles and functional analysis of differentially expressed (DE) genes were implemented. Over 5000 DE genes are determined between aneuploidy and euploid iPSCs respectively while 9 KEGG pathways are overlapped enriched in four aneuploidy samples. Conclusions Our results demonstrate that the extra or missing chromosome has extensive effects on the whole transcriptome. Functional analysis of differentially expressed genes reveals that the genes most affected in aneuploid individuals are related to central nervous system development and tumorigenesis. PMID:24564826

  20. Atypical progeroid syndrome: An unknown helicase gene defect?

    NARCIS (Netherlands)

    Ruijs, M. W. G.; van Andel, R. N. J.; Oshima, J.; Madan, K.; Nieuwint, A. W. M.; Aalfs, C. M.

    2003-01-01

    We describe a boy with chromosomal breakage syndrome, who died of hepatocellular carcinoma at the age of 17 years. Other findings included growth retardation, bilateral cataracts, premature graying of hair and elevated levels of urinary hyaluronic acid. Intellectual functions were normal. Although

  1. Restless Legs Syndrome/Willis-Ekbom Disease and Pregnancy.

    Science.gov (United States)

    Prosperetti, Chiara; Manconi, Mauro

    2015-09-01

    Restless legs syndrome (RLS)/Willis-Ekbom disease is 3-fold more prevalent in pregnant than in non-pregnant women. Symptoms are particularly strong and frequent during the third trimester of pregnancy and disappear around delivery. A pre-existing form of RLS tends to worsen during pregnancy. Women who experience RLS during pregnancy have a higher risk of symptoms in further pregnancies and of developing a primary form of RLS later in life, than women free of symptoms during pregnancy. This article reviews the literature for pregnancy-related RLS, with particular attention to its epidemiology, course, possible mechanisms, management, and the impact of symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Study on the correlation between KCNJ11 gene polymorphism and metabolic syndrome in the elderly.

    Science.gov (United States)

    Jiang, Fan; Liu, Ning; Chen, Xiao Zhuang; Han, Kun Yuan; Zhu, Cai Zhong

    2017-09-01

    The aim of the study was to examine the correlation between KCNJ11 gene polymorphism and metabolic syndrome in elderly patients. From January 2014 to January 2015, 54 elderly patients with metabolic syndrome were enrolled in this study as the observation group. During the same period, 46 healthy elderly individuals were enrolled in this study as the control group. KCNJ11 gene polymorphism (rs28502) was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The expression levels of mRNA in different genotypes were detected using FQ-PCR. ELISA was used to evaluate the KCNJ11 protein expression in different genotypes. KCNJ11 gene polymorphism and metabolic syndrome was studied by measuring the blood pressure levels in patients with different genotypes. Three genotypes of KCNJ11 gene in rs28502 were CC, CT and TT. The CC, CT and TT genotype frequencies in healthy population were 8.5, 9.2 and 82.2%, respectively, while the genotype frequencies in patients with metabolic syndrome were 42.4, 49.8 and 7.8%, respectively. There were significant differences between groups (P≤0.05). However, the genotype frequencies of C/T in healthy individuals and metabolic syndrome patients were 35.3 and 38.3%, respectively. There were no significant differences between groups (P>0.05). FQ-PCR results showed that the KCNJ11 mRNA expression levels in the control and observation groups had no significant differences (P>0.05). However, the results obtained from ELISA analysis revealed that KCNJ11 protein expression level in the observation group was significantly higher than that in the control group (Pmetabolic syndrome in the elderly. Elderly patients with the CC and TT genotypes are more likely to develop metabolic syndrome.

  3. Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children.

    Science.gov (United States)

    Dhandapani, Mohanapriya Chinambedu; Venkatesan, Vettriselvi; Rengaswamy, Nammalwar Bollam; Gowrishankar, Kalpana; Ekambaram, Sudha; Sengutavan, Prabha; Perumal, Venkatachalam

    2017-02-01

    Steroid-resistant nephrotic syndrome (SRNS) is found in 10-20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India. Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy-Weinberg equilibrium. Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708). Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children's at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk.

  4. A novel nonsense mutation in the WFS1 gene causes the Wolfram syndrome.

    Science.gov (United States)

    Noorian, Shahab; Savad, Shahram; Mohammadi, Davood Shah

    2016-05-01

    Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder, which is mostly caused by mutations in the WFS1 gene. The WFS1 gene product, which is called wolframin, is thought to regulate the function of endoplasmic reticulum. The endoplasmic reticulum has a critical role in protein folding and material transportation within the cell or to the surface of the cell. Identification of new mutations in WFS1 gene will unravel the molecular pathology of WS. The aim of this case report study is to describe a novel mutation in exon 4 of the WFS1 gene (c.330C>A) in a 9-year-old boy with WS.

  5. Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Karina Banasik

    2011-01-01

    Full Text Available Candidate genes for non-alcoholic fatty liver disease (NAFLD identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D, central obesity, and WHO-defined metabolic syndrome (MetS.273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05 to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.

  6. 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.

  7. Prioritisation and network analysis of Crohn's disease susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Daniele Muraro

    Full Text Available Recent Genome-Wide Association Studies (GWAS have revealed numerous Crohn's disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn's susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC. Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn's patients intestinal tissue in comparison with healthy donors.

  8. Dopamine dysregulation syndrome in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    A V Nikitina

    2013-01-01

    Full Text Available Dopamine dysregulation syndrome (DDS is an iatrogenic disease developing during dopaminergic therapy. According to the data available in the literature, DDS develops in 3-4% of the Parkinson’s disease (PD cases. DDS in PD is frequently accompanied by other impulse control disorders (ICD: punding, compulsive shopping, hypersexuality, overeating. 246 patients with PD, of whom 16 (6.4% were found to have DDS, were examined. The patients’ age was 64±7.4 years. Women (n = 10 more often developed DDS than men (n = 6. The patients mainly suffered from the mixed form of the disease. Stages III and IV were diagnosed in 72 and 22%, respectively. The duration of PD was 12+2.6 years. In the PD patients with DDS, the quality-of-life indicators ranged from 19.8 to 90% (54+20.1%. The equivalent dose of levodopa is 1323.4+299 mg/day. DDS was concurrent with other types of ICD in 4 patients: panding in 2, compulsive shopping and punding in 1, and punding and hypersexuality. The doses of levodopa were corrected in patients receiving high doses of dopaminergic drugs. In the patients with DDS concurrent with punding or hypersexuality, the dose of dopaminergic receptor agonists was gradually reduced and subsequently discontinued.

  9. Prevalence of chronic kidney disease in adults with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    P C Emem-Chioma

    2011-01-01

    Full Text Available The burden of chronic kidney disease (CKD and other non- communicable diseases continues to rise globally, and recent studies suggest that metabolic syndrome (MS may add to this burden by contributing to the development of CKD. Given that reports on the prevalence of CKD in patients with MS in this environment are scanty, this study was undertaken with the sole aim of determining the prevalence of CKD in subjects with MS as defined by the International Diabetes Federation (IDF and the National Cholesterol Education Project Adult Treatment Panel III (NCEP ATP III. A total of 240 consenting adults (18-70 years attending the general out- patient clinic of the General Hospital Okrika for various ailments were studied. Subjects were screened for MS as per the above- mentioned criteria. Estimated GFR (eGFR was determined with Modification of Diet for Renal Disease (MDRD formula and CKD was defined as eGFR less than 60 mL/min/1.73 m2 . Data was analyzed using SPSS version 12.0 and Epi info version 4.06d; P 0.05. CKD was more common in subjects with MS compared with those without, although the difference was not statistically significant. The prevalence of CKD in subjects with MS in our study population did not differ significantly when the different MS definitions were employed.

  10. Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.

    Science.gov (United States)

    de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

    2016-10-06

    Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1 +/- mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

  11. Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic Syndrome.

    Science.gov (United States)

    Goicoechea de Jorge, Elena; Tortajada, Agustín; García, Sheila Pinto; Gastoldi, Sara; Merinero, Héctor Martín; García-Fernández, Jesús; Arjona, Emilia; Cao, Mercedes; Remuzzi, Giuseppe; Noris, Marina; Rodríguez de Córdoba, Santiago

    2018-01-01

    Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort ( n =513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene ( CFHR1 ) that originates by recurrent gene conversion events between the CFH and CFHR1 genes. The novel CFHR1 mutants encode an FHR-1 protein with two amino acid substitutions, L290S and A296V, converting the FHR-1 C terminus into that of factor H (FH). Next-generation massive-parallel DNA sequencing (NGS) analysis did not detect these genetic abnormalities. In addition to the CFHR1 mutant, six patients carried the previously uncharacterized CFH-411T variant. In functional analyses, the mutant FHR-1 protein strongly competed the binding of FH to cell surfaces, impairing complement regulation, whereas the CFH-411T polymorphism lacked functional consequences. Carriers of the CFHR1 mutation presented with severe aHUS during adulthood; 57% of affected women in this cohort presented during the postpartum period. Analyses in patients and unaffected carriers showed that FH plasma levels determined by the nonmutated chromosome modulate disease penetrance. Crucially, in the activated endothelial (HMEC-1) cell assay, reduced FH plasma levels produced by the nonmutated chromosome correlated inversely with impairment of complement regulation, measured as C5b-9 deposition. Our data advance understanding of the genetic complexities underlying aHUS, illustrate the importance of performing functional analysis, and support the use of complementary assays to disclose genetic abnormalities not revealed by current NGS analysis. Copyright © 2018 by the American Society of Nephrology.

  12. Molecular detection of disease resistance genes to powdery mildew ...

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    2017-01-04

    Jan 4, 2017 ... 2. State Key Laboratory of Biology for Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of. Agricultural Sciences, Beijing 100193, China. Received 10 October, 2016; Accepted 14 December, 2016. A study was conducted to detect the presence of disease resistance genes to ...

  13. The Role of Nuclear Bodies in Gene Expression and Disease

    Science.gov (United States)

    Morimoto, Marie; Boerkoel, Cornelius F.

    2013-01-01

    This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. PMID:24040563

  14. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases.

    Science.gov (United States)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-01-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  15. [Sebaceous gland tumor with a rare gene mutation within a tumor syndrome: Muir-Torre syndrome].

    Science.gov (United States)

    Voigt, E; Sommer, F; Geiger, K D; Pillunat, L E

    2014-04-01

    Muir-Torre syndrome is a rare autosomal dominant subtype of hereditary nonpolyposis colorectal carcinoma and is characterized by the simultaneous occurrence of sebaceous gland neoplasms with visceral and urogenital malignancies. This article describes the case of a 72-year-old patient who was referred to our clinic for removal of an upper eyelid tumor, showing the course from the clinical findings to the rare diagnosis of Muir-Torre syndrome.

  16. Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

    Science.gov (United States)

    Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

    2017-09-01

    The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

  17. Crohn’s Disease: a Role of Gut Microbiota and Nod2 Gene Polymorphisms in Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Lucia Hrnčířová

    2014-01-01

    Full Text Available Crohn’s disease is a chronic immune-mediated intestinal inflammation targeted against a yet incompletely defined subset of commensal gut microbiota and occurs on the background of a genetic predisposition under the influence of environmental factors. Genome-wide association studies have identified about 70 genetic risk loci associated with Crohn’s disease. The greatest risk for Crohn’s disease represent polymorphisms affecting the CARD15 gene encoding nucleotide-binding oligomerization domain 2 (NOD2 which is an intracellular sensor for muramyl dipeptide, a peptidoglycan constituent of bacterial cell wall. The accumulated evidence suggests that gut microbiota represent an essential, perhaps a central factor in the induction and maintaining of Crohn’s disease where dysregulation of normal co-evolved homeostatic relationships between intestinal microbiota and host mucosal immune system leads to intestinal inflammation. Taken together, these findings identify Crohn’s disease as a syndrome of overlapping phenotypes that involves variable influences of genetic and environmental factors. A deeper understanding of different genetic abnormalities underlying Crohn’s disease together with the identification of beneficial and harmful components of gut microbiota and their interactions are essential conditions for the categorization of Crohn’s disease patients, which enable us to design more effective, preferably causative, individually tailored therapy.

  18. Gene-disease relationship discovery based on model-driven data integration and database view definition.

    Science.gov (United States)

    Yilmaz, S; Jonveaux, P; Bicep, C; Pierron, L; Smaïl-Tabbone, M; Devignes, M D

    2009-01-15

    Computational methods are widely used to discover gene-disease relationships hidden in vast masses of available genomic and post-genomic data. In most current methods, a similarity measure is calculated between gene annotations and known disease genes or disease descriptions. However, more explicit gene-disease relationships are required for better insights into the molecular bases of diseases, especially for complex multi-gene diseases. Explicit relationships between genes and diseases are formulated as candidate gene definitions that may include intermediary genes, e.g. orthologous or interacting genes. These definitions guide data modelling in our database approach for gene-disease relationship discovery and are expressed as views which ultimately lead to the retrieval of documented sets of candidate genes. A system called ACGR (Approach for Candidate Gene Retrieval) has been implemented and tested with three case studies including a rare orphan gene disease.

  19. Pathophysiological, genetic and gene expression features of a novel rodent model of the cardio-metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Robert H Wallis

    2008-08-01

    Full Text Available Complex etiology and pathogenesis of pathophysiological components of the cardio-metabolic syndrome have been demonstrated in humans and animal models.We have generated extensive physiological, genetic and genome-wide gene expression profiles in a congenic strain of the spontaneously diabetic Goto-Kakizaki (GK rat containing a large region (110 cM, 170 Mb of rat chromosome 1 (RNO1, which covers diabetes and obesity quantitative trait loci (QTL, introgressed onto the genetic background of the normoglycaemic Brown Norway (BN strain. This novel disease model, which by the length of the congenic region closely mirrors the situation of a chromosome substitution strain, exhibits a wide range of abnormalities directly relevant to components of the cardio-metabolic syndrome and diabetes complications, including hyperglycaemia, hyperinsulinaemia, enhanced insulin secretion both in vivo and in vitro, insulin resistance, hypertriglyceridemia and altered pancreatic and renal histological structures. Gene transcription data in kidney, liver, skeletal muscle and white adipose tissue indicate that a disproportionately high number (43-83% of genes differentially expressed between congenic and BN rats map to the GK genomic interval targeted in the congenic strain, which represents less than 5% of the total length of the rat genome. Genotype analysis of single nucleotide polymorphisms (SNPs in strains genetically related to the GK highlights clusters of conserved and strain-specific variants in RNO1 that can assist the identification of naturally occurring variants isolated in diabetic and hypertensive strains when different phenotype selection procedures were applied.Our results emphasize the importance of rat congenic models for defining the impact of genetic variants in well-characterised QTL regions on in vivo pathophysiological features and cis-/trans- regulation of gene expression. The congenic strain reported here provides a novel and sustainable model for

  20. Vascular risk factors, cardiovascular disease and restless legs syndrome in men

    Science.gov (United States)

    Winter, Anke C.; Berger, Klaus; Glynn, Robert J; Buring, Julie E.; Gaziano, J. Michael; Schürks, Markus; Kurth, Tobias

    2012-01-01

    Background Prevalences of vascular risk factors, cardiovascular disease and restless legs syndrome increase with age. Prior studies analyzing the associations between vascular risk factors, cardiovascular disease, and restless legs syndrome found controversial results. We therefore aim to evaluate the association between prevalent vascular risk factors, prevalent cardiovascular disease and restless legs syndrome. Methods We conducted a cross-sectional study among 22,786 participants of the US Physicians’ Health Studies I and II. Restless legs syndrome was classified according to the four minimal diagnostic criteria. Vascular risk factors and restless legs syndrome symptoms were self-reported. Prevalent cardiovascular disease events including major cardiovascular disease, stroke and myocardial infarction were confirmed by medical record review. Age- and multivariable-adjusted logistic regression models were used to evaluate the association between vascular risk factors, prevalent cardiovascular disease events and restless legs syndrome. Results The mean age of the cohort 67.8 years. Restless legs syndrome prevalence was 7.5% and increased significantly with age. Diabetes significantly increased the odds (OR: 1.41, 95%CI: 1.21–1.65), while frequent exercise (OR: 0.78, 95%CI: 0.67–0.91) and alcohol consumption of one or more drinks per day (OR: 0.80, 95%CI: 0.69–0.92) significantly reduced the odds of restless legs syndrome in multivariable-adjusted models. Prevalent stroke showed an increased multivariable-adjusted OR of 1.40 (1.05–1.86) while men with prevalent myocardial infarction had a decreased OR of 0.73 (0.55–0.97) for restless legs syndrome. Conclusions The restless legs syndrome prevalence among US male physicians is similar to men of the same age group in other western countries. A history of diabetes is the most consistent risk factor associated with restless legs syndrome. Prevalent stroke and myocardial infarction are related to restless legs

  1. Disease: H00469 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available of disorders, and many disease genes are still unidentified. However, the disease mechanisms seem to be int...chondrial DNA depletion syndromes--many genes, common mechanisms. ... JOURNAL ... Neu

  2. Collectrin gene screening in Turner syndrome patients with kidney ...

    Indian Academy of Sciences (India)

    immune basis, suggesting that hap- loinsufficiency for X-chromosome gene(s) impairs beta-cell function predisposing to diabetes mellitus in TS (Bakalov et al. 2004). The loss of the short arm of chromosome X (Xp), common to all TS, generally ...

  3. Gene expression of transcription factor NFATc1 in periodontal diseases

    OpenAIRE

    Belibasakis, G N; Emingil, G; Saygan, B; Turkoglu, O; Atilla, G; Bostanci, N

    2011-01-01

    Belibasakis GN, Emingil G, Saygan B, Turkoglu O, Atilla G, Bostanci N. Gene expression of transcription factor NFATc1 in periodontal diseases. APMIS 2011; 119: 167-172. Periodontitis is a disease of infectious aetiology that causes inflammatory destruction of the tooth-supporting tissues. Activated T cells are central to the pathogenesis of the disease, by producing receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) that stimulates bone resorption. Antigenic activation of T cells ...

  4. Sandhoff Disease without Hepatosplenomegaly Due to Hexosaminidase B Gene Mutation

    OpenAIRE

    Gowda, Vykuntaraju K.; Amoghimath, Raghavendraswami; Srinivasan, Varun M.; Bhat, Maya

    2017-01-01

    Sandhoff disease is a neurodegenerative disease caused due to deficiency of hexosaminidase (HEX) A and B. A 1-year-old male child presented with regression of milestones, exaggerated startle response, decreased vision, and seizures from 6 months of age. The child had coarse facies without hepatosplenomegaly. Serum levels of β hexosaminidase total (A + B) were low. Genetic testing for Sandhoff disease revealed a homozygous missense variant on HEXB gene. The case is presented to highlight that ...

  5. Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA......) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...... immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes....

  6. Fanconi syndrome

    Science.gov (United States)

    De Toni-Fanconi syndrome ... Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown. Common causes of Fanconi syndrome in ...

  7. Gene Expression Factor Analysis to Differentiate Pathways Linked to Fibromyalgia, Chronic Fatigue Syndrome, and Depression in a Diverse Patient Sample.

    Science.gov (United States)

    Iacob, Eli; Light, Alan R; Donaldson, Gary W; Okifuji, Akiko; Hughen, Ronald W; White, Andrea T; Light, Kathleen C

    2016-01-01

    To determine if independent candidate genes can be grouped into meaningful biologic factors, and whether these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS), while controlling for comorbid depression, sex, and age. We included leukocyte messenger RNA gene expression from a total of 261 individuals, including healthy controls (n = 61), patients with FMS only (n = 15), with CFS only (n = 33), with comorbid CFS and FMS (n = 79), and with medication-resistant (n = 42) or medication-responsive (n = 31) depression. We used exploratory factor analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine whether these factors were associated with specific diagnoses. EFA resulted in 4 independent factors with minimal overlap of genes between factors, explaining 51% of the variance. We labeled these factors by function as 1) purinergic and cellular modulators, 2) neuronal growth and immune function, 3) nociception and stress mediators, and 4) energy and mitochondrial function. Regression analysis predicting these biologic factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (Quick Inventory for Depression Symptomatology score), but not associated with FMS. Expression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters, but in opposite directions, when controlling for comorbid FMS. Given high comorbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression. © 2016, American College of Rheumatology.

  8. Impact of gene patents and licensing practices on access to genetic testing for long QT syndrome.

    Science.gov (United States)

    Angrist, Misha; Chandrasekharan, Subhashini; Heaney, Christopher; Cook-Deegan, Robert

    2010-04-01

    Genetic testing for long QT syndrome exemplifies patenting and exclusive licensing with different outcomes at different times. Exclusive licensing from the University of Utah changed the business model from sole provider to two US providers of long QT syndrome testing. Long QT syndrome is associated with mutations in many genes, 12 of which are now tested by two competing firms in the United States, PGxHealth and GeneDx. Until 2009, PGxHealth was the sole provider, based largely on exclusive rights to patents from the University of Utah and elsewhere. University of Utah patents were initially licensed to DNA Sciences, whose patent rights were acquired by Genaissance, and then by Clinical Data, Inc., which owns PGxHealth. In 2002, DNA Sciences, Inc., "cleared the market" by sending cease-and-desist patent enforcement letters to university and reference laboratories offering long QT syndrome genetic testing. There was no test on the market for a 1- to 2-year period. From 2005-2008, most long QT syndrome-related patents were controlled by Clinical Data, Inc., and its subsidiary PGxHealth. Bio-Reference Laboratories, Inc., secured countervailing exclusive patent rights starting in 2006, also from the University of Utah, and broke the PGxHealth monopoly in early 2009, creating a duopoly for genetic testing in the United States and expanding the number of genes for which commercial testing is available from 5 to 12.

  9. Treacher Collins Syndrome with a de Novo 5-bp Deletion in the TCOF1 Gene

    OpenAIRE

    Su, Pen-Hua; Chen, Jia-Yu; Chen, Suh-Jen; Yu, Ju-Shan

    2006-01-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development with features including malar hypoplasia, micrognathia, microtia, downward slanting palpebral fissures, lower eyelid coloboma, conductive hearing loss, and cleft palate. TCS is caused by mutations in the TCOF1 gene, which encodes the nuclear phosphoprotein treacle. Here, we describe a 1-day-old male infant with classical TCS presentation. A 5-bp deletion in exon 22 of the TCOF1 gene (3469del ACTCT) w...

  10. Microdeletion syndromes disclose replication timing alterations of genes unrelated to the missing DNA

    Directory of Open Access Journals (Sweden)

    Freedman Jane

    2009-03-01

    Full Text Available Abstract Background The temporal order of allelic replication is interrelated to the epigenomic profile. A significant epigenetic marker is the asynchronous replication of monoallelically-expressed genes versus the synchronous replication of biallelically-expressed genes. The present study sought to determine whether a microdeletion in the genome affects epigenetic profiles of genes unrelated to the missing segment. In order to test this hypothesis, we checked the replication patterns of two genes – SNRPN, a normally monoallelically expressed gene (assigned to 15q11.13, and the RB1, an archetypic biallelically expressed gene (assigned to 13.q14 in the genomes of patients carrying the 22q11.2 deletion (DiGeorge/Velocardiofacial syndrome and those carrying the 7q11.23 deletion (Williams syndrome. Results The allelic replication timing was determined by fluorescence in situ hybridization (FISH technology performed on peripheral blood cells. As expected, in the cells of normal subjects the frequency of cells showing asynchronous replication for SNRPN was significantly (P -12 higher than the corresponding value for RB1. In contrast, cells of the deletion-carrying patients exhibited a reversal in this replication pattern: there was a significantly lower frequency of cells engaging in asynchronous replication for SNRPN than for RB1 (P -4 and P -3 for DiGeorge/Velocardiofacial and Williams syndromes, respectively. Accordingly, the significantly lower frequency of cells showing asynchronous replication for SNRPN than for RB1 is a new epigenetic marker distinguishing these deletion syndrome genotypes from normal ones. Conclusion In cell samples of each deletion-carrying individual, an aberrant, reversed pattern of replication is delineated, namely, where a monoallelic gene replicates more synchronously than a biallelic gene. This inverted pattern, which appears to be non-deletion-specific, clearly distinguishes cells of deletion-carriers from normal

  11. Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease

    OpenAIRE

    Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter Alan; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L.; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A.; Naj, Adam C.; Sims, Rebecca

    2014-01-01

    PUBLISHED BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over...

  12. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome.

    Science.gov (United States)

    Light, A R; Bateman, L; Jo, D; Hughen, R W; Vanhaitsma, T A; White, A T; Light, K C

    2012-01-01

    To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise. Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments. No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor's and one cytokine gene's transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor's transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.   At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for

  13. Restless Leg Syndrome Across the Globe: Epidemiology of the Restless Legs Syndrome/Willis-Ekbom Disease.

    Science.gov (United States)

    Koo, Brian B

    2015-09-01

    There are more than 50 epidemiologic studies measuring the prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) across 5 of the 6 inhabited continents (not Australia), most conducted in North America and Europe. Sufficient studies have been conducted in Asia, North America, and Europe to make inferences on RLS/WED prevalence by region. RLS/WED prevalence is thought to be highest in North America and Europe and lower in Asia. These differences across regions may be explained by cultural, environmental, and genetic factors. Future investigation is needed to determine to what extent these factors affect expression of RLS/WED according to world region. Published by Elsevier Inc.

  14. Restless Legs Syndrome and Its Associated Risk Factors in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Shahrul Azmin

    2013-01-01

    Full Text Available Introduction. Restless legs syndrome has been shown to negatively impact the quality of life of patients. Studies have shown an association between restless legs syndrome and Parkinson’s disease. We attempted to investigate the prevalence of restless legs syndrome in Parkinson’s disease patients and to identify associated risk factors. Method. This was a cross-sectional study among patients with idiopathic Parkinson’s disease. Exclusion criterion was a Mini Mental State Examination score of less than 21/30. The International Restless Legs Syndrome Study Group criterion was used to identify patients with restless legs syndrome. Results. A total of 113 patients were recruited. The prevalence rate of restless legs syndrome in our cohort was 9.7% and was significantly associated with a younger onset of Parkinson’s disease (P=0.023, male gender (P=0.045, higher Mini Mental State Examination score (P=0.004, and less advanced Hoehn & Yahr stage (P=0.014. Conclusion. The prevalence rate of restless legs syndrome in our Parkinson’s disease population is in keeping with other studies published worldwide. The significance of the association between a younger onset of Parkinson’s disease and restless legs syndrome needs to be further investigated.

  15. Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke.

    Science.gov (United States)

    Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A

    2014-01-01

    Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Restless legs syndrome and its associated risk factors in Parkinson's disease.

    Science.gov (United States)

    Azmin, Shahrul; Khairul Anuar, Abdul Manaf; Nafisah, Wan Yahya; Tan, Hui Jan; Raymond, Azman Ali; Hanita, Othman; Shah, Shamsul Azhar; Norlinah, Mohamed Ibrahim

    2013-01-01

    Introduction. Restless legs syndrome has been shown to negatively impact the quality of life of patients. Studies have shown an association between restless legs syndrome and Parkinson's disease. We attempted to investigate the prevalence of restless legs syndrome in Parkinson's disease patients and to identify associated risk factors. Method. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criterion was a Mini Mental State Examination score of less than 21/30. The International Restless Legs Syndrome Study Group criterion was used to identify patients with restless legs syndrome. Results. A total of 113 patients were recruited. The prevalence rate of restless legs syndrome in our cohort was 9.7% and was significantly associated with a younger onset of Parkinson's disease (P = 0.023), male gender (P = 0.045), higher Mini Mental State Examination score (P = 0.004), and less advanced Hoehn & Yahr stage (P = 0.014). Conclusion. The prevalence rate of restless legs syndrome in our Parkinson's disease population is in keeping with other studies published worldwide. The significance of the association between a younger onset of Parkinson's disease and restless legs syndrome needs to be further investigated.

  17. Do the MTHFR gene polymorphism and Down syndrome pregnancy ...

    African Journals Online (AJOL)

    Srinivasan Muthuswamy

    2015-09-28

    Sep 28, 2015 ... Abstract Background: Down syndrome, the most common trisomy 21 arises from abnormal .... chromosomal segregation, predisposing to trisomy 21 [2]. .... 94. 73 18. 0.49. 51 48. 6. 101. 73. 9. 0.36. Indian studies. Cyril [11]. India. 36/60. 33. 3. 0. 60. 0. 0. 0. 14 19. 3. 26. 21 13. 0.03. Kaur [13]. India. 110/111.

  18. Cauda equina syndrome: an uncommon symptom of aortic diseases.

    Science.gov (United States)

    He, Fuliang; Xing, Tong; Yu, Fang; Li, Hongchuan; Fang, Xiutong; Song, Hongxing

    2015-01-01

    In order to help diagnose and deal with the fetal aortic diseases in time, we retrospectively reviewed 8 patients who presented with cauda equina syndrome (CES) but actually suffered from low spinal nerve ischemia due to aortic diseases. 8 patients were initially diagnosed as CES. 7 patients were confirmed with aortic diseases. 1 patient was confirmed with aortic saddle embolism post emergent laminectomy. Relief of CES symptoms was evaluated during preoperation and follow-up period. 1 patient was diagnosed as aortic dissection and 5 patients as AAA. These 6 patients underwent endovascular aortic repair (EVAR). The CES was relieved in 5-10 d post procedure. The 7th patient was diagnosed with acute abdominal aortic occlusion and then underwent catheter directed thrombolysis with recombinant tissue plasminogen activator (rTPA) for 20 h and CES disappeared. The JOA scores of the 7 patients were recovered from preoperative 15.14±1.21 to 21.00±2.16 within 5-10 d (P<0.01), and evaluated to be 24.12±1.34, 25.88±1.21 and 26.29±1.11 at 3 m-, 6 m- and 12 m-follow-up point, respectively. The 8th patient was initially diagnosed as lumbar spinal stenosis and lumbar disc herniation. The patient underwent emergent vertebral canal decompression and presented with serious CES symptoms. CTA confirmed that the patient had been suffered from aortic saddle embolism (ASE). CES caused by abdominal aortic diseases is a special event with fetal consequences if it is not recognized and treated promptly. Orthopedists and neurosurgeons should pay attentions particularly to this issue to preserve the cauda equina functions to their maximums.

  19. A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

    Science.gov (United States)

    Salehi, Nooshin; Choi, Eric D; Garrison, Roger C

    2017-01-16

    BACKGROUND Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1-5% of all Guillain-Barre cases in Western countries. Patients with Miller Fisher Syndrome usually have good recovery without residual deficits. Venous thromboembolism is a common complication of Guillain-Barre Syndrome and has also been reported in Miller Fisher Syndrome, but it has generally been reported in the presence of at least one prothrombotic risk factor such as immobility. A direct correlation between venous thromboembolism and Miller Fisher Syndrome or Guillain-Barre Syndrome has not been previously described. CASE REPORT We report the case of a 32-year-old Hispanic male who presented with acute, severe thromboembolic disease and concurrently demonstrated characteristic clinical features of Miller Fisher Syndrome including ophthalmoplegia, ataxia, and areflexia. Past medical and family history were negative for thromboembolic disease, and subsequent hypercoagulability workup was unremarkable. During the course of hospitalization, the patient also developed angioedema. CONCLUSIONS We describe a possible association between Miller Fisher Syndrome, thromboembolic disease, and angioedema.

  20. Neuronal plasticity and astrocytic reaction in Down syndrome and Alzheimer disease

    DEFF Research Database (Denmark)

    Jørgensen, Ole Steen; Brooksbank, B W; Balázs, R

    1990-01-01

    disease (AD) and adults with Down syndrome (DS), the latter also presenting manifest signs of Alzheimer type of neuropathology. The trend of changes was similar in AD and DS, but more marked in the latter. The biochemical make-up of astrocytes was differentially affected: in both the frontal and DS...... were about 180% and 230% of control. The observations (normal GS and elevated levels of the other markers) might suggest that the pathological changes involve a differentiated astrocytic reaction and that the astrocytic reaction is more marked in DS than in AD. In DS the increase in S100 could...... be explained, in part, by a gene dosage effect and in part by reactive gliosis. The neuronal markers were also differentially affected. In comparison with appropriate controls, the concentration of D3-protein in frontal cortex was decreased by 24% in DS and by 14% in AD, whereas NCAM levels were...

  1. The first missense mutation of NHS gene in a Tunisian family with clinical features of NHS syndrome including cardiac anomaly.

    Science.gov (United States)

    Chograni, Manèl; Rejeb, Imen; Jemaa, Lamia Ben; Châabouni, Myriam; Bouhamed, Habiba Chaabouni

    2011-08-01

    Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome is a disease of unknown gene action mechanism, characterized by congenital cataract, dental anomalies, dysmorphic features and, in some cases, mental retardation. We performed linkage analysis in a Tunisian family with NHS in which affected males and obligate carrier female share a common haplotype in the Xp22.32-p11.21 region that contains the NHS gene. Direct sequencing of NHS coding exons and flanking intronic sequences allowed us to identify the first missense mutation (P551S) and a reported SNP-polymorphism (L1319F) in exon 6, a reported UTR-SNP (c.7422 C>T) and a novel one (c.8239 T>A) in exon 8. Both variations P551S and c.8239 T>A segregate with NHS phenotype in this family. Although truncations, frame-shift and copy number variants have been reported in this gene, no missense mutations have been found to segregate previously. This is the first report of a missense NHS mutation causing NHS phenotype (including cardiac defects). We hypothesize also that the non-reported UTR-SNP of the exon 8 (3'-UTR) is specific to the Tunisian population.

  2. Prioritizing causal disease genes using unbiased genomic features.

    Science.gov (United States)

    Deo, Rahul C; Musso, Gabriel; Tasan, Murat; Tang, Paul; Poon, Annie; Yuan, Christiana; Felix, Janine F; Vasan, Ramachandran S; Beroukhim, Rameen; De Marco, Teresa; Kwok, Pui-Yan; MacRae, Calum A; Roth, Frederick P

    2014-12-03

    Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits. To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM. Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature.

  3. Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

    2014-01-01

    Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...... with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic...... for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic...

  4. A Novel Fibrillin-1 Gene Mutation Leading to Marfan Syndrome in a Korean Girl.

    Science.gov (United States)

    Nam, Hyo-Kyoung; Nam, Myung-Hyun; Ha, Kee-Soo; Rhie, Young-Jun; Lee, Kee-Hyoung

    2017-03-01

    Marfan syndrome is an autosomal dominant genetic disorder caused by a connective tissue defect. A nine-year-old girl was referred to our pediatric endocrinology clinic for tall stature. Physical examination revealed a lens dislocation with strabismus, high palate, positive wrist and thumb signs, joint hypermobility, and pes planus. Transthoracic echocardiography revealed dilatation of the aortic root. She was diagnosed with Marfan syndrome based on the revised Ghent diagnostic criteria. Molecular investigation identified a heterozygous c.2810G >A variation in the FBN1 gene in the patient, but not in her parents. To our knowledge, this sequence variant has been reported as a polymorphism (rs113602180), but it is the first report identifying it as the genetic cause of Marfan syndrome. We hypothesize that this de novo novel missense FBN1 mutation disrupts fibrillin-1 function and is probably involved in the development of Marfan syndrome in this patient. © 2017 by the Association of Clinical Scientists, Inc.

  5. Association of restless legs syndrome, pain, and mood disorders in Parkinson's disease.

    Science.gov (United States)

    Rana, Abdul Qayyum; Qureshi, Abdul Rehman M; Rahman, Labiba; Jesudasan, Ajantha; Hafez, Kevin K; Rana, Mohammad A

    2016-01-01

    The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients' comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.

  6. Association of arginine vasopressin receptor 1a gene polymorphisms with hepatorenal syndrome

    International Nuclear Information System (INIS)

    Wang, C.; Luo, X.; Ye, J.; Liu, S.; Miu, L.; Bao, J.; Wang, F.; Yu, Z.

    2017-01-01

    To assess the association of arginine vasopressin receptor 1a gene single nucleotide polymorphisms with type I hepatorenal syndrome. Methods: The case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou, China, from January 2012 to June 2014, and comprised patients with type I hepatorenal syndrome and individuals with cirrhosis who acted as the control group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide polymorphisms were analysed by high-resolution melting methods. Statistical analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%) were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age was 42.21+-11.30years in the hepatorenal syndrome group and 43.69+-12.60 in the control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity levels were 154.76+-51.58, 49.30+-24.67 and 33.42+-3.69 in the hepatorenal syndrome group compared to 181.26+-64.46, 41.78+-17.52 and 32.98+-4.81 among controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were found in the distributions of arginine vasopressin receptor 1a gene rs113481894 locus T allele between type I hepatorenal syndrome patients and the control group (odds ratio= 2.230; p= 0.040). Conclusion: T allele located at arginine vasopressin receptor 1a receptor promoter rs113481894 locus may be associated with the pathogenesis of type I hepatorenal syndrome. (author)

  7. Catecholamine-related gene expression in blood correlates with tic severity in tourette syndrome

    NARCIS (Netherlands)

    Gunther, Joan; Tian, Yingfang; Stamova, Boryana; Lit, Lisa; Corbett, Blythe; Ander, Brad; Zhan, Xinhua; Jickling, Glen; Bos-Veneman, Netty; Liu, Da; Hoekstra, Pieter; Sharp, Frank

    2012-01-01

    Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS

  8. The Brugada Syndrome Susceptibility Gene HEY2 Modulates Cardiac Transmural Ion Channel Patterning and Electrical Heterogeneity

    NARCIS (Netherlands)

    Veerman, Christiaan C.; Podliesna, Svitlana; Tadros, Rafik; Lodder, Elisabeth M.; Mengarelli, Isabella; de Jonge, Berend; Beekman, Leander; Barc, Julien; Wilders, Ronald; Wilde, Arthur A.; Boukens, Bastiaan J.; Coronel, Ruben; Verkerk, Arie; Remme, Carol Ann; Bezzina, Connie R.

    2017-01-01

    Genome-wide association studies previously identified an association of rs9388451 at chromosome 6q22.3 (near HEY2) with Brugada syndrome. The causal gene and underlying mechanism remain unresolved. We used an integrative approach entailing transcriptomic studies in human hearts and

  9. Gene, Brain, and Behavior Relationships in Fragile X Syndrome: Evidence from Neuroimaging Studies

    Science.gov (United States)

    Lightbody, Amy A.; Reiss, Allan L.

    2009-01-01

    Fragile X syndrome (FraX) remains the most common inherited cause of intellectual disability and provides a valuable model for studying gene-brain-behavior relationships. Over the past 15 years, structural and functional magnetic resonance imaging studies have emerged with the goal of better understanding the neural pathways contributing to the…

  10. Correlations of gene expression with ratings of inattention and hyperactivity/impulsivity in Tourette syndrome: a pilot study.

    Science.gov (United States)

    Tian, Yingfang; Stamova, Boryana; Ander, Bradley P; Jickling, Glen C; Gunther, Joan R; Corbett, Blythe A; Bos-Veneman, Netty G P; Hoekstra, Pieter J; Schweitzer, Julie B; Sharp, Frank R

    2012-10-30

    Inattentiveness, impulsivity and hyperactivity are the primary behaviors associated with attention-deficit hyperactivity disorder (ADHD). Previous studies showed that peripheral blood gene expression signatures can mirror central nervous system disease. Tourette syndrome (TS) is associated with inattention (IA) and hyperactivity/impulsivity (HI) symptoms over 50% of the time. This study determined if gene expression in blood correlated significantly with IA and/or HI rating scale scores in participants with TS. RNA was isolated from the blood of 21 participants with TS, and gene expression measured on Affymetrix human U133 Plus 2.0 arrays. To identify the genes that correlated with Conners' Parents Ratings of IA and HI ratings of symptoms, an analysis of covariance (ANCOVA) was performed, controlling for age, gender and batch. There were 1201 gene probesets that correlated with IA scales, 1625 that correlated with HI scales, and 262 that correlated with both IA and HI scale scores (P0.4). Immune, catecholamine and other neurotransmitter pathways were associated with IA and HI behaviors. A number of the identified genes (n=27) have previously been reported in ADHD genetic studies. Many more genes correlated with either IA or HI scales alone compared to those that correlated with both IA and HI scales. These findings support the concept that the pathophysiology of ADHD and/or its subtypes in TS may involve the interaction of multiple genes. These preliminary data also suggest gene expression may be useful for studying IA and HI symptoms that relate to ADHD in TS and perhaps non-TS participants. These results will need to be confirmed in future studies.

  11. An Investigation of Toxic Shock Syndrome Toxin-1 Gene in Methicillin-Resistant Clinical Strains of Staphylococcus aureus using Multiplex PCR Method

    Directory of Open Access Journals (Sweden)

    mohammad bokaiean

    2017-03-01

    Full Text Available Background and Objectives: Toxins produced by the bacteria are one of the most common cases, which can, together with other bacterial pathogens, cause or aggravate the disease. One of the diseases caused by bacterial toxins, is toxic shock syndrome. The tst gene encodes this toxin that can be easily transferred between different strains of Staphylococcus aureus. In this study, toxic shock syndrome toxin-1 gene was investigated in methicillin-resistant clinical strains of Staphylococcus aureus using multiplex PCR method. Methods: This study is a cross-sectional study, during a 9 month period, 470 samples were collected from patients hospitalized in different wards of treatment centers of Zahedan University of Medical Sciences in 2015. Phenotypic method was used for isolation and initial screening. Oxacillin and Cefoxitin discs were used. After isolation of resistant strains, femA and mecA genes and tst gene were investigated using phenotypic method and multiplex PCR method, respectively. Results: Of 170 clinical isolates of Staphylococcus aureus, 93 isolates were phenotypically methicillin-resistant, among which 89 isolates had mecA gene and 14 isolates had tst gene. Conclusion: The results indicated that the prevalence of methicillin-resistant strains and the strains carrying causative gene for TSST1, is high in Zahedan. Also, circulation of these isolates can lead to much more severe effects in individuals with weak immune system.

  12. Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.

    Science.gov (United States)

    Thompson, Miles D; Comings, David E; Abu-Ghazalah, Rashid; Jereseh, Yousef; Lin, Leo; Wade, Judy; Sakurai, Takeshi; Tokita, Shigeru; Yoshida, Tetsuo; Tanaka, Hirokazu; Yanagisawa, Masashi; Burnham, W McIntyre; Moldofsky, Harvey

    2004-08-15

    The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. Copyright 2004 Wiley-Liss, Inc.

  13. Irritable bowel syndrome and endometriosis: New insights for old diseases.

    Science.gov (United States)

    Viganò, Davide; Zara, Federica; Usai, Paolo

    2018-03-01

    Irritable bowel syndrome and endometriosis are two diseases affecting a significant part of the female population, either together or individually, with remarkable consequences in the quality of life. Several studies suggest an epidemiological association between them. Their association may not be just an epidemiological phenomenon, but the manifestation of a pathophysiological correlation, which probably generates a mutual promotion phenomenon. In particular, both clinical entities share the presence of a chronic low-grade inflammatory state at the basis of the disease persistence. Recognizing this association is highly significant due to their prevalence and the common clinical manifestation occurring with a chronic abdominal pain. A further multi disciplinary approach is suggested in these patients' management in order to achieve an adequate diagnostic work up and a targeted therapy. This paper analyses some common pathophysiological mechanisms, such as activation of mast cell line, neuronal inflammation, dysbiosis and impaired intestinal permeability. The aim was to investigate their presence in both IBS and endometriosis, and to show the complexity of their relationship in the generation and maintenance of chronic inflammation. Copyright © 2017. Published by Elsevier Ltd.

  14. Cushing syndrome: maybe not so uncommon of an endocrine disease.

    Science.gov (United States)

    Guaraldi, Federica; Salvatori, Roberto

    2012-01-01

    Cushing syndrome (CS) is the result of extended exposure to excessive glucocorticoids from endogenous or exogenous sources. Traditionally, the most common cause of endogenous CS is a pituitary adenoma (Cushing disease). Less common causes are adrenocortical tumors and extrapituitary adrenocorticotropin-producing neoplasias. This review provides updated information regarding the potential for increased prevalence of CS in specific patient populations. Here the authors provide to family physicians clinical guidance for recognition of CS by presenting a case, discussing the advantages/disadvantages of the diagnostic tests, and discussing information about the treatment options. CS is expected to have an incidence of 10 to 15 people per million; however, studies of patients with diabetes, obesity, hypertension, and osteoporosis found a high prevalence of CS among these populations. The clinical manifestations of CS range from the distinctive clinical features (purple striae, facial plethora, proximal myopathy) to common conditions such as hypertension, obesity, and diabetes. Clinical practice guidelines recommend biochemical tests to screen patients for CS; however, the sensitivity and specificity of these tests vary, so a careful analysis must be performed to avoid misdiagnosis. CS is challenging to diagnose. Nevertheless, with a systematic approach to testing patients and an increased awareness of the high-risk patient populations, the disease can be identified in a timely manner.

  15. Relapse of nephrotic syndrome triggered by Kawasaki disease.

    Science.gov (United States)

    Maeda, Ryo; Kawasaki, Yukihiko; Suzuki, Shigeo; Ohara, Shinichiro; Kazuhide, Suyama; Hosoya, Mitsuaki

    2018-05-01

    Minor infections, allergies, insect bites, and bee stings are commonly reported causes of nephrotic syndrome (NS). Herein, we report, to the best of our knowledge, the first case of NS relapse due to Kawasaki disease (KD). An 8-year-old boy presented with high fever of 4-day duration. He had developed steroid-dependent NS at the age of 4 years and remained in remission after steroid and mizonbin therapy. Renal biopsy, performed at the age of four, showed minimal change (MC) disease. Upon examination, the patient fulfilled 5 of 6 criteria for KD under the Japanese diagnostic guidelines, with positive proteinuria. He was diagnosed with NS relapse caused by KD. Proteinuria resolved after treatment with intravenous immunoglobulin and cyclosporine A. We present the case of an 8-year-old boy, whose NS relapsed due to KD. To the best of our knowledge, this is the first case report. It is necessary to recognize that KD can trigger relapse of MCNS.

  16. Cuba's Strategy for Alzheimer Disease and Dementia Syndromes.

    Science.gov (United States)

    Bosch-Bayard, Rodolfo I; Llibre-Rodríguez, Juan J; Fernández-Seco, Alberto; Borrego-Calzadilla, Carmen; Carrasco-García, Mayra R; Zayas-Llerena, Tania; Moreno-Carbonell, Carmen R; Reymond-Vasconcelos, Ana G

    2016-10-01

    Dementia is a great challenge to public health in Cuba due to its impact on society and families. Cuba's National Intervention Strategy for Alzheimer Disease and Dementia Syndromes is designed to address this challenge. The Strategy includes working guidelines for primary and secondary care, education about rights of people with cognitive impairment, professional development, research, and health promotion and dementia prevention. An associated action plan, focused on primary care, includes proposals for creation of memory clinics, day centers and comprehensive rehabilitation services for cognitive stimulation. Short-term measures proposed include increasing early detection; creating a dementia morbidity and mortality registry; promoting professional training; providing support for families; and promoting basic and clinical research on dementia. Medium-term proposals aim to reduce dementia incidence and mortality by controlling risk factors and promoting healthy lifestyles, offering new treatment options and optimizing early detection. A set of indicators has been developed to evaluate strategy implementation. With this strategy, Cuba joins the small number of developing countries that have responded to WHO's call to improve care for patients with dementia and alleviate its impact on society and families. KEYWORDS Dementia, Alzheimer disease, aging, national health programs, social stigma, primary prevention, health promotion, civil rights, Cuba.

  17. Growth curves in Down syndrome with congenital heart disease

    Directory of Open Access Journals (Sweden)

    Caroline D’Azevedo Sica

    Full Text Available SUMMARY Introduction: To assess dietary habits, nutritional status and food frequency in children and adolescents with Down syndrome (DS and congenital heart disease (CHD. Additionally, we attempted to compare body mass index (BMI classifications according to the World Health Organization (WHO curves and curves developed for individuals with DS. Method: Cross-sectional study including individuals with DS and CHD treated at a referral center for cardiology, aged 2 to 18 years. Weight, height, BMI, total energy and food frequency were measured. Nutritional status was assessed using BMI for age and gender, using curves for evaluation of patients with DS and those set by the WHO. Results: 68 subjects with DS and CHD were evaluated. Atrioventricular septal defect (AVSD was the most common heart disease (52.9%. There were differences in BMI classification between the curves proposed for patients with DS and those proposed by the WHO. There was an association between consumption of vitamin E and polyunsaturated fatty acids. Conclusion: Results showed that individuals with DS are mostly considered normal weight for age, when evaluated using specific curves for DS. Reviews on specific curves for DS would be the recommended practice for health professionals so as to avoid precipitated diagnosis of overweight and/or obesity in this population.

  18. Aicardi-Goutieres syndrome, a rare neurological disease in children: a new autoimmune disorder?

    Science.gov (United States)

    Fazzi, Elisa; Cattalini, Marco; Orcesi, Simona; Tincani, Angela; Andreoli, L; Balottin, U; De Simone, M; Fredi, M; Facchetti, F; Galli, J; Giliani, S; Izzotti, A; Meini, A; Olivieri, I; Plebani, A

    2013-02-01

    Aicardi-Goutieres syndrome (AGS), described by J. Aicardi and F. Goutieres in 1984, is a rare neurological disease with onset in infancy. It is often misdiagnosed as a sequela of congenital infection or recognized later. Nowadays almost 200 cases are reported all over the world, most of them collected by the International Aicardi-Goutieres Syndrome Association (IAGSA), founded in Pavia (Italy) in 2000. AGS (MIM 225750) is a genetically-determined encephalopathy characterized by severe neurological dysfunction, acquired microcephaly associated with severe prognosis quoad valetudinem, and less frequently also quoad vitam. Some AGS children also develop some symptoms overlapping with systemic lupus erythematosus (SLE). Intracranial calcification, white matter involvement and brain atrophy revealed on MRI, lymphocytosis and elevated levels of interferon alpha (IFN-α) in the cerebrospinal fluid (CSF) are features of both AGS and congenital viral infection. No evidence of congenital infection at serological exams has ever been found. A genetic etiology was hypothesized since the first descriptions, because of the recurrence in families, and demonstrated some years ago. Nowadays five genes (AGS1-5), if mutated, can be responsible for 90% of the cases. The transmission is autosomal recessive but there are also rare "de novo" autosomal dominant cases. Even if pathogenesis is still almost unknown, it seems that responsible genes are involved in nucleic acid reparation mechanisms and consequently in a secondary activation of innate autoimmunity. The relative lack of precise information on pathogenesis and on the evolution of the disease over time has not yet allowed the creation of codified diagnostic and therapeutic models and programs. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype.

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    Shoko Onodera

    Full Text Available Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1 mutations. PTCH1 is a hedgehog (Hh receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported. Recently, mutations in Suppressor of fused homolog (SUFU or PTCH2 were reported in patients with Gorlin syndrome. These facts suggest that multi-layered mutations in Hh pathway may contribute to the development of Gorlin syndrome. We demonstrated multiple mutations of Hh-related genes in addition to PTCH1, which possibly act in an additive or multiplicative manner and lead to Gorlin syndrome. High-throughput sequencing was performed to analyze exome sequences in four unrelated Gorlin syndrome patient genomes. Mutations in PTCH1 gene were detected in all four patients. Specific nucleotide variations or frameshift variations of PTCH1 were identified along with the inferred amino acid changes in all patients. We further filtered 84 different genes which are closely related to Hh signaling. Fifty three of these had enough coverage of over ×30. The sequencing results were filtered and compared to reduce the number of sequence variants identified in each of the affected individuals. We discovered three genes, PTCH2, BOC, and WNT9b, with mutations with a predicted functional impact assessed by MutationTaster2 or PolyPhen-2 (Polymorphism Phenotyping v2 analysis. It is noticeable that PTCH2 and BOC are Hh receptor molecules. No significant mutations were observed in SUFU. Multi-layered mutations in Hh pathway may change the activation level of the Hh signals, which may explain the wide phenotypic variability of Gorlin syndrome.

  20. Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation.

    Science.gov (United States)

    Fakhouri, Fadi; Fila, Marc; Provôt, François; Delmas, Yahsou; Barbet, Christelle; Châtelet, Valérie; Rafat, Cédric; Cailliez, Mathilde; Hogan, Julien; Servais, Aude; Karras, Alexandre; Makdassi, Raifah; Louillet, Feriell; Coindre, Jean-Philippe; Rondeau, Eric; Loirat, Chantal; Frémeaux-Bacchi, Véronique

    2017-01-06

    The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome. Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse. Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients. Copyright © 2016 by the American Society of Nephrology.

  1. Kinesiotherapy of Parkinson`s disease and Parkinson`s syndrom

    OpenAIRE

    Zechovská, Lenka

    2013-01-01

    Author: Lenka Zechovská Institution: Rehabilitation Clinic, Faculty of Medicine in Hradec Králové Title: Kinesiotherapy of Parkinson's disease and Parkinson's syndrome Supervisor: Mgr. Ivana Vondráková Number of pages: 115 Number of attachments: 8 Year of defence: 2013 Keywords: Parkinson's disease, basal ganglia, tremor, rigidity, hypokinesia Bachelor thesis deals with the problems of Parkinson's disease and Parkinson's syndrome. The theoretical part includes the basal ganglia pathophysiolog...

  2. Psychosis and Silent Celiac Disease in a Down Syndrome Adolescent: A Case Report

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    Amparo Morant

    2011-01-01

    Full Text Available Celiac disease is an autoimmune systemic disorder. It presents gastrointestinal and nongastrointestinal manifestations as well as associated conditions. We report a 16-year-old Down syndrome girl who presented psychosis symptomatology, and she was diagnosed as having silent celiac disease. Olanzapine treatment and gluten-free diet were satisfactory. It is necessary to consider celiac disease in Down syndrome patients with psychiatric symptoms, mainly psychotic symptomatology.

  3. Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

    Science.gov (United States)

    Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

    2018-04-01

    Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P1.5-fold change, Pfetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis, angiogenesis

  4. Leveraging model legume information to find candidate genes for soybean sudden death syndrome using the legume information system.

    Science.gov (United States)

    Gonzales, Michael D; Gajendran, Kamal; Farmer, Andrew D; Archuleta, Eric; Beavis, William D

    2007-01-01

    Comparative genomics is an emerging and powerful approach to achieve crop improvement. Using comparative genomics, information from model plant species can accelerate the discovery of genes responsible for disease and pest resistance, tolerance to plant stresses such as drought, and enhanced nutritional value including production of anti-oxidants and anti-cancer compounds. We demonstrate here how to use the Legume Information System for a comparative genomics study, leveraging genomic information from Medicago truncatula (barrel medic), the model legume, to find candidate genes involved with sudden death syndrome (SDS) in Glycine max (soybean). Specifically, genetic maps, physical maps, and annotated tentative consensus and expressed sequence tag (EST) sequences from G. max and M. truncatula can be compared. In addition, the recently published M. truncatula genomic sequences can be used to identify M. truncatula candidate genes in a genomic region syntenic to a quantitative trait loci region for SDS in soybean. Genomic sequences of candidate genes from M. truncatula can then be used to identify ESTs with sequence similarities from soybean for primer design and cloning of potential soybean disease causing alleles.

  5. The Utility of Next-Generation Sequencing in Gene Discovery for Mutation-Negative Patients with Rett Syndrome

    Science.gov (United States)

    Gold, Wendy Anne; Christodoulou, John

    2015-01-01

    Rett syndrome (RTT) is a rare, severe disorder of neuronal plasticity that predominantly affects girls. Girls with RTT usually appear asymptomatic in the first 6–18 months of life, but gradually develop severe motor, cognitive, and behavioral abnormalities that persist for life. A predominance of neuronal and synaptic dysfunction, with altered excitatory–inhibitory neuronal synaptic transmission and synaptic plasticity, are overarching features of RTT in children and in mouse models. Over 90% of patients with classical RTT have mutations in the X-linked methyl-CpG-binding (MECP2) gene, while other genes, including cyclin-dependent kinase-like 5 (CDKL5), Forkhead box protein G1 (FOXG1), myocyte-specific enhancer factor 2C (MEF2C), and transcription factor 4 (TCF4), have been associated with phenotypes overlapping with RTT. However, there remain a proportion of patients who carry a clinical diagnosis of RTT, but who are mutation negative. In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies, making whole-exome and even whole-genome sequencing possible strategies for the detection of rare and de novo mutations, aiding the discovery of novel disease genes. Here, we review the recent progress that is emerging in identifying pathogenic variations, specifically from exome sequencing in RTT patients, and emphasize the need for the use of this technology to identify known and new disease genes in RTT patients. PMID:26236194

  6. Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Laura Ibanez

    2018-04-01

    Full Text Available Background: The prevalence of dementia in Parkinson disease (PD increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established.Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients.Methods: We analyzed the coding regions of the amyloid-beta precursor protein (APP, Presenilin 1 and 2 (PSEN1, PSEN2, and Granulin (GRN genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES data by single variant and gene base (SKAT-O and burden tests analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE or the Montreal Cognitive Assessment (MoCA. The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status.Results: Known AD pathogenic mutations in the PSEN1 (p.A79V and PSEN2 (p.V148I genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2, and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients (p = 2.0 × 10−4, independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site.Conclusions: Pathogenic mutations in

  7. Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.

    Science.gov (United States)

    Lin, Peijie; Nicholls, Laura; Assareh, Hassan; Fang, Zhiming; Amos, Timothy G; Edwards, Richard J; Assareh, Amelia A; Voineagu, Irina

    2016-06-06

    MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.

  8. Delusional Jealousy (Othello Syndrome) in