WorldWideScience

Sample records for autosomal-recessive hypomaturation amelogenesis

  1. Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Tran Le, C G; Yildirim, M; Gencay, K; Lee, Z H; Kim, J-W

    2014-04-01

    Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (SLC24A4) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the SLC24A4 gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3' UTR. This is the first report of exonal deletion in SLC24A4 providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.

  2. Enamelin/ameloblastin gene polymorphisms in autosomal amelogenesis imperfecta among Syrian families.

    Science.gov (United States)

    Dashash, Mayssoon; Bazrafshani, Mohamed Riza; Poulton, Kay; Jaber, Saaed; Naeem, Emad; Blinkhorn, Anthony Stevenson

    2011-02-01

      This study was undertaken to investigate whether a single G deletion within a series of seven G residues (codon 196) at the exon 9-intron 9 boundary of the enamelin gene ENAM and a tri-nucleotide deletion at codon 180 in exon 7 (GGA vs deletion) of ameloblastin gene AMBN could have a role in autosomal amelogenesis imperfecta among affected Syrian families.   A new technique - size-dependent, deletion screening - was developed to detect nucleotide deletion in ENAM and AMBN genes. Twelve Syrian families with autosomal-dominant or -recessive amelogenesis imperfecta were included.   A homozygous/heterozygous mutation in the ENAM gene (152/152, 152/153) was identified in affected members of three families with autosomal-dominant amelogenesis imperfecta and one family with autosomal-recessive amelogenesis imperfecta. A heterozygous mutation (222/225) in the AMBN gene was identified. However, no disease causing mutations was found. The present findings provide useful information for the implication of ENAM gene polymorphism in autosomal-dominant/-recessive amelogenesis imperfecta.   Further investigations are required to identify other genes responsible for the various clinical phenotypes. © 2010 Blackwell Publishing Asia Pty Ltd.

  3. Novel FAM20A mutation causes autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Volodarsky, Michael; Zilberman, Uri; Birk, Ohad S

    2015-06-01

    To relate the peculiar phenotype of amelogenesis imperfecta in a large Bedouin family to the genotype determined by whole genome linkage analysis. Amelogenesis imperfecta (AI) is a broad group of inherited pathologies affecting enamel formation, characterized by variability in phenotypes, causing mutations and modes of inheritance. Autosomal recessive or compound heterozygous mutations in FAM20A, encoding sequence similarity 20, member A, have been shown to cause several AI phenotypes. Five members from a large consanguineous Bedouin family presented with hypoplastic amelogenesis imperfecta with unerupted and resorbed permanent molars. Following Soroka Medical Center IRB approval and informed consent, blood samples were obtained from six affected offspring, five obligatory carriers and two unaffected siblings. Whole genome linkage analysis was performed followed by Sanger sequencing of FAM20A. The sequencing unravelled a novel homozygous deletion mutation in exon 11 (c.1523delC), predicted to insert a premature stop codon (p.Thr508Lysfs*6). We provide an interesting case of novel mutation in this rare disorder, in which the affected kindred is unique in the large number of family members sharing a similar phenotype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Clinical and molecular analysis of the enamelin gene ENAM in Colombian families with autosomal dominant amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Sandra Gutiérrez

    2012-01-01

    Full Text Available In this study, we analyzed the phenotype, clinical characteristics and presence of mutations in the enamelin gene ENAM in five Colombian families with autosomal dominant amelogenesis imperfecta (ADAI. 22 individuals (15 affected and seven unaffected belonging to five Colombian families with ADAI and eight individuals (three affected and five unaffected belonging to three Colombian families with autosomal recessive amelogenesis imperfecta (ARAI that served as controls for molecular alterations and inheritance patterns were studied. Clinical, radiographic and genetic evaluations were done in all individuals. Eight exons and three intron-exon boundaries were sequenced for mutation analysis. Two of the five families with ADAI had the hypoplasic phenotype, two had the hypocalcified phenotype and one had the hypomaturative phenotype. Anterior open bite and mandibular retrognathism were the most frequent skeletal abnormalities in the families with ADAI. No mutations were found. These findings suggest that ADAI in these Colombian families was unrelated to previously described mutations in the ENAM gene. These results also indicate that other regions not included in this investigation, such as the promoter region, introns and other genes should be considered as potential ADAI candidates.

  5. Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta.

    Science.gov (United States)

    Kim, Youn Jung; Kang, Jenny; Seymen, Figen; Koruyucu, Mine; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Lee, Zang Hee; Hu, Jan C-C; Simmer, James P; Kim, Jung-Wook

    2017-01-01

    Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19) and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln) was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180 * and c.389C>T, p.Thr130Ile) were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.

  6. Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Jung-Wook Kim

    2017-04-01

    Full Text Available Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19 and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180* and c.389C>T, p.Thr130Ile were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.

  7. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  8. Pre-Eruptive Coronal Resorption and Congenitally Missing Teeth in a Patient with Amelogenesis Imperfecta: A Case Report

    OpenAIRE

    Miloglu, Ozkan; Karaalioglu, Osman Fatih; Caglayan, Fatma; Yesil, Zeynep Duymus

    2009-01-01

    This clinical report describes a male with autosomal recessive generalized hypoplastic amelogenesis imperfecta. This case is unusual in coronal resorptions prior to tooth eruption. This finding has been reported in some cases of autosomal recessive, autosomal dominant and X linked amelogenesis imperfecta (AI). In reported cases, the defects were usually small and occurred in a maximum of 2 teeth per person. In our case, pre-eruptive coronal resorptions affected three second molar teeth from b...

  9. Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.

    Science.gov (United States)

    Seymen, Figen; Kim, Youn Jung; Lee, Ye Ji; Kang, Jenny; Kim, Tak-Heun; Choi, Hwajung; Koruyucu, Mine; Kasimoglu, Yelda; Tuna, Elif Bahar; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Kim, Young-Jae; Lee, Sang-Hoon; Lee, Zang Hee; Zhang, Hong; Hu, Jan C-C; Simmer, James P; Cho, Eui-Sic; Kim, Jung-Wook

    2016-11-03

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma.

    Science.gov (United States)

    Hegde, Veda; Srikanth, K

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  11. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Veda Hegde

    2014-01-01

    Full Text Available Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  12. A syndrome of epilepsy, dementia, and amelogenesis imperfecta: genetic and clinical features.

    OpenAIRE

    Christodoulou, J; Hall, R K; Menahem, S; Hopkins, I J; Rogers, J G

    1988-01-01

    A family is described with six members affected by a syndrome of epilepsy, dementia, and amelogenesis imperfecta (Kohlschütter's syndrome). An autosomal recessive pattern of inheritance is established for this disorder.

  13. Oral Rehabilitation of a Patient with Amelogenesis Imperfecta

    Science.gov (United States)

    Cogulu, Dilsah; Becerik, Sema; Emingil, Gülnur; Hart, P. Suzanne; Hart, Thomas C.

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder that causes defective enamel development in the primary and permanent teeth. Clinical treatment is important to address the esthetic appearance of affected teeth, reduce dentinal sensitivity, preserve tooth structure, and optimize masticatory function. The purpose of this case report was to describe the diagnosis, treatment planning, and dental rehabilitation of a patient with autosomal recessive amelogenesis imperfecta. The patient was followed for 5 years, and evaluation 3 years after restorations revealed no pathology associated with the rehabilitation. The patient’s esthetic and functional expectations were satisfied. PMID:20108745

  14. An Interdisciplinary Approach for Rehabilitating a Patient with Amelogenesis Imperfecta: A Case Report

    Directory of Open Access Journals (Sweden)

    Niloufar Khodaeian

    2012-01-01

    Full Text Available Amelogenesis imperfecta (AI has been defined as a group of hereditary enamel defects. It can be characterized by enamel hypoplasia, hypomaturation, or hypocalcification of the teeth. AI may be associated with some other dental and skeletal developmental defects. Restoration for patients with this condition should be oriented toward the functional and esthetic rehabilitation. This clinical report describes the oral rehabilitation of a young patient diagnosed with the hypoplastic type of AI in posterior teeth and hypomatured type of AI in anterior teeth.

  15. Association of Amelogenesis Imperfecta and Bartter's Syndrome.

    Science.gov (United States)

    Kumar, A C V; Alekya, V; Krishna, M S V V; Alekya, K; Aruna, M; Reddy, M H K; Sangeetha, B; Ram, R; Kumar, V S

    2017-01-01

    Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

  16. Association of amelogenesis imperfecta and Bartter's syndrome

    Directory of Open Access Journals (Sweden)

    A. C. V. Kumar

    2017-01-01

    Full Text Available Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

  17. A multidisciplinary approach for the diagnosis of hypocalcified amelogenesis imperfecta in two Chilean families.

    Science.gov (United States)

    Urzúa, Blanca; Ortega-Pinto, Ana; Farias, Daniela Adorno; Franco, Eugenia; Morales-Bozo, Irene; Moncada, Gustavo; Escobar-Pezoa, Nicolás; Scholz, Ursula; Cifuentes, Victor

    2012-01-01

    The purpose of this study was to conduct a multidisciplinary analysis of a specific type of tooth enamel disturbance (amelogenesis imperfecta) affecting two Chilean families to obtain a precise diagnosis and to investigate possible underlying mutations. Two non-related families affected with amelogenesis imperfecta were evaluated with clinical, radiographic and histopathological methods. Furthermore, pedigrees of both families were constructed and the presence of eight mutations in the enamelin gene (ENAM) and three mutations in the enamelysin gene (MMP-20) were investigated by PCR and direct sequencing. In the two affected patients, the dental malformation presented as soft and easily disintegrated enamel and exposed dark dentin. Neither of the affected individuals presented with a dental and skeletal open bite. Histologically, a high level of an organic matrix with prismatic organization was found. Genetic analysis indicated that the condition is autosomal recessive in one family and either autosomal recessive or due to a new mutation in the other family. Molecular mutational analysis revealed that none of the eight mutations previously described in the ENAM gene or the three mutations in the MMP-20 gene were present in the probands. A multidisciplinary analysis allowed for a diagnosis of hypocalcified amelogenesis imperfecta, Witkop type III, which was unrelated to previously described mutations in the ENAM or MMP-20 genes.

  18. Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Aldred Michael

    2007-04-01

    Full Text Available Abstract Amelogenesis imperfecta (AI represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations.

  19. Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Muto Taro

    2012-06-01

    Full Text Available Abstract Background Amelogenesis imperfecta (AI is an inherited disorder characterized by abnormal formation of tooth enamel. Although several genes responsible for AI have been reported, not all causative genes for human AI have been identified to date. AMI rat has been reported as an autosomal recessive mutant with hypoplastic AI isolated from a colony of stroke-prone spontaneously hypertensive rat strain, but the causative gene has not yet been clarified. Through a genetic screen, we identified the causative gene of autosomal recessive AI in AMI and analyzed its role in amelogenesis. Methods cDNA sequencing of possible AI-candidate genes so far identified using total RNA of day 6 AMI rat molars identified a novel responsible mutation in specificity protein 6 (Sp6. Genetic linkage analysis was performed between Sp6 and AI phenotype in AMI. To understand a role of SP6 in AI, we generated the transgenic rats harboring Sp6 transgene in AMI (Ami/Ami + Tg. Histological analyses were performed using the thin sections of control rats, AMI, and Ami/Ami + Tg incisors in maxillae, respectively. Results We found the novel genetic linkage between a 2-bp insertional mutation of Sp6 gene and the AI phenotype in AMI rats. The position of mutation was located in the coding region of Sp6, which caused frameshift mutation and disruption of the third zinc finger domain of SP6 with 11 cryptic amino acid residues and a stop codon. Transfection studies showed that the mutant protein can be translated and localized in the nucleus in the same manner as the wild-type SP6 protein. When we introduced the CMV promoter-driven wild-type Sp6 transgene into AMI rats, the SP6 protein was ectopically expressed in the maturation stage of ameloblasts associated with the extended maturation stage and the shortened reduced stage without any other phenotypical changes. Conclusion We propose the addition of Sp6 mutation as a new molecular diagnostic criterion for the

  20. Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta

    Science.gov (United States)

    2012-01-01

    Background Amelogenesis imperfecta (AI) is an inherited disorder characterized by abnormal formation of tooth enamel. Although several genes responsible for AI have been reported, not all causative genes for human AI have been identified to date. AMI rat has been reported as an autosomal recessive mutant with hypoplastic AI isolated from a colony of stroke-prone spontaneously hypertensive rat strain, but the causative gene has not yet been clarified. Through a genetic screen, we identified the causative gene of autosomal recessive AI in AMI and analyzed its role in amelogenesis. Methods cDNA sequencing of possible AI-candidate genes so far identified using total RNA of day 6 AMI rat molars identified a novel responsible mutation in specificity protein 6 (Sp6). Genetic linkage analysis was performed between Sp6 and AI phenotype in AMI. To understand a role of SP6 in AI, we generated the transgenic rats harboring Sp6 transgene in AMI (Ami/Ami + Tg). Histological analyses were performed using the thin sections of control rats, AMI, and Ami/Ami + Tg incisors in maxillae, respectively. Results We found the novel genetic linkage between a 2-bp insertional mutation of Sp6 gene and the AI phenotype in AMI rats. The position of mutation was located in the coding region of Sp6, which caused frameshift mutation and disruption of the third zinc finger domain of SP6 with 11 cryptic amino acid residues and a stop codon. Transfection studies showed that the mutant protein can be translated and localized in the nucleus in the same manner as the wild-type SP6 protein. When we introduced the CMV promoter-driven wild-type Sp6 transgene into AMI rats, the SP6 protein was ectopically expressed in the maturation stage of ameloblasts associated with the extended maturation stage and the shortened reduced stage without any other phenotypical changes. Conclusion We propose the addition of Sp6 mutation as a new molecular diagnostic criterion for the autosomal recessive AI patients

  1. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S; Reid, Bryan M; Lin, Brent P; Wang, Susan J; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2014-04-15

    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell-ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell-matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects.

  2. Autosomal recessive anhidrotic ectodermal dysplasia: A rare entity

    Directory of Open Access Journals (Sweden)

    Sangita Ghosh

    2014-01-01

    Full Text Available We describe a case of anhidrotic ectodermal dysplasia (AED with an autosomal recessive mode of inheritance, a very rare entity, in a 2-year-old female child of two asymptomatic, consanguineous parents. Their previous child also had a similar condition. Autosomal recessive AED (AR-AED can have its full expression both in males and females and it is clinically indistinguishable from the x-linked recessive AED (XL-AED, which is the most common type of ectodermal dysplasia. Unlike the partially symptomatic carriers of XL-AED, the heterozygotes of AR-AED are phenotypically asymptomatic.

  3. Missense Mutation in Fam83H Gene in Iranian Patients with Amelogenesis Imperfecta.

    Science.gov (United States)

    Pourhashemi, S Jalal; Ghandehari Motlagh, Mehdi; Meighani, Ghasem; Ebrahimi Takaloo, Azadeh; Mansouri, Mahsa; Mohandes, Fatemeh; Mirzaii, Maryam; Khoshzaban, Ahad; Moshtaghi, Faranak; Abedkhojasteh, Hoda; Heidari, Mansour

    2014-12-01

    Amelogenesis Imperfecta (AI) is a disorder of tooth development where there is an abnormal formation of enamel or the external layer of teeth. The aim of this study was to screen mutations in the four most important candidate genes, ENAM, KLK4, MMP20 and FAM83H responsible for amelogenesis imperfect. Geneomic DNA was isolated from five Iranian families with 22 members affected with enamel malformations. The PCR amplifications were typically carried out for amplification the coding regions for AI patients and unaffected family members. The PCR products were subjected to direct sequencing. The pedigree analysis was performed using Cyrillic software. One family had four affected members with autosomal dominant hypocalcified amelogenesis imperfecta (ADHPCAI); pedigree analysis revealed four consanguineous families with 18 patients with autosomal recessive hypoplastic amelogenesis imperfecta (ARHPAI). One non-synonymous single-nucleotide substitution, c.1150T>A, p. Ser 342Thr was identified in the FAM83H, which resulted in ADHCAI. Furthermore, different polymorphisms or unclassified variants were detected in MMP20, ENAM and KLK4. Our results are consistent with other studies and provide further evidence for pathogenic mutations of FAM83H gene. These findings suggest different loci and genes could be implicated in the pathogenesis of AI.

  4. Novel ITGB6 mutation in autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Koruyucu, M; Gencay, K; Bayram, M; Tuna, E B; Lee, Z H; Kim, J-W

    2015-05-01

    Hereditary defects in tooth enamel formation, amelogenesis imperfecta (AI), can be non-syndromic or syndromic phenotype. Integrins are signaling proteins that mediate cell-cell and cell-extracellular matrix communication, and their involvement in tooth development is well known. The purposes of this study were to identify genetic cause of an AI family and molecular pathogenesis underlying defective enamel formation. We recruited a Turkish family with isolated AI and performed mutational analyses to clarify the underlying molecular genetic etiology. Autozygosity mapping and exome sequencing identified a novel homozygous ITGB6 transversion mutation in exon 4 (c.517G>C, p.Gly173Arg). The glycine at this position in the middle of the βI-domain is conserved among a wide range of vertebrate orthologs and human paralogs. Clinically, the enamel was generally thin and pitted with pigmentation. Thicker enamel was noted at the cervical area of the molars. In this study, we identified a novel homozygous ITGB6 mutation causing isolated AI, and this advances the understanding of normal and pathologic enamel development. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Andhidrotic ectodermal dysplasia-autosomal recessive form

    Directory of Open Access Journals (Sweden)

    Inamadar Arun

    1994-01-01

    Full Text Available Anhidrotic ectodermal dysplasia with classical features in 2 sisters is reported. The mode of inheritance in these seems to be autosomal recessive; which is a very rare occurrence.

  6. Mutations in C4orf26, Encoding a Peptide with In Vitro Hydroxyapatite Crystal Nucleation and Growth Activity, Cause Amelogenesis Imperfecta

    Science.gov (United States)

    Parry, David A.; Brookes, Steven J.; Logan, Clare V.; Poulter, James A.; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C.; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E.; Carr, Ian M.; Taylor, Graham R.; Johnson, Colin A.; Aldred, Michael J.; Dixon, Michael J.; Wright, J. Tim; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2012-01-01

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein’s phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis. PMID:22901946

  7. A rare association--amelogenesis imperfecta, platispondyly and bicytopenia: a case report.

    Science.gov (United States)

    Laouina, Samir; El Alaoui, Siham Chafai; Amezian, Rachida; Al Bouzidi, Abderrahmane; Sefiani, Abdelaziz; El Alloussi, Mustapha

    2015-10-28

    Amelogenesis imperfecta is an inherited disease characterized by generalized structural abnormalities of the enamel on all teeth, including both primary and permanent dentition. To the best of our knowledge, this is the first case report of a rare association of amelogenesis imperfecta, platyspondyly, and bicytopenia. A 5-year-old Moroccan boy was examined in the Centre for Dental Consultation and Treatment, Faculty of Dentistry, Rabat. He was a child of consanguineous parents (first degree). The child failed to thrive (-4 standard deviation score) and displayed delayed overall development. A dental examination revealed a hypoplastic amelogenesis imperfecta with a bacterial biofilm deposit on tooth surfaces. A complete blood count revealed bicytopenia (normocytic-normochromic anemia with thrombocytopenia). A radiographic examination of the spinal column showed a deviation of the spine in the frontal plane in the form of thoracolumbar scoliosis. The interpedicular distance was not expanded; but a mild platyspondyly exists, especially pronounced in T11 and T12. No other family members presented amelogenesis imperfecta, bicytopenia, or platyspondyly. The consanguineous marriage suggested an autosomal recessive mode of inheritance. Further studies are necessary to clarify the genetic defect producing this syndrome, and the symptomatic associations of amelogenesis imperfecta, platyspondyly and bicytopenia.

  8. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis

    OpenAIRE

    Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P.; Rogaeva, Ekaterina A.; St George-Hyslop, Peter H.; Bernardi, Giorgio; Kawarai, Toshitaka

    2010-01-01

    The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite ...

  9. Aesthetic composite veneers for an adult patient with amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Brignall, Ian; Mehta, Shamir B; Banerji, Subir; Millar, Brian J

    2011-11-01

    This case has been presented as part of the continual assessment requirement for the MSc in Aesthetic Dentistry, King's College Dental Institute. Amelogenesis imperfecta (AI) is a hereditary disorder of enamel formation, affecting both the permanent and deciduous dentitions. It can be classified into hypoplastic, hypomaturation and hypocalcified types and presents with different hereditary patterns. The aim of this article is to provide an overview of amelogenesis imperfecta, including a detailed case report for an aesthetically concerned adult patient presenting in general practice with a Witkop's Type IA defect managed with the placement of direct, layered resin composite veneers. Amelogenesis imperfecta patients are susceptible to the restorative cycle of replacement restorations like any other patient, but start with a distinct disadvantage.This case report demonstrates a minimally invasive, relatively simple and cost-effective option for the aesthetic correction of a case of hypoplastic amelogenesis imperfecta with layered composite veneers. Dent Update 2011; 38:594-603

  10. Noninvasive esthetic treatment for hypomaturation amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Nahsan, Flávia Pardo Salata; Silva, Luciana Mendonça da; Lima, Thiago Mendes de; Bertocco, Verônica Pereira de Lima; Chui, Fabíola Mendonça da Silva; Martins, Leandro de Moura

    2016-01-01

    Enamel alterations, such as amelogenesis imperfecta, can compromise the harmony of the smile and the patient's self-esteem and may cause tooth sensitivity. A simple and effective treatment approach uses the natural stratification of composite resins to mask deficient enamel formation and mimic the natural appearance of the substrate. The operative steps and principles for restorative success are described in this case report with 36-month follow-up.

  11. Autosomal Recessive Polycystic Kidney Disease: Antenatal Diagnosis and Histopathological Correlation

    Directory of Open Access Journals (Sweden)

    Dayananda Kumar Rajanna

    2013-01-01

    Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is one of the most common inheritable disease manifesting in infancy and childhood with a frequency of 1:6,000 to 1:55,000 births. The patient in her second trimester presented with a history of amenorrhea. Ultrasound examination revealed bilateral, enlarged, hyperechogenic kidneys, placentomegaly, and severe oligohydramnios. The pregnancy was terminated. An autopsy was performed on the fetus. Both the kidneys were found to be enlarged and the cut surface showed numerous cysts. The liver sections showed changes due to fibrosis. The final diagnosis of autosomal recessive polycystic kidney disease was made based on these findings. In this article, we correlate the ante-natal ultrasound and histopathological findings in autosomal recessive polycystic kidney disease.

  12. Unilateral Autosomal Recessive Anophthalmia in a Patient with Cystic Craniopharyngioma

    Science.gov (United States)

    Kumar, Amandeep; Bansal, Ankit; Garg, Ajay; Sharma, Bhawani S.

    2014-01-01

    Abstract Anophthalmia is a rare ocular malformation. It is a genetically determined disorder and is typically associated with syndromes. However, sporadic nonsyndromic familial as well as non-familial cases of anophthalmia have also been reported. Non-syndromic familial cases are usually bilateral and have been attributed to autosomal recessive, autosomal dominant, and X-linked inheritance patterns. The authors hereby report a rare case of autosomal recessive unilateral anophthalmia in a patient with no other associated congenital anomaly. Patient was operated for craniopharyngioma. The clinical, radiological and intraoperative findings are discussed. PMID:27928292

  13. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.

    Science.gov (United States)

    Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P; Rogaeva, Ekaterina A; St George-Hyslop, Peter H; Bernardi, Giorgio; Kawarai, Toshitaka

    2010-02-01

    The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.

  14. Autosomal recessive mode of inheritance of a Coffin-Siris like syndrome.

    Science.gov (United States)

    Bonioli, E; Palmieri, A; Bertola, A; Bellini, C

    1995-01-01

    Autosomal recessive mode of inheritance of a Coffin-Siris like syndrome: Coffin-Siris syndrome is a rare mental retardation/multiple congenital anomalies syndrome; so far its pattern of inheritance is under debate. We report a child affected by this syndrome, the pedigree of which is consistent with autosomal recessive inheritance.

  15. Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.

    Science.gov (United States)

    Parry, David A; Brookes, Steven J; Logan, Clare V; Poulter, James A; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E; Carr, Ian M; Taylor, Graham R; Johnson, Colin A; Aldred, Michael J; Dixon, Michael J; Wright, J Tim; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2012-09-07

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Autosomal recessive Charcot-Marie-Tooth neuropathy.

    Science.gov (United States)

    Espinós, Carmen; Calpena, Eduardo; Martínez-Rubio, Dolores; Lupo, Vincenzo

    2012-01-01

    Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy that comprises a complex group of more than 50 diseases, is the most common inherited neuropathy. CMT is generally divided into demyelinating forms, axonal forms and intermediate forms. CMT is also characterized by a wide genetic heterogeneity with 29 genes and more than 30 loci involved. The most common pattern of inheritance is autosomal dominant (AD), although autosomal recessive (AR) forms are more frequent in Mediterranean countries. In this chapter we give an overview of the associated genes, mechanisms and epidemiology of AR-CMT forms and their associated phenotypes.

  17. Further evidence for causal FAM20A mutations and first case of amelogenesis imperfecta and gingival hyperplasia syndrome in Morocco: a case report.

    Science.gov (United States)

    Cherkaoui Jaouad, Imane; El Alloussi, Mustapha; Chafai El Alaoui, Siham; Laarabi, Fatima Zahra; Lyahyai, Jaber; Sefiani, Abdelaziz

    2015-01-30

    Amelogenesis imperfecta represents a group of developmental conditions, clinically and genetically heterogeneous, that affect the structure and clinical appearance of enamel. Amelogenesis imperfecta occurred as an isolated trait or as part of a genetic syndrome. Recently, disease-causing mutations in the FAM20A gene were identified, in families with an autosomal recessive syndrome associating amelogenesis imperfecta and gingival fibromatosis. We report, the first description of a Moroccan patient with amelogenesis imperfecta and gingival fibromatosis, in whom we performed Sanger sequencing of the entire coding sequence of FAM20A and identified a homozygous mutation in the FAM20A gene (c.34_35delCT), already reported in a family with this syndrome. Our finding confirms that the mutations of FAM20A gene are causative for amelogenesis imperfecta and gingival fibromatosis and underlines the recurrent character of the c.34_35delCT in two different ethnic groups.

  18. Arrestin gene mutations in autosomal recessive retinitis pigmentosa.

    Science.gov (United States)

    Nakazawa, M; Wada, Y; Tamai, M

    1998-04-01

    To assess the clinical and molecular genetic studies of patients with autosomal recessive retinitis pigmentosa associated with a mutation in the arrestin gene. Results of molecular genetic screening and case reports with DNA analysis and clinical features. University medical center. One hundred twenty anamnestically unrelated patients with autosomal recessive retinitis pigmentosa. DNA analysis was performed by single strand conformation polymorphism followed by nucleotide sequencing to search for a mutation in exon 11 of the arrestin gene. Clinical features were characterized by visual acuity slitlamp biomicroscopy, fundus examinations, fluorescein angiography, kinetic visual field testing, and electroretinography. We identified 3 unrelated patients with retinitis pigmentosa associated with a homozygous 1-base-pair deletion mutation in codon 309 of the arrestin gene designated as 1147delA. All 3 patients showed pigmentary retinal degeneration in the midperipheral area with or without macular involvement. Patient 1 had a sibling with Oguchi disease associated with the same mutation. Patient 2 demonstrated pigmentary retinal degeneration associated with a golden-yellow reflex in the peripheral fundus. Patients 1 and 3 showed features of retinitis pigmentosa without the golden-yellow fundus reflex. Although the arrestin 1147delA has been known as a frequent cause of Oguchi disease, this mutation also may be related to the pathogenesis of autosomal recessive retinitis pigmentosa. This phenomenon may provide evidence of variable expressivity of the mutation in the arrestin gene.

  19. Oral rehabilitation of a patient with amelogenesis imperfecta using removable overlay denture: a clinical report.

    Science.gov (United States)

    Ghodsi, S; Rasaeipour, S; Vojdani, M

    2012-03-01

    The aim of this study was oral rehabilitation of 17-year old patient with amelogenesis imperfecta using removable overlay denture in order to satisfy her esthetic and functional expectations and enhance her self-image. Amelogenesis imperfecta (AI) is a group of genetic disorders that primarily affect the quality and quantity of amelogenesis in both primary and permanent dentitions. The main clinical characteristics are severe attrition, tooth sensitivity and unesthetic appearance. This clinical report illustrates the oral rehabilitation of a 17-year-old girl with hypoplastic-hypomature type of AI with cobalt-chromium (Co-Cr) overlay removable partial denture (ORPD) that is one of the most economical and biocompatible replacements for noble metal and nickel-chromium (Ni-Cr) alloy. The presented case report suggests that Co-Cr ORPD can be a good temporary or even permanent treatment option for AI patients with limited budget, low esthetic concerns or medical limitations. There are major advantages in cast metal ORPDs; they are simpler, less traumatic and less expensive than fixed prosthetic options. This case report supports their use in patients with amelogenesis imperfecta.

  20. Evidence for nonallelic genetic heterogeneity in autosomal recessive retinitis pigmentosa

    NARCIS (Netherlands)

    Bleeker-Wagemakers, L. M.; Gal, A.; Kumar-Singh, R.; van den Born, L. I.; Li, Y.; Schwinger, E.; Sandkuijl, L. A.; Bergen, A. A.; Kenna, P.; Humphries, P.

    1992-01-01

    Recent evidence suggesting the involvement of mutant rhodopsin proteins in the pathogenesis of autosomal recessive retinitis pigmentosa has prompted us to investigate whether this form of the disease shows non-allelic genetic heterogeneity, as has previously been shown to be the case in autosomal

  1. Autosomal recessive type II hereditary motor and sensory neuropathy with acrodystrophy.

    Science.gov (United States)

    Thomas, P K; Claus, D; King, R H

    1999-02-01

    A family is described with presumed autosomal recessive inheritance in which three siblings developed a progressive neuropathy that combined limb weakness and severe distal sensory loss leading to prominent mutilating changes. Electrophysiological and nerve biopsy findings indicated an axonopathy. The disorder is therefore classifiable as type II hereditary motor and sensory neuropathy (HMSN II). The clinical features differ from those reported in previously described cases of autosomal recessive HMSN II. This disorder may therefore represent a new variant.

  2. Amelogenesis Imperfecta - An account of Three Generations affected in a Family

    Directory of Open Access Journals (Sweden)

    G Sarat

    2004-01-01

    Full Text Available Amelogenesis Imperfecta is a hereditary condition affecting dental enamel without any systemic manifestation. This condition can be inherited as either Autosomal or X-linked. In this case report, we discuss with the help of Pedigree Analysis, an account of three generations in a family affected by Autosomal Dominant, Hypoplastic type of Amelogenesis Imperfecta.

  3. Amelogenesis Imperfecta: A Non-Invasive Approach to Improve Esthetics in Young Patients. Report of Two Cases.

    Science.gov (United States)

    Cagetti, Maria Grazia; Cattaneo, Stefano; Hu, Ye Qing; Campus, Guglielmo

    Objective-Evaluate esthetic and functional efficacy of infiltrant resin (Icon, DMG, Hamburg, Germany) in Amelogenesis Imperfecta's treatment. Two adolescent patients, G.S. (13 years old) and C.M. (15 years old), affected by the hypomaturation type of Amelogenesis Imperfecta, were treated with Icon resin and were followed for twelve months. Treated teeth show an excellent aesthetical result immediately after the resin application, effect that lasts in the long-term (six and twelve months follow-up examinations); the dental wear's progression seems to be clinically arrested. Resin infiltration has proven to be a minimal invasive treatment for dental discoloration, less aggressive than conventional procedures. This approach might be recommended for a stable esthetical improvement in moderate AI's lesions especially in children and adolescents.

  4. Autosomal recessive osteopetrosis with a unique imaging finding: multiple encephaloceles

    Energy Technology Data Exchange (ETDEWEB)

    Saglam, Dilek; Bilgici, Meltem Ceyhan; Bekci, Tuemay [Ondokuz Mayis University, Department of Radiology, School of Medicine, Kurupelit, Samsun (Turkey); Albayrak, Canan; Albayrak, Davut [Ondokuz Mayis University, Department of Pediatrics, School of Medicine, Kurupelit, Samsun (Turkey)

    2017-05-15

    Osteopetrosis is a hereditary form of sclerosing bone dysplasia with various radiological and clinical presentations. The autosomal recessive type, also known as malignant osteopetrosis, is the most severe type, with the early onset of manifestations. A 5-month-old infant was admitted to our hospital with recurrent respiratory tract infections. Chest X-ray and skeletal survey revealed the classic findings of osteopetrosis, including diffuse osteosclerosis and bone within a bone appearance. At follow-up, the patient presented with, thickened calvarium, multiple prominent encephaloceles, and dural calcifications leading to the intracranial clinical manifestations with bilateral hearing and sight loss. Autosomal recessive osteopetrosis is one of the causes of encephaloceles and this finding may become dramatic if untreated. (orig.)

  5. Autosomal recessive osteopetrosis with a unique imaging finding: multiple encephaloceles

    International Nuclear Information System (INIS)

    Saglam, Dilek; Bilgici, Meltem Ceyhan; Bekci, Tuemay; Albayrak, Canan; Albayrak, Davut

    2017-01-01

    Osteopetrosis is a hereditary form of sclerosing bone dysplasia with various radiological and clinical presentations. The autosomal recessive type, also known as malignant osteopetrosis, is the most severe type, with the early onset of manifestations. A 5-month-old infant was admitted to our hospital with recurrent respiratory tract infections. Chest X-ray and skeletal survey revealed the classic findings of osteopetrosis, including diffuse osteosclerosis and bone within a bone appearance. At follow-up, the patient presented with, thickened calvarium, multiple prominent encephaloceles, and dural calcifications leading to the intracranial clinical manifestations with bilateral hearing and sight loss. Autosomal recessive osteopetrosis is one of the causes of encephaloceles and this finding may become dramatic if untreated. (orig.)

  6. Genetics Home Reference: autosomal recessive congenital stationary night blindness

    Science.gov (United States)

    ... collapse boxes. Description Autosomal recessive congenital stationary night blindness is a disorder of the retina , which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing ...

  7. Exome Sequencing and Directed Clinical Phenotyping Diagnose Cholesterol Ester Storage Disease Presenting as Autosomal Recessive Hypercholesterolemia

    NARCIS (Netherlands)

    Stitziel, Nathan O.; Fouchier, Sigrid W.; Sjouke, Barbara; Peloso, Gina M.; Moscoso, Alessa M.; Auer, Paul L.; Goel, Anuj; Gigante, Bruna; Barnes, Timothy A.; Melander, Olle; Orho-Melander, Marju; Duga, Stefano; Sivapalaratnam, Suthesh; Nikpay, Majid; Martinelli, Nicola; Girelli, Domenico; Jackson, Rebecca D.; Kooperberg, Charles; Lange, Leslie A.; Ardissino, Diego; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Reilly, Muredach P.; Rader, Daniel J.; de Faire, Ulf; Schunkert, Heribert; Erdmann, Jeanette; Samani, Nilesh J.; Charnas, Lawrence; Altshuler, David; Gabriel, Stacey; Kastelein, John J. P.; Defesche, Joep C.; Nederveen, Aart J.; Kathiresan, Sekar; Hovingh, G. Kees

    2013-01-01

    Objective Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not

  8. ALS5/SPG11/ KIAA1840 mutations cause autosomal recessive axonal Charcot–Marie–Tooth disease

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L.; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H.; Barsottini, Orlando G. P.; Kawarai, Toshitaka

    2016-01-01

    Abstract Charcot–Marie–Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/ KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot–Marie–Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot–Marie–Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/ KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot–Marie–Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot–Marie–Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot–Marie-Tooth disease (CMT2A2/HMSN2A2/ MFN2 , CMT2B1/ LMNA , CMT2B2/ MED25 , CMT2B5/ NEFL , ARCMT2F/dHMN2B/ HSPB1 , CMT2K/ GDAP1 , CMT2P/ LRSAM1 , CMT2R/ TRIM2 , CMT2S/ IGHMBP2 , CMT2T/ HSJ1 , CMTRID/ COX6A1 , ARAN-NM/ HINT and GAN/ GAN ), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/ PGN , SPG15/ ZFYVE26, SPG21/ ACP33 , SPG35/ FA2H , SPG46/ GBA2 , SPG55/ C12orf65 and SPG56/ CYP2U1 ), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum ( SLC12A6 ) . Mitochondrial disorders related to Charcot–Marie–Tooth disease type 2 were also excluded by sequencing POLG and

  9. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  10. Autosomal recessive retinitis pigmentosa with RP1 mutations is associated with myopia

    NARCIS (Netherlands)

    Chassine, T.; Bocquet, B.; Daien, V.; Avila-Fernandez, A.; Ayuso, C.; Collin, R.W.J.; Corton, M.; Hejtmancik, J.F.; Born, L.I. van den; Klevering, B.J.; Riazuddin, S.A.; Sendon, N.; Lacroux, A.; Meunier, I.; Hamel, C.P.

    2015-01-01

    OBJECTIVE: To determine the refractive error in patients with autosomal recessive retinitis pigmentosa (arRP) caused by RP1 mutations and to compare it with that of other genetic subtypes of RP. METHODS: Twenty-six individuals had arRP with RP1 mutations, 25 had autosomal dominant RP (adRP) with RP1

  11. Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis.

    Science.gov (United States)

    Ferlazzo, Edoardo; Striano, Pasquale; Italiano, Domenico; Calarese, Tiziana; Gasparini, Sara; Vanni, Nicola; Fruscione, Floriana; Genton, Pierre; Zara, Federico

    2016-09-01

    Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis is an extremely rare condition, so far reported in a single family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. Genetic study allowed to identify a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. The mutation decreased C18-ceramide levels. In addition, downregulation of CerS1 in neuroblastoma cell line showed activation of ER stress response and induction of proapoptotic pathways. This observation demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans.

  12. Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

    NARCIS (Netherlands)

    Klevering, B.J.; Blankenagel, A.; Maugeri, A.; Cremers, F.P.M.; Hoyng, C.B.; Rohrschneider, K.

    2002-01-01

    PURPOSE: To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. METHODS: The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were

  13. Disease: H00618 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00618 Amelogenesis imperfecta hypoplastic-hypomaturation with taurodontism (AIHHT) Amelogenesis...t trait. Mouth and dental disease DLX3 [HSA:1747] [KO:K09315] ... Amelogenesis imperfecta and trichodentoos

  14. Autosomal recessive hypophosphataemic rickets with hypercalciuria is not caused by mutations in the type II renal sodium/phosphate cotransporter gene.

    NARCIS (Netherlands)

    Heuvel, L.P.W.J. van den; Koul, K. Op de; Knots, E.; Knoers, N.V.A.M.; Monnens, L.A.H.

    2001-01-01

    BACKGROUND: At present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (HHRH) is unknown. Type II sodium/phosphate cotransporter (NPT2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and

  15. NDST1 missense mutations in autosomal recessive intellectual disability.

    Science.gov (United States)

    Reuter, Miriam S; Musante, Luciana; Hu, Hao; Diederich, Stefan; Sticht, Heinrich; Ekici, Arif B; Uebe, Steffen; Wienker, Thomas F; Bartsch, Oliver; Zechner, Ulrich; Oppitz, Cornelia; Keleman, Krystyna; Jamra, Rami Abou; Najmabadi, Hossein; Schweiger, Susann; Reis, André; Kahrizi, Kimia

    2014-11-01

    NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N-deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in the clinical features, including both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency. Furthermore, in Drosophila, knockdown of sulfateless, the NDST ortholog, impairs long-term memory, highlighting its function in cognition. Our data confirm NDST1 mutations as a cause of autosomal recessive intellectual disability with a distinctive phenotype, and support an important function of NDST1 in human development. © 2014 Wiley Periodicals, Inc.

  16. Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Landau, D.; Shalev, H.; Carmi, Rivka; Ohaly, M. [Univ. of the Negev, Ashkelon (Israel)

    1995-12-04

    The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS. 35 refs., 2 figs., 2 tabs.

  17. Deciphering defective amelogenesis using in vitro culture systems.

    Science.gov (United States)

    Arinawati, Dian Yosi; Miyoshi, Keiko; Tanimura, Ayako; Horiguchi, Taigo; Hagita, Hiroko; Noma, Takafumi

    2018-04-01

    The conventional two-dimensional (2D) in vitro culture system is frequently used to analyze the gene expression with or without extracellular signals. However, the cells derived from primary culture and cell lines frequently deviate the gene expression profile compared to the corresponding in vivo samples, which sometimes misleads the actual gene regulation in vivo. To overcome this gap, we developed the comparative 2D and 3D in vitro culture systems and applied them to the genetic study of amelogenesis imperfecta (AI) as a model. Recently, we found specificity protein 6 (Sp6) mutation in an autosomal-recessive AI rat that was previously named AMI. We constructed 3D structure of ARE-B30 cells (AMI-derived rat dental epithelial cells) or G5 (control wild type cells) combined with RPC-C2A cells (rat pulp cell line) separated by the collagen membrane, while in 2D structure, ARE-B30 or G5 was cultured with or without the collagen membrane. Comparative analysis of amelogenesis-related gene expression in ARE-B30 and G5 using our 2D and 3D in vitro systems revealed distinct expression profiles, showing the causative outcomes. Bone morphogenetic protein 2 and follistatin were reciprocally expressed in G5, but not in ARE-B30 cells. All-or-none expression of amelotin, kallikrein-related peptidase 4, and nerve growth factor receptor was observed in both cell types. In conclusion, our in vitro culture systems detected the phenotypical differences in the expression of the stage-specific amelogenesis-related genes. Parallel analysis with 2D and 3D culture systems may provide a platform to understand the molecular basis for defective amelogenesis caused by Sp6 mutation. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. A Dutch family with autosomal recessively inherited lower motor neuron predominant motor neuron disease due to optineurin mutations

    NARCIS (Netherlands)

    Beeldman, Emma; van der Kooi, Anneke J.; de Visser, Marianne; van Maarle, Merel C.; van Ruissen, Fred; Baas, Frank

    2015-01-01

    Approximately 10% of motor neuron disease (MND) patients report a familial predisposition for MND. Autosomal recessively inherited MND is less common and is most often caused by mutations in the superoxide dismutase 1 (SOD1) gene. In 2010, autosomal recessively inherited mutations in the optineurin

  19. Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia.

    Science.gov (United States)

    Hamza, Wahiba; Ali Pacha, Lamia; Hamadouche, Tarik; Muller, Jean; Drouot, Nathalie; Ferrat, Farida; Makri, Samira; Chaouch, Malika; Tazir, Meriem; Koenig, Michel; Benhassine, Traki

    2015-06-12

    Autosomal recessive cerebellar ataxias (ARCA) are a complex group of neurodegenerative disorders with great genetic and phenotypic heterogeneity, over 30 genes/loci have been associated with more than 20 different clinical forms of ARCA. Genetic heterogeneity combined with highly variable clinical expression of the cerebellar symptoms and overlapping features complicate furthermore the etiological diagnosis of ARCA. The determination of the most frequent mutations and corresponding ataxias, as well as particular features specific to a population, are mandatory to facilitate and speed up the diagnosis process, especially when an appropriate treatment is available. We explored 166 patients (115 families) refered to the neurology units of Algiers central hospitals (Algeria) with a cerebellar ataxia phenotype segregating as an autosomal recessive pattern of inheritance. Genomic DNA was extracted from peripheral blood samples and mutational screening was performed by PCR and direct sequencing or by targeted genomic capture and massive parallel sequencing of 57 genes associated with inherited cerebellar ataxia phenotypes. In this work we report the clinical and molecular results obtained on a large cohort of Algerian patients (110 patients/76 families) with genetically determined autosomal recessive ataxia, representing 9 different types of ARCA and 23 different mutations, including 6 novel ones. The five most common ARCA in this cohort were Friedreich ataxia, ataxia with isolated vitamin E deficiency, ataxia with oculomotor apraxia type 2, autosomal recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1. We report here a large cohort of patients with genetically determined autosomal recessive ataxia and the first study of the genetic context of ARCA in Algeria. This study showed that in Algerian patients, the two most common types of ataxia (Friedreich ataxia and ataxia with isolated vitamin E deficiency) coexist with forms that may be

  20. Two novel mutations in ILDR1 gene cause autosomal recessive ...

    Indian Academy of Sciences (India)

    In a recent screening programme on hearing loss (HL), we examined 17 common autosomal recessive nonsyndromic hearing loss (ARNSHL) genes in every consanguineous Ira- nian family with ARNSHL that was referred to our centre. We first screened GJB2 mutations and then utilized a panel of three to four short ...

  1. Progeria (Hutchison - Gilford syndrome in siblings: In an autosomal recessive pattern of inheritance

    Directory of Open Access Journals (Sweden)

    Raghu Tanjore

    2001-09-01

    Full Text Available Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclcrodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.

  2. Genetic Causes of Putative Autosomal Recessive Intellectual Disability Cases in Hamedan Province

    Directory of Open Access Journals (Sweden)

    Milad Bastami

    2012-04-01

    Full Text Available Objective: The aim of this study was to investigate the genetic causes of autosomal recessive intellectual disabilities (AR-ID in Hamadan province of Iran. Materials & Methods: In this descriptive-analytical cross-sectional study, 25 families with more than one affected with putative autosomal recessive intellectual disability were chosen with collaboration of Welfare Organization of Hamadan province. Families were included a total of 60 patients (39 male and 21 female whose intellectual disability had been confirmed by Raven IQ test. Each family was asked for clinical examination and getting consent form. Blood sample was collected from each family. One proband from each family was tested for CGG repeat expansion in FMR1 gene, chromosomal abnormalities and inborn errors of metabolism. We also performed homozygosity mapping based on STR markers for seven known MCPH loci in families with primary microcephaly and AR-ID. Results: Five families had full mutation of Fragile X syndrome. No chromosomal abnormalities were identified. Metabolic screening revealed one family with Medium Chain Acyl CoA Dehydrogenase deficiency. None of three families with primary microcephaly and AR-ID showed linkage to any of known seven MCPH loci. Conclusion: The main causes of ID in Hamadan province were Fragile X syndrome and Autosomal Recessive Primary Microcephaly with the frequencies of 20% and 12%, respectively.

  3. Autosomal recessive ichthyosis with hypotrichosis syndrome: further delineation of the phenotype

    NARCIS (Netherlands)

    Avrahami, L.; Maas, S.; Pasmanik-Chor, M.; Rainshtein, L.; Magal, N.; Smitt, J. H. S.; van Marle, J.; Shohat, M.; Basel-Vanagaite, L.

    2008-01-01

    Autosomal recessive ichthyosis with hypotrichosis (ARIH) syndrome, which is characterized by congenital ichthyosis, abnormal hair and corneal involvement, has recently been shown in one consanguineous Israeli Arab family to be caused by a mutation in the ST14 gene, which encodes serine protease

  4. Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants.

    Science.gov (United States)

    Johnston, Jennifer J; van der Smagt, Jasper J; Rosenfeld, Jill A; Pagnamenta, Alistair T; Alswaid, Abdulrahman; Baker, Eva H; Blair, Edward; Borck, Guntram; Brinkmann, Julia; Craigen, William; Dung, Vu Chi; Emrick, Lisa; Everman, David B; van Gassen, Koen L; Gulsuner, Suleyman; Harr, Margaret H; Jain, Mahim; Kuechler, Alma; Leppig, Kathleen A; McDonald-McGinn, Donna M; Can, Ngoc Thi Bich; Peleg, Amir; Roeder, Elizabeth R; Rogers, R Curtis; Sagi-Dain, Lena; Sapp, Julie C; Schäffer, Alejandro A; Schanze, Denny; Stewart, Helen; Taylor, Jenny C; Verbeek, Nienke E; Walkiewicz, Magdalena A; Zackai, Elaine H; Zweier, Christiane; Zenker, Martin; Lee, Brendan; Biesecker, Leslie G

    2018-02-22

    PurposeTo characterize the molecular genetics of autosomal recessive Noonan syndrome.MethodsFamilies underwent phenotyping for features of Noonan syndrome in children and their parents. Two multiplex families underwent linkage analysis. Exome, genome, or multigene panel sequencing was used to identify variants. The molecular consequences of observed splice variants were evaluated by reverse-transcription polymerase chain reaction.ResultsTwelve families with a total of 23 affected children with features of Noonan syndrome were evaluated. The phenotypic range included mildly affected patients, but it was lethal in some, with cardiac disease and leukemia. All of the parents were unaffected. Linkage analysis using a recessive model supported a candidate region in chromosome 22q11, which includes LZTR1, previously shown to harbor mutations in patients with Noonan syndrome inherited in a dominant pattern. Sequencing analyses of 21 live-born patients and a stillbirth identified biallelic pathogenic variants in LZTR1, including putative loss-of-function, missense, and canonical and noncanonical splicing variants in the affected children, with heterozygous, clinically unaffected parents and heterozygous or normal genotypes in unaffected siblings.ConclusionThese clinical and genetic data confirm the existence of a form of Noonan syndrome that is inherited in an autosomal recessive pattern and identify biallelic mutations in LZTR1.Genet Med advance online publication, 22 February 2018; doi:10.1038/gim.2017.249.

  5. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy

    NARCIS (Netherlands)

    Lesage, S.; Drouet, V.; Majounie, E.; Deramecourt, V.; Jacoupy, M.; Nicolas, A.; Cormier-Dequaire, F.; Hassoun, S.M.; Pujol, C.; Ciura, S.; Erpapazoglou, Z.; Usenko, T.; Maurage, C.A.; Sahbatou, M.; Liebau, S.; Ding, J.; Bilgic, B.; Emre, M.; Erginel-Unaltuna, N.; Guven, G.; Tison, F.; Tranchant, C.; Vidailhet, M.; Corvol, J.C.; Krack, P.; Leutenegger, A.L.; Nalls, M.A.; Hernandez, D.G.; Heutink, P.; Gibbs, J.R.; Hardy, J.; Wood, N.W.; Gasser, T.; Durr, A.; Deleuze, J.F.; Tazir, M.; Destee, A.; Lohmann, E.; Kabashi, E.; Singleton, A.; Corti, O.; Brice, A.; Scheffer, H.; Bloem, B.R.; et al.,

    2016-01-01

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with

  6. Genetic Counselors' Experiences Regarding Communication of Reproductive Risks with Autosomal Recessive Conditions found on Cancer Panels.

    Science.gov (United States)

    Mets, Sarah; Tryon, Rebecca; Veach, Patricia McCarthy; Zierhut, Heather A

    2016-04-01

    The development of hereditary cancer genetic testing panels has altered genetic counseling practice. Mutations within certain genes on cancer panels pose not only a cancer risk, but also a reproductive risk for autosomal recessive conditions such as Fanconi anemia, constitutional mismatch repair deficiency syndrome, and ataxia telangiectasia. This study aimed to determine if genetic counselors discuss reproductive risks for autosomal recessive conditions associated with genes included on cancer panels, and if so, under what circumstances these risks are discussed. An on-line survey was emailed through the NSGC list-serv. The survey assessed 189 cancer genetic counselors' experiences discussing reproductive risks with patients at risk to carry a mutation or variant of uncertain significance (VUS) in a gene associated with both an autosomal dominant cancer risk and an autosomal recessive syndrome. Over half (n = 82, 55 %) reported having discussed reproductive risks; the remainder (n = 66, 45 %) had not. Genetic counselors who reported discussing reproductive risks primarily did so when patients had a positive result and were of reproductive age. Reasons for not discussing these risks included when a patient had completed childbearing or when a VUS was identified. Most counselors discussed reproductive risk after obtaining results and not during the informed consent process. There is inconsistency as to if and when the discussion of reproductive risks is taking place. The wide variation in responses suggests a need to develop professional guidelines for when and how discussions of reproductive risk for autosomal recessive conditions identified through cancer panels should occur with patients.

  7. Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool.

    Science.gov (United States)

    Hentschel, Julia; Tatun, Dana; Parkhomchuk, Dmitri; Kurth, Ingo; Schimmel, Bettina; Heinrich-Weltzien, Roswitha; Bertzbach, Sabine; Peters, Hartmut; Beetz, Christian

    2016-09-15

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X-linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations. Copyright © 2016. Published by Elsevier B.V.

  8. Microcephaly-chorioretinopathy syndrome, autosomal recessive form. A case report

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano Machado Rosa

    Full Text Available CONTEXT: The autosomal recessive form of microcephaly-chorioretinopathy syndrome is a rare genetic condition that is considered to be an important differential diagnosis with congenital toxoplasmosis.CASE REPORT: Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis. However, his serological tests for congenital infections, including toxoplasmosis, were negative. He was the first child of young, healthy and consanguineous parents (fourth-degree relatives. The parents had normal head circumferences and intelligence. The patient presented microcephaly and specific abnormalities of the retina, with multiple diffuse oval areas of pigmentation and patches of chorioretinal atrophy associated with diffuse pigmentation of the fundus. Ophthalmological evaluations on the parents were normal. A computed tomography scan of the child's head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications. We did not find any lymphedema in his hands and feet. He had postnatal growth retardation, severe mental retardation and cerebral palsy.CONCLUSIONS: The finding of chorioretinal lesions in a child with microcephaly should raise suspicions of the autosomal recessive form of microcephaly-chorioretinopathy syndrome, especially in cases with an atypical pattern of eye fundus and consanguinity. A specific diagnosis is essential for an appropriate clinical evaluation and for genetic counseling for the patients and their families.

  9. A novel NR2E3 gene mutation in autosomal recessive retinitis pigmentosa with cystic maculopathy

    OpenAIRE

    Mahajan, D.; Votruba, Marcela

    2017-01-01

    NR2E3 is a gene that encodes for photoreceptor cell specific nuclear receptor, which is involved in cone proliferation. The splice site mutation 119-2A>C in NR2E3 (15q23) has been previously reported to underlie recessive enhanced cone S sensitivity syndrome, clumped pigmentary retinal degeneration, Goldman-Favre syndrome and also autosomal dominant and autosomal recessive retinitis pigmentosa (RP). However, the mutation c 571 + 2 T > C in NR2E3 has not been previously reported with retinal d...

  10. Target gene analyses of 39 amelogenesis imperfecta kindreds

    Science.gov (United States)

    Chan, Hui-Chen; Estrella, Ninna M. R. P.; Milkovich, Rachel N.; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C-C.

    2012-01-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred. PMID:22243262

  11. Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

    Science.gov (United States)

    Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

    2018-01-30

    Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism.

    NARCIS (Netherlands)

    Rawal, N.; Periquet, M.; Lohmann, E.; Lucking, C.B.; Teive, H.; Ambrosio, G.; Raskin, S.; Lincoln, S.; Hattori, N.; Guimaraes, J.; Horstink, M.W.I.M.; Santos Bele, W. Dos; Brousolle, E.; Destee, A.; Mizuno, Y.; Farrer, M.; Deleuze, J.F.; Michele, G. de; Agid, Y.; Durr, A.; Brice, A.

    2003-01-01

    The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly

  13. A novel HSF4 gene mutation (p.R405X causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan

    Directory of Open Access Journals (Sweden)

    Cheema Abdul

    2008-11-01

    Full Text Available Abstract Background Hereditary cataracts are most frequently inherited as autosomal dominant traits, but can also be inherited in an autosomal recessive or X-linked fashion. To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene HSF4 (Genbank accession number NM_001040667. Here, we describe a family from Pakistan with the first nonsense mutation in HSF4 thus expanding the mutational spectrum of this heat shock transcription factor gene. Methods A large consanguineous Pakistani family with autosomal recessive cataracts was collected from Quetta. Genetic linkage analysis was performed for the common known autosomal recessive cataracts loci and linkage to a locus containing HSF4 (OMIM 602438 was found. All exons and adjacent splice sites of the heat shock transcription factor 4 gene (HSF4 were sequenced. A mutation-specific restriction enzyme digest (HphI was performed for all family members and unrelated controls. Results The disease phenotype perfectly co-segregated with markers flanking the known cataract gene HSF4, whereas other autosomal recessive loci were excluded. A maximum two-point LOD score with a Zmax = 5.6 at θ = 0 was obtained for D16S421. Direct sequencing of HSF4 revealed the nucleotide exchange c.1213C > T in this family predicting an arginine to stop codon exchange (p.R405X. Conclusion We identified the first nonsense mutation (p.R405X in exon 11 of HSF4 in a large consanguineous Pakistani family with autosomal recessive cataract.

  14. Congenital myotonic myopathy in the miniature schnauzer: an autosomal recessive trait.

    Science.gov (United States)

    Vite, C H; Melniczek, J; Patterson, D; Giger, U

    1999-01-01

    Myotonia is a clinical sign characterized by a delay in skeletal muscle relaxation following electrical or mechanical stimulation. A series of related miniature schnauzer dogs with congenital myotonic myopathy were studied. A composite pedigree of six affected litters and the results of a planned breeding between two affected animals are consistent with an autosomal recessive mode of inheritance.

  15. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

    Science.gov (United States)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas

    2013-03-07

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation

    International Nuclear Information System (INIS)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P.

    2006-01-01

    The chlorophyllin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin

  17. The absence of correlations between a clinical classification and ultrastructural findings in amelogenesis imperfecta

    International Nuclear Information System (INIS)

    Baeckman, B.; Lundgren, T.; Engstroem, E.U.; Falk, L.K.L.; Chabala, J.M.; Levi-Setti, R.; Noren, J.G.

    1993-01-01

    This study was performed to examine whether a clinical classification of different phenotypes of amelogenesis imperfecta could be discernible at the ultrastructural level. 17 primary teeth from 16 children with hypomineralization, hypomaturation, or hypoplastic variants of the disease were collected for histologic studies of the enamel by means of polarized light microscopy, scanning electron microscopy (SEM), and secondary ion mass spectrometry (SIMS). Polarization microscopy showed that the enamel was hypomineralized; in 6 teeth a wavy configuration of the enamel prisms also appeared. Three histomorphologic main types could be discerned. In 10 of the teeth extensive hypermineralization of the bulk of the enamel was found. 1 tooth had an unusually tick enamel with only a thin normally mineralized surface layer. SIMS images showed less pronounced signals from Ca 2+ and Na + , but with stronger signals from Cl - and CN - , representing the organic component of enamel. The SEM images showed an irregular prism pattern with marked interprismatic areas. Irrespective of the clinical appearance or the herediatary pattern the main findings were hypomineralized enamel with or without wavy bands. Neither of the analytical methods used in this paper distinguishes between the clinical phenotypes of amelogenesis imperfecta. 35 refs., 9 figs., 1 tab

  18. Enfermedad poliquística autosómica recesiva Recessive autosomal polycystic disease

    Directory of Open Access Journals (Sweden)

    Sandalio Durán Álvarez

    2007-06-01

    Full Text Available Como enfermedades renales poliquísticas hereditarias se describen clásicamente la autosómica recesiva y la autosómica dominante, mal llamadas enfermedad poliquística de tipo infantily de;tipo adulto, respectivamente, pues ambas pueden verse tanto en una como en otra edad. Los conceptos cambiantes en cuanto a la enfermedad autosómica recesiva, dados por los progresos en el tratamiento de los recién nacidos con la enfermedad, y la localización del gen, que por su mutación la produce, nos motivan hacer esta breve revisión con la finalidad de contribuir a la comprensión de la enfermedad por los estudiantes de medicina y el médico general básico.Recessive autosomal and dominant autosomal polycystic kidney diseases are classically described as hereditary illnesses; they are also called polycystic disease of child type” and of adult typerespectively since both may be seen in any of these two life stages. The changing concepts of recessive autosomal disease, given the advances made in the treatment of newborns with this disease, and the location of the gen, the mutation of which causes it, encouraged us to make a brief literature review to help medical students and general practitioners to understand this disease.

  19. Evidence for autosomal recessive inheritance in cerebral gigantism

    Science.gov (United States)

    Nevo, S.; Zeltzer, M.; Benderly, A.; Levy, J.

    1974-01-01

    Three cases of cerebral gigantism, two sibs and their double first cousin, are described in a large inbred family from Israel. Two of the three were observed and diagnosed at birth and two were followed for two years. They all presented the signs and symptoms considered typical of this syndrome, as well as some of the less frequent findings. Generalized oedema and flexion contractures of the feet were observed in two of the three at birth. This has not hitherto been reported in cases of cerebral gigantism, of whom only a few have been observed and diagnosed at birth. Autosomal recessive inheritance is clearly implied in this family. Images PMID:4841084

  20. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  1. Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4-Mb YAC contig on chromosome 4q11-q21

    Energy Technology Data Exchange (ETDEWEB)

    Kaerrman, C.; Holmgren, G.; Forsman, K. [Univ. Hospital, Umea (Sweden)]|[Univ. of Umea (Sweden)] [and others

    1997-01-15

    Amelogenesis imperfecta (Al) is a clinically and genetically heterogeneous group of inherited enamel defects. We recently mapped a locus for autosomal dominant local hypoplastic amelogenesis imperfecta (AIH2) to the long arm of chromosome 4. The disease gene was localized to a 17.6-cM region between the markers D4S392 and D4S395. The albumin gene (ALB), located in the same interval, was a candidate gene for autosomal dominant AI (ADAI) since albumin has a potential role in enamel maturation. Here we describe refined mapping of the AIH2 locus and the construction of marker maps by radiation hybrid mapping and yeast artificial chromosome (YAC)-based sequence tagged site-content mapping. A radiation hybrid map consisting of 11 microsatellite markers in the 5-cM interval between D4S409 and D4S1558 was constructed. Recombinant haplotypes in six Swedish ADAI families suggest that the disease gene is located in the interval between D4S2421 and ALB. ALB is therefore not likely to be the disease-causing gene. Affected members in all six families share the same allele haplotypes, indicating a common ancestral mutation in all families. The AIH2 critical region is less than 4 cM and spans a physical distance of approximately 4 Mb as judged from radiation hybrid maps. A YAC contig over the AIH2 critical region including several potential candidate genes was constructed. 35 refs., 4 figs., 1 tab.

  2. Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Smith, Claire El; Whitehouse, Laura LE; Poulter, James A; Brookes, Steven J; Day, Peter F; Soldani, Francesca; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2017-08-01

    We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T, p.(P249L)) in ACPT, the gene encoding acid phosphatase, testicular, which segregates with hypoplastic amelogenesis imperfecta in two unrelated families. ACPT is reported to play a role in odontoblast differentiation and mineralisation by supplying phosphate during dentine formation. Analysis by computerised tomography and scanning electron microscopy of a primary molar tooth from an individual homozygous for the c.746C>T variant revealed an enamel layer that was hypoplastic, but mineralised with prismatic architecture. These findings implicate variants in ACPT as a cause of early failure of amelogenesis during the secretory phase.

  3. Novel CLCN7 compound heterozygous mutations in intermediate autosomal recessive osteopetrosis.

    Science.gov (United States)

    Okamoto, Nana; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Komori, Takahide; Imoto, Issei

    2017-01-01

    Osteopetrosis is a heritable disorder of the skeleton that is characterized by increased bone density on radiographs caused by defects in osteoclast formation and function. Mutations in >10 genes are identified as causative for this clinically and genetically heterogeneous disease in humans. We report two novel missense variations in a compound heterozygous state in the CLCN7 gene, detected through targeted exome sequencing, in a 15-year-old Japanese female with intermediate autosomal recessive osteopetrosis.

  4. Hereditary motor and sensory neuropathy-russe: new autosomal recessive neuropathy in Balkan Gypsies.

    Science.gov (United States)

    Thomas, P K; Kalaydjieva, L; Youl, B; Rogers, T; Angelicheva, D; King, R H; Guergueltcheva, V; Colomer, J; Lupu, C; Corches, A; Popa, G; Merlini, L; Shmarov, A; Muddle, J R; Nourallah, M; Tournev, I

    2001-10-01

    A novel peripheral neuropathy of autosomal recessive inheritance has been identified in Balkan Gypsies and termed hereditary motor and sensory neuropathy-Russe (HMSN-R). We investigated 21 affected individuals from 10 families. Distal lower limb weakness began between the ages of 8 and 16 years, upper limb involvement beginning between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in two instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. HMSN-R is a new form of autosomal recessive inherited HMSN caused by a single founder mutation in a 1 Mb interval on chromosome 10q.

  5. The absence of correlations between a clinical classification and ultrastructural findings in amelogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Baeckman, B.; Lundgren, T.; Engstroem, E.U.; Falk, L.K.L.; Chabala, J.M.; Levi-Setti, R.; Noren, J.G. (Dept. of Pedodontics, Univ. of Goeteborg (Sweden))

    1993-01-01

    This study was performed to examine whether a clinical classification of different phenotypes of amelogenesis imperfecta could be discernible at the ultrastructural level. 17 primary teeth from 16 children with hypomineralization, hypomaturation, or hypoplastic variants of the disease were collected for histologic studies of the enamel by means of polarized light microscopy, scanning electron microscopy (SEM), and secondary ion mass spectrometry (SIMS). Polarization microscopy showed that the enamel was hypomineralized; in 6 teeth a wavy configuration of the enamel prisms also appeared. Three histomorphologic main types could be discerned. In 10 of the teeth extensive hypermineralization of the bulk of the enamel was found. 1 tooth had an unusually tick enamel with only a thin normally mineralized surface layer. SIMS images showed less pronounced signals from Ca[sup 2+] and Na[sup +], but with stronger signals from Cl[sup -] and CN[sup -], representing the organic component of enamel. The SEM images showed an irregular prism pattern with marked interprismatic areas. Irrespective of the clinical appearance or the herediatary pattern the main findings were hypomineralized enamel with or without wavy bands. Neither of the analytical methods used in this paper distinguishes between the clinical phenotypes of amelogenesis imperfecta. 35 refs., 9 figs., 1 tab.

  6. Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.

    Science.gov (United States)

    Thedrez, Aurélie; Sjouke, Barbara; Passard, Maxime; Prampart-Fauvet, Simon; Guédon, Alexis; Croyal, Mikael; Dallinga-Thie, Geesje; Peter, Jorge; Blom, Dirk; Ciccarese, Milco; Cefalù, Angelo B; Pisciotta, Livia; Santos, Raul D; Averna, Maurizio; Raal, Frederick; Pintus, Paolo; Cossu, Maria; Hovingh, Kees; Lambert, Gilles

    2016-08-01

    Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured by flow cytometry and confocal microscopy was higher in ARH than in control lymphocytes. PCSK9 significantly reduced LDL receptor expression in ARH lymphocytes albeit to a lower extent than in control lymphocytes (25% versus 76%, respectively), an effect reversed by alirocumab. Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes. PCSK9 significantly lowered LDL cellular uptake in ARH lymphocytes, on average by 18%, compared with a 46% reduction observed in control lymphocytes, an effect also reversed by alirocumab. Overall, the effects of recombinant PCSK9, and hence of alirocumab, on LDL receptor expression and function were significantly less pronounced in ARH than in control cells. PCSK9 inhibition with alirocumab on top of statin treatment has the potential to lower LDL cholesterol in some autosomal recessive hypercholesterolemia patients. © 2016 American Heart Association, Inc.

  7. [Genetic study of the autosomal recessive form of Charcot-Marie-Tooth in an Algerian family].

    Science.gov (United States)

    Hamadouche, T; Tazir-Melboucy, M; Benhassine, T

    1998-01-01

    Charcot-Marie-Tooth disease (CMT) is a hereditary neuropathy characterized by muscular atrophy and progressive sensitive alterations that affect limbs. The CMT is one of the most heterogenous diseases, clinically as well as genetically. At least twelve loci are responsible for the CMT phenotype, four of them for the autosomal recessive form. The aim of our work was to determinate the implication/exclusion of these four loci in an Algerian family by linkage analysis using microsatellites markers. We have tested the four loci on 8q13-21.1 (CMT4A), 11q23 (CMT4B), 5q23-33 (CMT4C) 8q24 (CMTAR). The haplotype reconstruction allowed us to exclude all the loci in this family, suggesting that the locus (gene) responsible for this form of CMT is localized elsewhere in the genome, thus providing an other observation of the great heterogeneity of the CMT, particularly autosomal recessive.

  8. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    Science.gov (United States)

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

    2012-01-01

    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  9. Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease.

    NARCIS (Netherlands)

    Ijzer, Suzanne; Born, L.I. van den; Zonneveld, M.N.; Lopez, I.; Ayyagari, R.; Teye-Botchway, L.; Mota-Vieira, L.; Cremers, F.P.M.; Koenekoop, R.K.

    2007-01-01

    PURPOSE: To identify the causative gene mutations in three siblings with severe progressive autosomal recessive cone-rod dystrophy (arCRD) and their fifth paternal cousin with Stargardt disease (STGD1) and to specify the phenotypes. METHODS: We evaluated eight sibs of one family, three family

  10. Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.

    Directory of Open Access Journals (Sweden)

    Dirk J Lefeber

    2011-12-01

    Full Text Available Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart failure, especially in young children. Here, we describe 11 young patients (5-13 years with a predominant presentation of dilated cardiomyopathy (DCM. Metabolic investigations showed deficient protein N-glycosylation, leading to a diagnosis of Congenital Disorders of Glycosylation (CDG. Homozygosity mapping in the consanguineous families showed a locus with two known genes in the N-glycosylation pathway. In all individuals, pathogenic mutations were identified in DOLK, encoding the dolichol kinase responsible for formation of dolichol-phosphate. Enzyme analysis in patients' fibroblasts confirmed a dolichol kinase deficiency in all families. In comparison with the generally multisystem presentation in CDG, the nonsyndromic DCM in several individuals was remarkable. Investigation of other dolichol-phosphate dependent glycosylation pathways in biopsied heart tissue indicated reduced O-mannosylation of alpha-dystroglycan with concomitant functional loss of its laminin-binding capacity, which has been linked to DCM. We thus identified a combined deficiency of protein N-glycosylation and alpha-dystroglycan O-mannosylation in patients with nonsyndromic DCM due to autosomal recessive DOLK mutations.

  11. A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs.

    Directory of Open Access Journals (Sweden)

    Margret L Casal

    Full Text Available Autosomal recessive congenital ichthyosis in the American bulldog is characterized by generalized scaling and erythema with adherent scale on the glabrous skin. We had previously linked this disorder to NIPAL4, which encodes the protein ichthyin. Sequencing of NIPAL4 revealed a homozygous single base deletion (CanFam3.1 canine reference genome sequence NC_06586.3 g.52737379del, the 157th base (cytosine in exon 6 of NIPAL4 as the most likely causative variant in affected dogs. This frameshift deletion results in a premature stop codon producing a truncated and defective NIPAL4 (ichthyin protein of 248 amino acids instead of the wild-type length of 404. Obligate carriers were confirmed to be heterozygous for this variant, and 150 clinically non-affected dogs of other breeds were homozygous for the wild-type gene. Among 800 American bulldogs tested, 34% of clinically healthy dogs were discovered to be heterozygous for the defective allele. More importantly, the development of this canine model of autosomal recessive congenital ichthyosis will provide insight into the development of new treatments across species.

  12. Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI).

    Science.gov (United States)

    Masuya, Hiroshi; Shimizu, Kunihiko; Sezutsu, Hideki; Sakuraba, Yoshiyuki; Nagano, Junko; Shimizu, Aya; Fujimoto, Naomi; Kawai, Akiko; Miura, Ikuo; Kaneda, Hideki; Kobayashi, Kimio; Ishijima, Junko; Maeda, Takahide; Gondo, Yoichi; Noda, Tetsuo; Wakana, Shigeharu; Shiroishi, Toshihiko

    2005-03-01

    Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.

  13. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Beggs, A.H.; Neumann, P.E.; Anderson, M.S.; Kunkel, L.M. (Harvard Medical School, Boston, MA (United States)); Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya (National Inst. of Neuroscience, Tokyo (Japan))

    1992-01-15

    Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.

  14. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.

    Science.gov (United States)

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A; Hernandez, Dena G; Heutink, Peter; Gibbs, J Raphael; Hardy, John; Wood, Nicholas W; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis

    2016-03-03

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Ek, Jakob; Sand, Annie

    2009-01-01

    PURPOSE: The study was initiated to investigate the mutation spectrum of four OCA genes and to calculate the birth prevalence in patients with autosomal recessive albinism. METHODS: Mutation analysis using dHPLC or direct DNA sequencing of TYR, OCA2, TYRP1, and MATP was performed in 62 patients....... Two mutations in one OCA gene explained oculocutaneous albinism (OCA) in 44% of the patients. Mutations in TYR were found in 26% of patients, while OCA2 and MATP caused OCA in 15% and 3%, respectively. No mutations were found in TYRP1. Of the remaining 56% of patients, 29% were heterozygous...... for a mutation in either TYR or OCA2, and 27% were without mutations in any of the four genes. Exclusive expression of the mutant allele was found in four heterozygous patients. A minimum birth prevalence of 1 in 14,000 was calculated, based on register data on 218 patients. The proportion of OCA to autosomal...

  16. Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel

    DEFF Research Database (Denmark)

    Rehman, Shoaib ur; Baig, Shahid Mahmood; Eiberg, Hans

    2011-01-01

    done in all sampled individuals in the family. The nuclear central loop in the five generation family showed homozygosity for a 6-Mb telomeric region on 11p15, whereas all other linkage regions were excluded by calculation of logarithm of odds (LOD) for the SNP microarray data. A maximum LOD score of Z......Autosomal recessive inherited mental retardation is an extremely heterogeneous disease and accounts for approximately 25% of all non-syndromic mental retardation cases. Autozygosity mapping of a large consanguineous Pakistani family revealed a novel locus for non-syndromic autosomal recessive...

  17. Novel compound heterozygous MYO7A mutations in Moroccan families with autosomal recessive non-syndromic hearing loss.

    Directory of Open Access Journals (Sweden)

    Amina Bakhchane

    Full Text Available The MYO7A gene encodes a protein belonging to the unconventional myosin super family. Mutations within MYO7A can lead to either non syndromic hearing loss or to the Usher syndrome type 1B (USH1B. Here, we report the results of genetic analyses performed on Moroccan families with autosomal recessive non syndromic hearing loss that identified two families with compound heterozygous MYO7A mutations. Five mutations (c.6025delG, c.6229T>A, c.3500T>A, c.5617C>T and c.4487C>A were identified in these families, the latter presenting two differently affected branches. Multiple bioinformatics programs and molecular modelling predicted the pathogenic effect of these mutations. In conclusion, the absence of vestibular and retinal symptom in the affected patients suggests that these families have the isolated non-syndromic hearing loss DFNB2 (nonsyndromic autosomal recessive hearing loss presentation, instead of USH1B.

  18. Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum

    Science.gov (United States)

    2011-01-01

    Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder. PMID:21668957

  19. Identification of Mutations in SDR9C7 in 6 Families with Autosomal Recessive Congenital Ichthyosis

    DEFF Research Database (Denmark)

    Hotz, A; Fagerberg, C; Vahlquist, A

    2018-01-01

    Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization. To date, ARCI has been associated with following genes: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, TGM1, PNPLA1 and recently SDR9C7 and SULT2B1.(1-6) Furthermore, seven patients from...

  20. A Fourth KLK4 Mutation Is Associated with Enamel Hypomineralisation and Structural Abnormalities

    Directory of Open Access Journals (Sweden)

    Claire E. L. Smith

    2017-05-01

    Full Text Available “Amelogenesis imperfecta” (AI describes a group of genetic conditions that result in defects in tooth enamel formation. Mutations in many genes are known to cause AI, including the gene encoding the serine protease, kallikrein related peptidase 4 (KLK4, expressed during the maturation stage of amelogenesis. In this study we report the fourth KLK4 mutation to be identified in autosomal recessively-inherited hypomaturation type AI, c.632delT, p.(L211Rfs*37 (NM_004917.4, NP_004908.4. This homozygous variant was identified in five Pakistani AI families and is predicted to result in a transcript with a premature stop codon that escapes nonsense mediated decay. However, the protein may misfold, as three of six disulphide bonds would be disrupted, and may be degraded or non-functional as a result. Primary teeth were obtained from one affected individual. The enamel phenotype was characterized using high-resolution computerized X-ray tomography (CT, scanning electron microscopy (SEM, energy dispersive X-ray spectroscopy (EDX, and microhardness testing (MH. Enamel from the affected individual (referred to as KLK4 enamel was hypomineralised in comparison with matched control enamel. Furthermore, KLK4 inner enamel was hypomineralised compared with KLK4 outer enamel. SEM showed a clear structural demarcation between KLK4 inner and outer enamel, although enamel structure was similar to control tissue overall. EDX showed that KLK4 inner enamel contained less calcium and phosphorus and more nitrogen than control inner enamel and KLK4 outer enamel. MH testing showed that KLK4 inner enamel was significantly softer than KLK4 outer enamel (p < 0.001. However, the hardness of control inner enamel was not significantly different to that of control outer enamel. Overall, these findings suggest that the KLK4 c.632delT mutation may be a common cause of autosomal recessive AI in the Pakistani population. The phenotype data obtained mirror findings in the Klk4

  1. Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone- shaped epiphyses in hands and hips

    NARCIS (Netherlands)

    Hellemans, J; Coucke, PJ; Giedion, A; De Paepe, A; Kramer, P; Beemer, F; Mortier, GR

    Acrocapitofemoral dysplasia is a recently delineated autosomal recessive skeletal dysplasia, characterized clinically by short stature with short limbs and radiographically by cone-shaped epiphyses, mainly in hands and hips. Genome-wide homozygosity mapping in two consanguineous families linked the

  2. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

    DEFF Research Database (Denmark)

    Bultmann-Mellin, Insa; Conradi, Anne; Maul, Alexandra C

    2015-01-01

    Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been ...

  3. Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia

    DEFF Research Database (Denmark)

    Hellström Pigg, Maritta; Bygum, Anette; Gånemo, Agneta

    2016-01-01

    Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic...... ichthyosis (PI), characterized by marked skin changes at birth and subsequently mild symptoms. In nationwide screenings of suspected cases of ARCI in Denmark and Sweden, we identified 132 patients (age range 0.1-86 years) classified as HI (n = 7), LI (n = 70), CIE (n = 17) and PI (n = 38). At birth......-100%). A scoring (0-4) of ichthyosis/ery-thema past infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n = 8), ALOXE3 (n = 9), SLC27...

  4. Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan

    OpenAIRE

    Ansar, Muhammad; Ramzan, Mohammad; Pham, Thanh L.; Yan, Kai; Jamal, Syed Muhammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

    2003-01-01

    For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod...

  5. The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice

    Science.gov (United States)

    van Huet, Ramon A. C.; Pierrache, Laurence H.M.; Meester-Smoor, Magda A.; Klaver, Caroline C.W.; van den Born, L. Ingeborgh; Hoyng, Carel B.; de Wijs, Ilse J.; Collin, Rob W. J.; Hoefsloot, Lies H.

    2015-01-01

    Purpose To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). Methods We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon–intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. Results The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). Conclusions The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis. PMID:25999674

  6. Pregnancy in autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Banks, Nicole; Bryant, Joy; Fischer, Roxanne; Huizing, Marjan; Gahl, William A; Gunay-Aygun, Meral

    2015-03-01

    Autosomal recessive polycystic kidney disease (ARPKD) is the most common childhood-onset ciliopathy. As treatments improve, more women are reaching reproductive age, but little is known about ARPKD and pregnancy. In our ongoing study on ARPKD and other ciliopathies, 12 females over 18 years of age were identified and systematically evaluated. Six had children; four carried pregnancies and delivered, one used assisted reproductive technology and had a surrogate carry the pregnancy, and one adopted. We report the outcomes of four pregnancies with live birth deliveries and two women who chose alternate family building options. Patient one was diagnosed at 6 months, and at age 21 had a pregnancy complicated by transient worsening of renal function (creatinine increase from 1.15 to 1.78 mg/dL). Patient two was diagnosed with ARPKD at age seven and had an uncomplicated pregnancy at age 23. Patient three was diagnosed incidentally with ARPKD at age 23, 3 months after completion of an uncomplicated pregnancy. Patient four who had an uncomplicated pregnancy at age 33 was diagnosed with ARPKD at age 46. Women with ARPKD face reproductive decisions largely bereft of information about the pregnancies of other ARPKD patients. We report four cases of pregnancy and ARPKD to expand current knowledge and encourage further research.

  7. A Novel Mutation in the Transglutaminase-1 Gene in an Autosomal Recessive Congenital Ichthyosis Patient

    Directory of Open Access Journals (Sweden)

    D. Vaigundan

    2014-01-01

    Full Text Available Structure-function implication on a novel homozygous Trp250/Gly mutation of transglutaminase-1 (TGM1 observed in a patient of autosomal recessive congenital ichthyosis is invoked from a bioinformatics analysis. Structural consequences of this mutation are hypothesized in comparison to homologous enzyme human factor XIIIA accepted as valid in similar structural analysis and are projected as guidelines for future studies at an experimental level on TGM1 thus mutated.

  8. Macroepiphyseal dysplasia with symptomatic osteoporosis, wrinkled skin, and aged appearance: A presumed autosomal recessive condition

    Energy Technology Data Exchange (ETDEWEB)

    McAlister, W.H.; Coe, J.D.; Whyte, M.P.

    1986-01-01

    We report our detailed investigation of a 7-1/2-year-old girl with short stature, aged appearance, decreased subcutaneous fat and muscle mass, dry coarse hair, foot deformities, macroepiphyses with prominent but lax joints, and osteoporosis with recurrent fractures who is the offspring of first cousins. This constellation of abnormalities differs from previously reported cases where macroepiphyses were a prominent finding. Our patient appears, therefore, to have a new, autosomal recessively inherited, syndrome.

  9. Macroepiphyseal dysplasia with symptomatic osteoporosis, wrinkled skin, and aged appearance: A presumed autosomal recessive condition

    International Nuclear Information System (INIS)

    McAlister, W.H.; Coe, J.D.; Whyte, M.P.; Shriners Hospital for Crippled Children, St. Louis, MO

    1986-01-01

    We report our detailed investigation of a 7-1/2-year-old girl with short stature, aged appearance, decreased subcutaneous fat and muscle mass, dry coarse hair, foot deformities, macroepiphyses with prominent but lax joints, and osteoporosis with recurrent fractures who is the offspring of first cousins. This constellation of abnormalities differs from previously reported cases where macroepiphyses were a prominent finding. Our patient appears, therefore, to have a new, autosomal recessively inherited, syndrome. (orig.)

  10. Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

    NARCIS (Netherlands)

    Gostynska, Katarzyna B.; Yuen, Wing Yan; Pasmooij, Anna Maria Gerdina; Stellingsma, Cornelius; Pas, Hendri H.; Lemmink, Henny; Jonkman, Marcel F.

    2017-01-01

    The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin

  11. The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation.

    Science.gov (United States)

    Basel-Vanagaite, L; Attia, R; Yahav, M; Ferland, R J; Anteki, L; Walsh, C A; Olender, T; Straussberg, R; Magal, N; Taub, E; Drasinover, V; Alkelai, A; Bercovich, D; Rechavi, G; Simon, A J; Shohat, M

    2006-03-01

    The molecular basis of autosomal recessive non-syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family. To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12. The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I-kappaB kinase/NFkappaB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus. A previously unknown signal transduction pathway is important in human cognitive development.

  12. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

    OpenAIRE

    Iqbal, Zafar; P?ttmann, Lucia; Musante, Luciana; Razzaq, Attia; Zahoor, Muhammad Yasir; Hu, Hao; Wienker, Thomas F; Garshasbi, Masoud; Fattahi, Zohreh; Gilissen, Christian; Vissers, Lisenka ELM; de Brouwer, Arjan PM; Veltman, Joris A; Pfundt, Rolph; Najmabadi, Hossein

    2015-01-01

    AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenti...

  13. A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability

    OpenAIRE

    Larti, Farzaneh; Kahrizi, Kimia; Musante, Luciana; Hu, Hao; Papari, Elahe; Fattahi, Zohreh; Bazazzadegan, Niloofar; Liu, Zhe; Banan, Mehdi; Garshasbi, Masoud; Wienker, Thomas F; Hilger Ropers, H; Galjart, Niels; Najmabadi, Hossein

    2015-01-01

    In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score=3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which ...

  14. Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

    NARCIS (Netherlands)

    Klevering, B.J.; Ijzer, S.; Rohrschneider, K.; Zonneveld-Vrieling, M.N.; Allikmets, R.; Born, L.I. van den; Maugeri, A.; Hoyng, C.B.; Cremers, F.P.M.

    2004-01-01

    Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or

  15. Clinical and genetic characteristics of autosomal recessive axonal neuropathy with neuromyotonia in Russian patients

    Directory of Open Access Journals (Sweden)

    E. L. Dadali

    2017-01-01

    Full Text Available Introduction. Hereditary motor and sensory neuropathies are genetically heterogeneous group of disorders characterized by a progressive muscle weakness, atrophy of hand and leg muscles often associated with deformations, and mild to moderate sensory loss. Axonal neuropathy with neuromyotonia (AR-ANM is one of the rarest autosomal recessive hereditary neuropathies. Materials and methods. Six (6 patients (4 men, 2 women aged 14–40 years from unrelated families with suspicion of HMSN were examined clinically, neurophysiologically and using DNA analysis. Results. Neurophysiological examination revealed motor and sensory neuropathy with neuromyotonia signs in all patients. In all cases homozygous variant of recessive mutations с.110G/C (р.Arg37Pro in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1 has been revealed. Conclusion. There is the first description of the clinical and neurophysiological features of six patients with AR-ANM in Russia. 

  16. Mutation in LIM2 Is Responsible for Autosomal Recessive Congenital Cataracts.

    Directory of Open Access Journals (Sweden)

    Bushra Irum

    Full Text Available To identify the molecular basis of non-syndromic autosomal recessive congenital cataracts (arCC in a consanguineous family.All family members participating in the study received a comprehensive ophthalmic examination to determine their ocular phenotype and contributed a blood sample, from which genomic DNA was extracted. Available medical records and interviews with the family were used to compile the medical history of the family. The symptomatic history of the individuals exhibiting cataracts was confirmed by slit-lamp biomicroscopy. A genome-wide linkage analysis was performed to localize the disease interval. The candidate gene, LIM2 (lens intrinsic membrane protein 2, was sequenced bi-directionally to identify the disease-causing mutation. The physical changes caused by the mutation were analyzed in silico through homology modeling, mutation and bioinformatic algorithms, and evolutionary conservation databases. The physiological importance of LIM2 to ocular development was assessed in vivo by real-time expression analysis of Lim2 in a mouse model.Ophthalmic examination confirmed the diagnosis of nuclear cataracts in the affected members of the family; the inheritance pattern and cataract development in early infancy indicated arCC. Genome-wide linkage analysis localized the critical interval to chromosome 19q with a two-point logarithm of odds (LOD score of 3.25. Bidirectional sequencing identified a novel missense mutation, c.233G>A (p.G78D in LIM2. This mutation segregated with the disease phenotype and was absent in 192 ethnically matched control chromosomes. In silico analysis predicted lower hydropathicity and hydrophobicity but higher polarity of the mutant LIM2-encoded protein (MP19 compared to the wild-type. Moreover, these analyses predicted that the mutation would disrupt the secondary structure of a transmembrane domain of MP19. The expression of Lim2, which was detected in the mouse lens as early as embryonic day 15 (E15

  17. Congenital non-syndromal autosomal recessive deafness in Bengkala, an isolated Balinese village.

    Science.gov (United States)

    Winata, S; Arhya, I N; Moeljopawiro, S; Hinnant, J T; Liang, Y; Friedman, T B; Asher, J H

    1995-01-01

    Bengkala is an Indonesian village located on the north shore of Bali that has existed for over 700 years. Currently, 2.2% of the 2185 people in this village have profound congenital deafness. In response to the high incidence of deafness, the people of Bengkala have developed a village specific sign language which is used by many of the hearing and deaf people. Deafness in Bengkala is congenital, sensorineural, non-syndromal, and caused by a fully penetrant autosomal recessive mutation at the DFNB3 locus. The frequency of the DFNB3 mutation is estimated to be 9.4% among hearing people who have a 17.2% chance of being heterozygous for DFNB3. PMID:7616538

  18. Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

    Science.gov (United States)

    Klevering, B Jeroen; Blankenagel, Anita; Maugeri, Alessandra; Cremers, Frans P M; Hoyng, Carel B; Rohrschneider, Klaus

    2002-06-01

    To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were reviewed after molecular analysis revealed mutations in the ABCA4 gene. In two of the patients both the photopic and scotopic electroretinogram were nonrecordable. In the remainder, the photopic cone b-wave amplitudes appeared to be more seriously affected than the scotopic rod b-wave amplitudes. Although the clinical presentation was heterogeneous, all patients experienced visual loss early in life, impaired color vision, and a central scotoma. Fundoscopy revealed evidence of early-onset maculopathy, sometimes accompanied by involvement of the retinal periphery in the later stages of the disease. Mutations in the ABCA4 gene are the pathologic cause of the CRD-like dystrophy in these patients, and the resultant clinical pictures are complex and heterogeneous. Given this wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.

  19. Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family.

    Science.gov (United States)

    Ma, Yalin; Xiao, Yun; Zhang, Fengguo; Han, Yuechen; Li, Jianfeng; Xu, Lei; Bai, Xiaohui; Wang, Haibo

    2016-04-01

    Mutations in MYO7A gene have been reported to be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Most mutations in MYO7A gene caused USH1B, whereas only a few reported mutations led to DFNB2 and DFNA11. The current study was designed to investigate the mutations among a Chinese family with autosomal recessive hearing loss. In this study, we present the clinical, genetic and molecular characteristics of a Chinese family. Targeted capture of 127 known deafness genes and next-generation sequencing were employed to study the genetic causes of two siblings in the Chinese family. Sanger sequencing was employed to examine those variant mutations in the members of this family and other ethnicity-matched controls. We identified the novel compound heterozygous mutant alleles of MYO7A gene: a novel missense mutation c.3671C>A (p.A1224D) and a reported insert mutation c.390_391insC (p.P131PfsX9). Variants were further confirmed by Sanger sequencing. These two compound heterozygous variants were co-segregated with autosomal recessive hearing loss phenotype. The gene mutation analysis and protein sequence alignment further supported that the novel compound heterozygous mutations were pathogenic. The novel compound heterozygous mutations (c.3671C>A and c.390_391insC) in MYO7A gene identified in this study were responsible for the autosomal recessive sensorineural hearing loss of this Chinese family. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. KohlschutterTonz Syndrome : Mutations in ROGDI and Evidence of Genetic Heterogeneity

    NARCIS (Netherlands)

    Tucci, Arianna; Kara, Eleanna; Schossig, Anna; Wolf, Nicole I.; Plagnol, Vincent; Fawcett, Katherine; Paisan-Ruiz, Coro; Moore, Matthew; Hernandez, Dena; Musumeci, Sebastiano; Tennison, Michael; Hennekam, Raoul; Palmeri, Silvia; Malandrini, Alessandro; Raskin, Salmo; Donnai, Dian; Hennig, Corina; Tzschach, Andreas; Hordijk, Roel; Bast, Thomas; Wimmer, Katharina; Lo, Chien-Ning; Shorvon, Simon; Mefford, Heather; Eichler, Evan E.; Hall, Roger; Hayes, Ian; Hardy, John; Singleton, Andrew; Zschocke, Johannes; Houlden, Henry

    KohlschutterTonz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschutter in 1974, and to date,

  1. The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non‐syndromic mental retardation

    Science.gov (United States)

    Basel‐Vanagaite, L; Attia, R; Yahav, M; Ferland, R J; Anteki, L; Walsh, C A; Olender, T; Straussberg, R; Magal, N; Taub, E; Drasinover, V; Alkelai, A; Bercovich, D; Rechavi, G; Simon, A J; Shohat, M

    2006-01-01

    Background The molecular basis of autosomal recessive non‐syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family. Objective To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12. Results The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I‐κB kinase/NFκB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus. Conclusions A previously unknown signal transduction pathway is important in human cognitive development. PMID:16033914

  2. SACS gene-related autosomal recessive spastic ataxia of Charlevoix-Saguenay from South India

    Directory of Open Access Journals (Sweden)

    M Suraj Menon

    2016-01-01

    Full Text Available Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS is a neurodegenerative disorder characterized by late infantile onset spastic ataxia and other neurological features. Initially described in the Charlevoix-Saguenay region of Quebec, Canada, it is being increasingly reported from many other countries. Here, we present the case of a 20-year-old male from South India, who presented with progressive ataxia, spasticity, and peripheral neuropathy with imaging features and genetic testing suggestive of SACS gene-related ARSACS. The phenotypic variability from other cases and occurrence in a geographically distinct region is stressed upon to alert the clinicians to consider ARSACS in progressive ataxias.

  3. Autosomal-dominant osteopetrosis: An incidental finding

    Directory of Open Access Journals (Sweden)

    Rajathi Maria

    2010-01-01

    Full Text Available Osteopetrosis is a descriptive term that refers to a group of rare, heritable disorders of the skeleton. Osteopetrotic conditions vary greatly in their presentation and severity, from just as an incidental finding on radiographs to causing life-threatening complications such as bone marrow suppression. It is caused by failure of osteoclast development and function. Osteopetrosis can be inherited as autosomal-recessive, autosomal-dominant or as X-linked traits, with the most severe forms being the autosomal-recessive ones. The severity of the disease is mild to moderate in the autosomal-dominant forms, with normal life expectancy. Diagnosis is largely based on clinical and radiographic evaluation. The present paper reports a case of autosomal-dominant osteopetrosis complicated by osteomyelitis with a short review of the condition.

  4. Genetics Home Reference: amelogenesis imperfecta

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Amelogenesis imperfecta Amelogenesis imperfecta Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Amelogenesis imperfecta is a disorder of tooth development. This ...

  5. A Challenging Case of Hepatoblastoma Concomitant with Autosomal Recessive Polycystic Kidney Disease and Caroli Syndrome—Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nevil Kadakia

    2017-06-01

    Full Text Available We report a rare case of an 18-month-old female with autosomal recessive polycystic kidney disease, Caroli syndrome, and pure fetal type hepatoblastoma. The liver tumor was surgically resected with no chemotherapy given. Now 9 years post resection she demonstrates no local or distant recurrence and stable renal function.

  6. A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa

    NARCIS (Netherlands)

    Van Schil, Kristof; Klevering, B. Jeroen; Leroy, Bart P.; Pott, Jan Willem R.; Bandah-Rozenfeld, Dikla; Zonneveld-Vrieling, Marijke N.; Sharon, Dror; den Hollander, Anneke I.; Cremers, Frans P. M.; De Baere, Elfride; Collin, Rob W. J.; van den Born, L. Ingeborgh

    PURPOSE. To identify mutations in FAM161A underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch and Belgian populations and to investigate whether common FAM161A-associated phenotypic features could be identified. METHODS. Homozygosity mapping, amplification-refractory mutation

  7. Mutations in ROGDI Cause Kohlschutter-Tonz Syndrome

    NARCIS (Netherlands)

    Schossig, A.; Wolf, N.I.; Fischer, C.; Fischer, M.; Stocker, G.; Pabinger, S.; Dander, A.; Steiner, B.; Tonz, O.; Kotzot, D.; Haberlandt, E.; Amberger, A.; Burwinkel, B.; Wimmer, K.; Fauth, C.; Grond-Ginsbach, C.; Koch, M.J.; Deichmann, A.; von Kalle, C.; Bartram, C.R.; Kohlschutter, A.; Trajanoski, Z.; Zschocke, J.

    2012-01-01

    Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of

  8. Fine mapping of the autosomal recessive retinitis pigmentosa locus (RP12) on chromosome 1q; exclusion of the phosducin gene (PDC)

    NARCIS (Netherlands)

    van Soest, S.; te Nijenhuis, S.; van den Born, L. I.; Bleeker-Wagemakers, E. M.; Sharp, E.; Sandkuijl, L. A.; Westerveld, A.; Bergen, A. A.

    1996-01-01

    In a previous study on a large pedigree from a genetically isolated population in the Netherlands, we localized a gene for autosomal recessive retinitis pigmentosa with paraarteriolar preservation of the retinal pigment epithelium (PPRPE) on the long arm of chromosome 1. In this study, we present an

  9. Molecular diagnostic in two families affected with Autosomic Recessive Pigmentary Retinitis

    International Nuclear Information System (INIS)

    Leal Esquivel, A.

    1996-01-01

    This study included two Costa Rican families with members affected by Recessive Pigmentary Autosomic Retinitis (RPAR). The first family (C1) from the province of San Jose, has 10 alive affected members, and 14 obligatory carriers. They present an Early Appearance Degeneration, RPAR tipe1 (cane-cone). The author used polymorphic markers (STRPs) to discard some related regions, with the RP in the literature. He also used the Linkage program, for the analysis of ligaments. The second family (P1), proceeding from Acosta (situated in the province of Alajuela), has 13 alive affected members and 23 obligatory carriers and they present numerous consanguineous unions. This case is a RPAR with Early Appearance (Night Blindness, fat ERG), but with a shower degeneration. The author concludes that, with studies such as this one, there will be a capacity to offer RP molecular diagnostic, and also advance in its knowledge and treatment. (S. Grainger)

  10. Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report.

    Science.gov (United States)

    Maghami, Fatemeh; Tabei, Seyed Mohammad Bagher; Moravej, Hossein; Dastsooz, Hassan; Modarresi, Farzaneh; Silawi, Mohammad; Faghihi, Mohammad Ali

    2018-05-25

    Osteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance. Here we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A > G, IVS7-2A > G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation. Our study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations.

  11. A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Zamba-Papanicolaou Eleni

    2008-04-01

    Full Text Available Abstract Background Senataxin (chromosome 9q34 was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA, termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2 and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP. Here, we report a novel Senataxin mutation in a Cypriot ARCA family. Methods We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA families for linkage to known ARCA gene loci. We linked one family (909 to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing. Results Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients. Conclusion We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.

  12. Genetic Linkage Analysis of DFNB2 Locus with Autosomal Recessive Hearing Loss in Families Negative for GJB2 Mutations in Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Parisa Tahmasebi

    2016-09-01

    Full Text Available Abstract Background: Hearing loss is a common sensory impairment in humans which half of its causes are genetic reasons. Genetic hearing loss can be divided into the two types of syndromic and non-syndromic, which 80% of non-syndromic cases is Autosomal Recessive Non-Syndromic Hearing Loss. The aim of the present research is to determine the contribution of DFNB2 locus (MYO7A gene in causing an autosomal recessive hearing loss in the one group of the deaf families of Khuzestan province. Materials and Methods: This study was conducted on 26 families with autosomal recessive hearing loss (with 4 patients and negative for GJB2 mutations in Khuzestan province. 22 families suffered from ARNSHL and 4 families suffered from Usher syndrome. Linkage analysis was performed by using STR (Short Tandem Repeat markers related to DFNB2 locus. Each family’s genotype was determined by PCR-PAGE method. Furthermore, haplotypes drawing and LOD score calculations were performed. Results: From 26 families with hearing loss participating in this research, following genetic linkage analysis and haplotypes drawing, two families (7.7% of the families showed linkage to DFNB2 locus. One family (4.5% suffered from ARNSHL and another family suffered from Usher syndrome. Conclusion: The results of the present research show that the contribution of DFNB2 locus in causing hearing loss in the population of Khuzestan province was similar to other studies conducted in Iran and this locus with other important loci should be considered to check in the hearing loss panel.

  13. KohlschutterTonz Syndrome: Mutations in ROGDI and Evidence of Genetic Heterogeneity

    NARCIS (Netherlands)

    Tucci, A.; Kara, E.; Schossig, A.; Wolf, N.I.; Plagnol, V.; Fawcett, K.; Paisan-Ruiz, C.; Moore, M.; Hernandez, D.; Musumeci, S.; Tennison, M.; Hennekam, R.; Palmeri, S.; Malandrini, A.; Raskin, S.; Donnai, D.; Hennig, C.; Tzschach, A.; Hordijk, R.; Bast, T.; Wimmer, K.; Lo, C.N.; Shorvon, S.; Mefford, H.; Eichler, E.E.; Hall, R.; Hayes, I.; Hardy, J.; Singleton, A.; Zschocke, J.; Houlden, H.

    2013-01-01

    Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschütter in 1974, and to date,

  14. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation

    DEFF Research Database (Denmark)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian Gryesten

    2011-01-01

    BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study...

  15. Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene.

    Science.gov (United States)

    Stone, Edwin M; Luo, Xunda; Héon, Elise; Lam, Byron L; Weleber, Richard G; Halder, Jennifer A; Affatigato, Louisa M; Goldberg, Jacqueline B; Sumaroka, Alexander; Schwartz, Sharon B; Cideciyan, Artur V; Jacobson, Samuel G

    2011-12-28

    To determine the disease expression in autosomal recessive (ar) retinitis pigmentosa (RP) caused by mutations in the MAK (male germ cell-associated kinase) gene. Patients with RP and MAK gene mutations (n = 24; age, 32-77 years at first visit) were studied by ocular examination, perimetry, and optical coherence tomography (OCT). All but one MAK patient were homozygous for an identical truncating mutation in exon 9 and had Ashkenazi Jewish heritage. The carrier frequency of this mutation among 1207 unrelated Ashkenazi control subjects was 1 in 55, making it the most common cause of heritable retinal disease in this population and MAK-associated RP the sixth most common Mendelian disease overall in this group. Visual acuities could be normal into the eighth decade of life. Kinetic fields showed early loss in the superior-temporal quadrant. With more advanced disease, superior and midperipheral function was lost, but the nasal field remained. Only a central island was present at late stages. Pigmentary retinopathy was less prominent in the superior nasal quadrant. Rod-mediated vision was abnormal but detectable in the residual field; all patients had rod>cone dysfunction. Photoreceptor layer thickness was normal centrally but decreased with eccentricity. At the stages studied, there was no evidence of photoreceptor ciliary elongation. The patterns of disease expression in the MAK form of arRP showed some resemblance to patterns described in autosomal dominant RP, especially the form caused by RP1 mutations. The similarity in phenotypes is of interest, considering that there is experimental evidence of interaction between Mak and RP1 in the photoreceptor cilium.

  16. Two Cases of Autosomal Recessive Congenital Ichthyosis due to CYP4F22 Mutations: Expanding the Genotype of Self-Healing Collodion Baby

    NARCIS (Netherlands)

    Noguera-Morel, L.; Feito-Rodriguez, M.; Maldonado-Cid, P.; Garcia-Minaur, S.; Kamsteeg, E.J.; Gonzalez-Sarmiento, R.; Lucas-Laguna, R. De; Hernandez-Martin, A.; Torrelo, A.

    2016-01-01

    Collodion babies are born with a tight, shiny cast that sheds in a few weeks. After shedding, most patients will display features of autosomal recessive congenital ichthyosis (ARCI) later in life but in up to 10% of cases, the skin eventually becomes normal or only minimally involved, a phenotype

  17. Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses

    Directory of Open Access Journals (Sweden)

    Carsten Bergmann

    2018-02-01

    Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is a hepatorenal fibrocystic disorder that is characterized by enlarged kidneys with progressive loss of renal function and biliary duct dilatation and congenital hepatic fibrosis that leads to portal hypertension in some patients. Mutations in the PKHD1 gene are the primary cause of ARPKD; however, the disease is genetically not as homogeneous as long thought and mutations in several other cystogenes can phenocopy ARPKD. The family history usually is negative, both for recessive, but also often for dominant disease genes due to de novo arisen mutations or recessive inheritance of variants in genes that usually follow dominant patterns such as the main ADPKD genes PKD1 and PKD2. Considerable progress has been made in the understanding of polycystic kidney disease (PKD. A reduced dosage of disease proteins leads to the disruption of signaling pathways underlying key mechanisms involved in cellular homeostasis, which may help to explain the accelerated and severe clinical progression of disease course in some PKD patients. A comprehensive knowledge of disease-causing genes is essential for counseling and to avoid genetic misdiagnosis, which is particularly important in the prenatal setting (e.g., preimplantation genetic diagnosis/PGD. For ARPKD, there is a strong demand for early and reliable prenatal diagnosis, which is only feasible by molecular genetic analysis. A clear genetic diagnosis is helpful for many families and improves the clinical management of patients. Unnecessary and invasive measures can be avoided and renal and extrarenal comorbidities early be detected in the clinical course. The increasing number of genes that have to be considered benefit from the advances of next-generation sequencing (NGS which allows simultaneous analysis of a large group of genes in a single test at relatively low cost and has become the mainstay for genetic diagnosis. The broad phenotypic and genetic

  18. Novel compound heterozygous mutations in SERPINH1 cause rare autosomal recessive osteogenesis imperfecta type X.

    Science.gov (United States)

    Song, Y; Zhao, D; Xu, X; Lv, F; Li, L; Jiang, Y; Wang, O; Xia, W; Xing, X; Li, M

    2018-03-09

    We identified novel compound heterozygous mutations in SERPINH1 in a Chinese boy suffering from recurrent fractures, femoral deformities, and growth retardation, which resulted in extremely rare autosomal recessive OI type X. Long-term treatment of BPs was effective in increasing BMD Z-score, reducing fracture incidence and reshaping vertebrae compression. Osteogenesis imperfecta (OI) is a heritable bone disorder characterized by low bone mineral density, recurrent fractures, and progressive bone deformities. Mutation in serpin peptidase inhibitor clade H, member 1 (SERPINH1), which encodes heat shock protein 47 (HSP47), leads to rare autosomal recessive OI type X. We aimed to detect the phenotype and the pathogenic mutation of OI type X in a boy from a non-consanguineous Chinese family. We investigated the pathogenic mutations and analyzed their relationship with the phenotype in the patient using next-generation sequencing (NGS) and Sanger sequencing. Moreover, the efficacy of long-term bisphosphonate treatment in this patient was evaluated. The patient suffered from multiple fractures, low bone mass, and bone deformities in the femur, without dentinogenesis imperfecta or hearing loss. Compound heterozygous variants were found in SERPINH1 as follows: c.149 T>G in exon 2 and c.1214G>A in exon 5. His parents were heterozygous carriers of each of these mutations, respectively. Bisphosphonates could be helpful in increasing BMD Z-score, reducing bone fracture risk and reshaping the compressed vertebral bodies of this patient. We reported novel compound heterozygous mutations in SERPINH1 in a Chinese OI patient for the first time, which expanded the spectrum of phenotype and genotype of extremely rare OI type X.

  19. Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan

    Science.gov (United States)

    Ansar, Muhammad; Ramzan, Mohammad; Pham, Thanh L.; Yan, Kai; Jamal, Syed Muhammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

    2010-01-01

    For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod score 3.6). The genetic region for DFNB38 spans 10.1 cM according to the Marshfield genetic map and is bounded by markers D6S980 and D6S1719. This genetic region corresponds to 3.4 MB on the sequence-based physical map. PMID:12890929

  20. Mutations in the ABCA4 (ABCR) Gene Are the Major Cause of Autosomal Recessive Cone-Rod Dystrophy

    OpenAIRE

    Maugeri, Alessandra; Klevering, B. Jeroen; Rohrschneider, Klaus; Blankenagel, Anita; Brunner, Han G.; Deutman, August F.; Hoyng, Carel B.; Cremers, Frans P. M.

    2000-01-01

    The photoreceptor cell–specific ATP-binding cassette transporter gene (ABCA4; previously denoted “ABCR”) is mutated in most patients with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients with isolated CRD, all fro...

  1. Molecular genetic analysis of consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia.

    Science.gov (United States)

    Bibi, Nosheen; Ahmad, Saeed; Ahmad, Wasim; Naeem, Muhammad

    2011-02-01

    Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

  2. New autosomal recessive faciodigitogenital syndrome.

    OpenAIRE

    Teebi, A S; Naguib, K K; Al-Awadi, S; Al-Saleh, Q A

    1988-01-01

    Most pedigrees of Aarskog's faciodigitogenital syndrome have suggested X linked inheritance. However, sex influenced autosomal dominant inheritance is also a possibility in some families. We describe an Arab family of normal consanguineous parents with five children (three males and two females) with some features of Aarskog syndrome in addition to some unusual hair changes. The possibility that this family represents a distinct previously unrecognised faciodigitogenital syndrome with short s...

  3. An autosomal recessive leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa maps to chromosome 17q24.2-25.3

    OpenAIRE

    Bouhouche Ahmed; Benomar Ali; Errguig Leila; Lachhab Lamiae; Bouslam Naima; Aasfara Jehanne; Sefiani Sanaa; Chabraoui Layachi; El Fahime Elmostafa; El Quessar Abdeljalil; Jiddane Mohamed; Yahyaoui Mohamed

    2012-01-01

    Abstract Background Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. To identify new genes responsible of such diseases, we studied a consanguineous Moroccan family with three affected individuals displaying hereditary leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa that appears to segregate in autosomal recessive pattern. Methods All family members underwent neurologic...

  4. Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

    Science.gov (United States)

    Klevering, B Jeroen; Yzer, Suzanne; Rohrschneider, Klaus; Zonneveld, Marijke; Allikmets, Rando; van den Born, L Ingeborgh; Maugeri, Alessandra; Hoyng, Carel B; Cremers, Frans P M

    2004-12-01

    Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or autosomal recessive CRD (54 cases) or RP (90 cases). We performed detailed ophthalmologic examinations and identified at least one ABCA4 mutation in 18 patients (33%) with CRD and in five patients (5.6%) with RP. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing revealed four novel missense mutations (R24C, E161K, P597S, G618E) and a novel 1-bp deletion (5888delG). Ophthalmoscopic abnormalities in CRD patients ranged from minor granular pigmentary changes in the posterior pole to widespread atrophy. In 12 patients with recordable electroretinogram (ERG) tracings, a cone-rod pattern was detected. Three patients demonstrated progression from a retinal dystrophy resembling STGD1 to a more widespread degeneration, and were subsequently diagnosed as CRD. In addition to a variable degree of atrophy, all RP patients displayed ophthalmologic characteristics of classic RP. When detectable, ERG recordings in these patients demonstrated rod-cone patterns of photoreceptor degeneration. In conclusion, in this study, we show that the ABCA4 mutation chip is an efficient first screening tool for arCRD.

  5. Autosomal recessive Oliver-McFarlane syndrome: retinitis pigmentosa, short stature (GH deficiency), trichomegaly, and hair anomalies or CPD syndrome (chorioretinopathy-pituitary dysfunction).

    Science.gov (United States)

    Haimi, Motti; Gershoni-Baruch, Ruth

    2005-10-15

    We describe a brother and sister with retinitis pigmentosa (RP), growth failure, long eyelashes, and sparse hair. They were born to young healthy consanguineous parents and presented at birth with IUGR. Evolving pigmentary retinopathy was diagnosed at the age of 5 years. A similar condition (Oliver-McFarlane) syndrome was reported previously. Our two sibs confirm the existence of this autosomal recessive syndrome.

  6. Otologic Manifestations of Autosomal Recessive Congenital Ichthyosis in Children.

    Science.gov (United States)

    Martín-Santiago, A; Rodríguez-Pascual, M; Knöpfel, N; Hernández-Martín, Á

    2015-11-01

    Few studies have investigated ear involvement in nonsyndromic autosomal recessive congenital ichthyosis (ARCI). To assess the type and frequency of otologic manifestations of ARCI in patients under follow-up at the pediatric dermatology department of our hospital. We prospectively studied the presence of ear pain, ear itching, tinnitus, otitis, cerumen impaction, accumulation of epithelial debris, and hearing loss. Daily hygiene measures, topical treatments, medical-surgical interventions, and frequency of visits to an ear, nose, and throat (ENT) specialist were noted in the patients' medical records. Ear examination and hearing tests were performed in all cases. Ten patients were studied: 2 had a self-healing collodion baby phenotype and 8 had ichthyosis. There was mention of otologic manifestations in the records of all 8 patients with ichthyosis (100%); 6 of these patients (75%) had abnormalities in the external auditory canal examination and 2 (25%) had conductive hearing loss. Our findings are limited by the small number of patients studied, all of whom were younger than 19 years. The involvement of both dermatologists and ENT specialists in the management of patients with ichthyosis is crucial to ensure the application of the best therapeutic and preventive measures. More studies are needed to assess the prevalence and impact on quality of life of ear involvement in patients with ichthyosis and to determine the optimal interval between ENT visits for these patients. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  7. Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID

    Directory of Open Access Journals (Sweden)

    Saleha Shamim

    2017-05-01

    Full Text Available Intellectual disability (ID is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID or non-syndromic (NS-ID. ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

  8. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: vmss@nuclear.inin.mx

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the

  9. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V M; Pimentel, P A.E.; Cruces, M P [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin on

  10. An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy.

    Science.gov (United States)

    Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido; Ben-Yosef, Tamar

    2015-01-01

    To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. Patients underwent a detailed ophthalmic evaluation, including eye examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potential (VEP). Genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing. The affected family members are three siblings who have various degrees of progressive visual deterioration, glare, color vision abnormalities, and night vision difficulties. Visual field tests revealed central scotomas of different extension. Cone and rod ERG responses were reduced, with cones more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice sites. However, in intron 21, proximate to the intron-exon junction, we observed a homozygous 10 bp deletion between positions -26 and -17 (c.2281-26_-17del). The deletion was linked to a known SNP, c.2281-6C>G. The deletion cosegregated with the disease in the family, and was not detected in public databases or in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence. The in vitro splicing assay demonstrated that c.2281-26_-17del leads to complete exon 22 skipping. A novel

  11. Autosomal recessive retinitis pigmentosa with RP1 mutations is associated with myopia.

    Science.gov (United States)

    Chassine, Thomas; Bocquet, Béatrice; Daien, Vincent; Avila-Fernandez, Almudena; Ayuso, Carmen; Collin, Rob Wj; Corton, Marta; Hejtmancik, J Fielding; van den Born, L Ingeborgh; Klevering, B Jeroen; Riazuddin, S Amer; Sendon, Nathacha; Lacroux, Annie; Meunier, Isabelle; Hamel, Christian P

    2015-10-01

    To determine the refractive error in patients with autosomal recessive retinitis pigmentosa (arRP) caused by RP1 mutations and to compare it with that of other genetic subtypes of RP. Twenty-six individuals had arRP with RP1 mutations, 25 had autosomal dominant RP (adRP) with RP1 mutation, 8 and 33 had X-linked RP (xlRP) with RP2 and RPGR mutations, respectively, 198 and 93 had Usher syndrome and arRP without RP1 mutations, respectively. The median of the spherical equivalent (SE) and the IQR (Q25-Q75) was determined and multiple comparisons were performed. arRP patients with RP1 mutations had SE median at -4.0 dioptres (D) OD (Ocula Dextra); -3.88 D OS (Ocula Sinistra), whereas arRP patients without RP1 mutations (-0.50 D OD; -0.75 D OS) and Usher syndrome patients (-0.50 D OD; -0.38 D OS) were significantly less myopic (pUsher syndrome and adRP with RP1 mutation had a narrow IQR (-9.06 to -1.13 D), whereas arRP with RP1 mutations and xlRP with RP2 or RPGR mutations had a larger range (-9.06; -1.13 D). arRP patients with RP1 mutations have myopia not different from patients with xlRP with RP2 or RPGR mutations, while RP patients from other genetic subgroups were emmetropic or mildly myopic. We suggest that arRP patients with high myopic refractive error should be preferentially analysed for RP1 mutations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis.

    Science.gov (United States)

    Bordbar, Mohammad Reza; Modarresi, Farzaneh; Farazi Fard, Mohammad Ali; Dastsooz, Hassan; Shakib Azad, Nader; Faghihi, Mohammad Ali

    2017-05-03

    Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis. Therefore, genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2). Here, we report a novel missense mutation in an 8-year-old boy suffered from hepatosplenomegaly, hepatitis, epilepsy and pancytopenia. The patient was born to a first-cousin parents with no previous documented disease in his parents. To identify mutated gene in the proband, Whole Exome Sequencing (WES) utilizing next generation sequencing was used on an Illumina HiSeq 2000 platform on DNA sample from the patient. Results showed a novel deleterious homozygous missense mutation in PRF1 gene (NM_001083116: exon3: c. 1120 T > G, p.W374G) in the patient and then using Sanger sequencing it was confirmed in the proband and his parents. Since his parents were heterozygous for the identified mutation, autosomal recessive pattern of inheritance was confirmed in the family. Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease.

  13. Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy

    International Nuclear Information System (INIS)

    Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie.

    1987-01-01

    Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings · adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT. (author)

  14. A Rare Variant in PGAP2 Causes Autosomal Recessive Hyperphosphatasia with Mental Retardation Syndrome, with a Mild Phenotype in Heterozygous Carriers

    Directory of Open Access Journals (Sweden)

    Yonatan Perez

    2017-01-01

    Full Text Available Mutations in genes involved in the biosynthesis of the glycosylphosphatidylinositol (GPI anchor cause autosomal recessive glycosylation defects, with a wide phenotypic spectrum of intellectual disability, seizures, minor facial dysmorphism, hypotonia, and elevated serum alkaline phosphatase. We now describe consanguineous Bedouin kindred presenting with an autosomal recessive syndrome of intellectual disability and elevated serum alkaline phosphatase. Genome-wide linkage analysis identified 6 possible disease-associated loci. Whole-exome sequencing followed by Sanger sequencing validation identified a single variant in PGAP2 as the disease-causing mutation (C.554G>A; p.185(R>Q, segregating as expected within the kindred and not found in 150 Bedouin controls. The mutation replaces a highly conserved arginine residue with glutamine within the Frag1 (FGF receptor activating domain of PGAP2. Interestingly, this mutation is a known dbSNP variant (rs745521288, build 147 with a very low allele frequency (0.00000824 in dbSNP, no homozygotes reported, highlighting the fact that dbSNP variants should not be automatically ruled out as disease-causing mutations. We further showed that PGAP2 is ubiquitously expressed, but in line with the disease phenotype, it is highly transcribed in human brain, skeletal muscle, and liver. Interestingly, a mild phenotype of slightly elevated serum levels of alkaline phosphatase and significant learning disabilities was observed in heterozygous carriers.

  15. Identification of a Novel Dentin Matrix Protein-1 (DMP-1) Mutation and Dental Anomalies in a Kindred with Autosomal Recessive Hypophosphatemia

    OpenAIRE

    Turan, Serap; Aydin, Cumhur; Bereket, Abdullah; Akcay, Teoman; Güran, Tülay; Yaralioglu, Betul Akmen; Bastepe, Murat; Jüppner, Harald

    2009-01-01

    An autosomal recessive form of hypophosphatemia (ARHP) was recently shown to be caused by homozygous mutations in DMP1, the gene encoding dentin matrix protein-1 (DMP-1), a non-collagenous bone matrix protein with an important role in the development and mineralization of bone and teeth. Here, we report a previously not reported consanguineous ARHP kindred in which the three affected individuals carry a novel homozygous DMP-1 mutation. The index case presented at the age of 3 years with bowin...

  16. Unusual extrinsic staining following microabrasion in a girl with amelogenesis imperfecta.

    Science.gov (United States)

    Rogers, H J; Yesudian, G; Rodd, H D

    2016-08-01

    Developmental defects of enamel (DDE), such as amelogenesis imperfecta (AI), may present with tooth discolouration that is of aesthetic concern to the affected individual. Children and young people with DDE may therefore seek dental interventions to improve their dental appearance. The most commonly employed approaches include microabrasion, bleaching and/or placement of composite resin veneers. A 13-year-old girl with hypomature AI requested treatment for the 'marks' on her teeth which were having a negative impact on her social interactions. Clinical examination revealed generalised dense white opacities, and a microabrasion approach was performed on 11, 12 and 13 using a commercial preparation of 6.6 % hydrochloric acid. Concerningly, the girl's father phoned the next day reporting that his daughter's teeth had turned 'orange'. An urgent review revealed that the treated teeth had indeed become an orange colour. Further enquiry found that the patient had eaten a tomato pizza immediately after her dental treatment and this was believed to have caused the severe extrinsic staining. The patient was provided with a 16 % carbamide peroxide preparation for night-time use in a laboratory-made tray. A 2-week review revealed complete resolution of the staining. Direct composite resin restorations were subsequently provided for the girl's maxillary anterior teeth to achieve an optimal cosmetic result and she has remained pleased with her dental appearance. Clinicians should be aware of the potential for extrinsic staining following microabrasion or tooth bleaching. Patients should be advised against consuming coloured food and drink for at least 48 h after their treatment.

  17. Identification of FASTKD2 compound heterozygous mutations as the underlying cause of autosomal recessive MELAS-like syndrome.

    Science.gov (United States)

    Yoo, Da Hye; Choi, Young-Chul; Nam, Da Eun; Choi, Sun Seong; Kim, Ji Won; Choi, Byung-Ok; Chung, Ki Wha

    2017-07-01

    Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many parts of the body, particularly the brain and muscles. This study examined a Korean MELAS-like syndrome patient with seizure, stroke-like episode, and optic atrophy. Target sequencing of whole mtDNA and 73 nuclear genes identified compound heterozygous mutations p.R205X and p.L255P in the FASTKD2. Each of his unaffected parents has one of the two mutations, and both mutations were not found in 302 controls. FASTKD2 encodes a FAS-activated serine-threonine (FAST) kinase domain 2 which locates in the mitochondrial inner compartment. A FASTKD2 nonsense mutation was once reported as the cause of a recessive infantile mitochondrial encephalomyopathy. The present case showed relatively mild symptoms with a late onset age, compared to a previous patient with FASTKD2 mutation, implicating an inter-allelic clinical heterogeneity. Because this study is the second report of an autosomal recessive mitochondrial encephalomyopathy patient with a FASTKD2 mutation, it will extend the phenotypic spectrum of the FASTKD2 mutation. Copyright © 2017. Published by Elsevier B.V.

  18. Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa.

    Science.gov (United States)

    Arno, Gavin; Agrawal, Smriti A; Eblimit, Aiden; Bellingham, James; Xu, Mingchu; Wang, Feng; Chakarova, Christina; Parfitt, David A; Lane, Amelia; Burgoyne, Thomas; Hull, Sarah; Carss, Keren J; Fiorentino, Alessia; Hayes, Matthew J; Munro, Peter M; Nicols, Ralph; Pontikos, Nikolas; Holder, Graham E; Asomugha, Chinwe; Raymond, F Lucy; Moore, Anthony T; Plagnol, Vincent; Michaelides, Michel; Hardcastle, Alison J; Li, Yumei; Cukras, Catherine; Webster, Andrew R; Cheetham, Michael E; Chen, Rui

    2016-12-01

    Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability

    DEFF Research Database (Denmark)

    Hansen, Lars; Tawamie, Hasan; Murakami, Yoshiko

    2013-01-01

    PGAP2 encodes a protein involved in remodeling the glycosylphosphatidylinositol (GPI) anchor in the Golgi apparatus. After synthesis in the endoplasmic reticulum (ER), GPI anchors are transferred to the proteins and are remodeled while transported through the Golgi to the cell membrane. Germline...... mutations in six genes (PIGA, PIGL, PIGM, PIGV, PIGN, and PIGO) in the ER-located part of the GPI-anchor-biosynthesis pathway have been reported, and all are associated with phenotypes extending from malformation and lethality to severe intellectual disability, epilepsy, minor dysmorphisms, and elevated...... alkaline phosphatase (ALP). We performed autozygosity mapping and ultra-deep sequencing followed by stringent filtering and identified two homozygous PGAP2 alterations, p.Tyr99Cys and p.Arg177Pro, in seven offspring with nonspecific autosomal-recessive intellectual disability from two consanguineous...

  20. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A

    1998-01-01

    -5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present...... molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia. Udgivelsesdato: 1998-May-15...

  1. Multiple Unerupted Teeth with Amelogenesis Imperfecta in Siblings

    OpenAIRE

    Shruthi Hegde

    2012-01-01

    Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple mo...

  2. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    Science.gov (United States)

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Characterization of the nanoscratch, microstructure, and composition in hypoplastic amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Ping Qing

    2015-07-01

    Full Text Available Hypoplastic amelogenesis imperfecta is a widespread hereditary disease that causes the loss of enamel. The purpose of this study was to investigate the nanoscratch resistance of hypoplastic amelogenesis imperfecta for providing a reference for restorative treatment. Four unerupted third molars from a patient diagnosed with hypoplastic amelogenesis imperfecta and seven unerupted third molars from normal individuals were compared. Atomic force microscopy and energy-dispersive X-ray spectroscopy were used to observe the microstructure and composition of the teeth (enamel and dentin. The nanoscratch tests of teeth (enamel and dentin were investigated using a nanoscratch tester, scanning electron microscopy, and a stylus profilometer. The results indicated that hypoplastic amelogenesis imperfecta teeth had different microstructures compared to normal teeth. Hypoplastic amelogenesis imperfecta demonstrated a higher composition of organic substance. Meanwhile, the friction coefficient of hypoplastic amelogenesis imperfecta was higher than that of normal teeth, and inferior frictional resistance of hypoplastic amelogenesis imperfecta teeth was observed. The main damaging mechanisms observed in hypoplastic amelogenesis imperfecta under nanoscratch were the combination of delamination, debris, and cracks in enamel with delamination, debris, and plastic deformation in dentin. Our findings suggested that new dental restorative materials should be selected to match the mechanical properties of hypoplastic amelogenesis imperfecta.

  4. Integration-free induced pluripotent stem cells derived from a patient with autosomal recessive Alport syndrome (ARAS).

    Science.gov (United States)

    Kuebler, Bernd; Aran, Begoña; Miquel-Serra, Laia; Muñoz, Yolanda; Ars, Elisabet; Bullich, Gemma; Furlano, Monica; Torra, Roser; Marti, Merce; Veiga, Anna; Raya, Angel

    2017-12-01

    A skin biopsy was obtained from a 25-year-old female patient with autosomal recessive Alport syndrome (ARAS) with the homozygous COL4A3 mutation c.345delG, p.(P166Lfs*37). Dermal fibroblasts were derived and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53shRNA. The generated induced Pluripotent Stem Cell (iPSC) clone AS FiPS1 Ep6F-2 was free of genomically integrated reprogramming genes, had the specific homozygous mutation, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. This iPSC line offers a useful resource to study Alport syndrome pathomechanisms and drug testing. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  5. Nephrocalcinosis in Amelogenesis Imperfecta Caused by the FAM20A Mutation.

    Science.gov (United States)

    Koruyucu, Mine; Seymen, Figen; Gencay, Genco; Gencay, Koray; Tuna, Elif Bahar; Shin, Teo Jeon; Hyun, Hong-Keun; Kim, Young-Jae; Kim, Jung-Wook

    2018-01-01

    Enamel-renal syndrome is characterized by nephrocalcinosis, enamel defects, gingival hyperplasia and eruption failures. It has been recently identified that recessive mutations in the FAM20A gene result in amelogenesis imperfecta (AI)-gingival fibromatosis. The aim of this research to determine whether AI patients with known -FAM20A mutations also have nephrocalcinosis. Complete oral and radiological examinations were performed for all participating family members. Renal examinations were performed using ultrasound. The teeth were evaluated for severe loss, and multiple eruption failures were evident from the clinical and radiological examinations. Unexpected extensive and fast crown resorption was found by radiological examination. Renal ultrasound revealed bilateral nephrocalcinosis in both affected individuals. Recessive FAM20A mutations can cause nephrocalcinosis in addition to the oral phenotype. AI patients with similar clinical phenotypes and FAM20A mutations should be examined for nephropathy even if they lack pertinent symptoms. Nephrology referral is warranted for patients who have clinical phenotypes related to AI-gingival fibromatosis even if they are not symptomatic. © 2018 S. Karger AG, Basel.

  6. AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE AND CONGENITAL HEPATIC FIBROSIS: SUMMARY STATEMENT OF A FIRST NATIONAL INSTITUTES OF HEALTH/OFFICE OF RARE DISEASES CONFERENCE

    Science.gov (United States)

    Gunay-Aygun, Meral; Avner, Ellis D.; Bacallo, Robert L.; Choyke, Peter L.; Flynn, Joseph T.; Germino, Gregory G.; Guay-Woodford, Lisa; Harris, Peter; Heller, Theo; Ingelfinger, Julie; Kaskel, Frederick; Kleta, Robert; LaRusso, Nicholas F.; Mohan, Parvathi; Pazour, Gregory J.; Shneider, Benjamin L.; Torres, Vicente E.; Wilson, Patricia; Zak, Colleen; Zhou, Jing; Gahl, William A.

    2010-01-01

    Researchers and clinicians with expertise in autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF) and related fields met on May 5-6, 2005, on the National Institutes of Health (NIH) campus for a 1.5-day symposium sponsored by the NIH Office of Rare Diseases, the National Human Genome Research Institute (NHGRI), and in part by the ARPKD/CHF Alliance. The meeting addressed the present status and the future of ARPKD/CHF research. PMID:16887426

  7. Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

    Science.gov (United States)

    Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

    2018-01-01

    The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  8. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia

    DEFF Research Database (Denmark)

    Grau, Tanja; Artemyev, Nikolai O; Rosenberg, Thomas

    2011-01-01

    study on PDE6C mutations including the mutation spectrum, its prevalence in a large cohort of ACHM/cone dysfunction patients, the clinical phenotype and the functional characterization of mutant PDE6C proteins. Twelve affected patients from seven independent families segregating PDE6C mutations were......Mutations in the gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase (PDE6C) have been recently reported in patients with autosomal recessive inherited achromatopsia (ACHM) and early-onset cone photoreceptor dysfunction. Here we present the results of a comprehensive...... identified in our total patient cohort of 492 independent families. Eleven different PDE6C mutations were found including two nonsense mutations, three mutations affecting transcript splicing as shown by minigene assays, one 1 bp-insertion and five missense mutations. We also performed a detailed functional...

  9. Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

    Directory of Open Access Journals (Sweden)

    Cornel Martina C

    2010-07-01

    Full Text Available Abstract Background The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. Methods/Design This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. Discussion This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous

  10. Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations

    Science.gov (United States)

    Marzouka, Nour al Dain; Hebrard, Maxime; Manes, Gaël; Sénéchal, Audrey; Meunier, Isabelle; Hamel, Christian P.

    2013-01-01

    Purpose Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP. Methods arRP patients underwent standard ophthalmic examination, Goldman perimetry, fundus examination, retinal OCT, autofluorescence measurement, and full-field electroretinogram. Fifteen consanguineous families with arRP excluded for USH2A and EYS were genotyped on 250 K SNP arrays. Homozygous regions were listed, and known genes within these regions were PCR sequenced. Familial segregation and mutation analyzes were performed. Results We found ten mutations, seven of which were novel mutations in eight known genes, including RP1, IMPG2, NR2E3, PDE6A, PDE6B, RLBP1, CNGB1, and C2ORF71, in ten out of 15 families. The patients carrying RP1, C2ORF71, and IMPG2 mutations presented with severe RP, while those with PDE6A, PDE6B, and CNGB1 mutations were less severely affected. The five families without mutations in known genes could be a source of identification of novel genes. Conclusions Homozygosity mapping combined with systematic screening of known genes results in a positive molecular diagnosis in 66.7% of families. PMID:24339724

  11. Amelogenesis imperfecta: review of diagnostic findings and treatment concepts.

    Science.gov (United States)

    Sabandal, Martin M I; Schäfer, Edgar

    2016-09-01

    Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option.

  12. Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

    Science.gov (United States)

    Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

    2014-12-01

    Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. © 2014 Wiley Periodicals, Inc.

  13. A Novel Homozygous Missense Mutation in HOXC13 Leads to Autosomal Recessive Pure Hair and Nail Ectodermal Dysplasia.

    Science.gov (United States)

    Li, Xiaoxiao; Orseth, Meredith Lee; Smith, J Michael; Brehm, Mary Abigail; Agim, Nnenna Gebechi; Glass, Donald Alexander

    2017-03-01

    Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development. © 2017 Wiley Periodicals, Inc.

  14. The population genetics of X-autosome synthetic lethals and steriles.

    Science.gov (United States)

    Lachance, Joseph; Johnson, Norman A; True, John R

    2011-11-01

    Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

  15. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report.

    Science.gov (United States)

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem

    2015-09-01

    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  16. Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts.

    Science.gov (United States)

    Irum, Bushra; Khan, Shahid Y; Ali, Muhammad; Daud, Muhammad; Kabir, Firoz; Rauf, Bushra; Fatima, Fareeha; Iqbal, Hira; Khan, Arif O; Al Obaisi, Saif; Naeem, Muhammad Asif; Nasir, Idrees A; Khan, Shaheen N; Husnain, Tayyab; Riazuddin, Sheikh; Akram, Javed; Eghrari, Allen O; Riazuddin, S Amer

    2016-01-01

    The aim of this study is to identify the molecular basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous pedigree. All participating individuals underwent a detailed ophthalmic examination. Each patient's medical history, particularly of cataracts and other ocular abnormalities, was compiled from available medical records and interviews with family elders. Blood samples were donated by all participating family members and used to extract genomic DNA. Genetic analysis was performed to rule out linkage to known arCC loci and genes. Whole-exome sequencing libraries were prepared and paired-end sequenced. A large deletion was found that segregated with arCC in the family, and chromosome walking was conducted to estimate the proximal and distal boundaries of the deletion mutation. Exclusion and linkage analysis suggested linkage to a region of chromosome 6p24 harboring GCNT2 (glucosaminyl (N-acetyl) transferase 2) with a two-point logarithm of odds score of 5.78. PCR amplifications of the coding exons of GCNT2 failed in individuals with arCC, and whole-exome data analysis revealed a large deletion on chromosome 6p in the region harboring GCNT2. Chromosomal walking using multiple primer pairs delineated the extent of the deletion to approximately 190 kb. Interestingly, a failure to amplify a junctional fragment of the deletion break strongly suggests an insertion in addition to the large deletion. Here, we report a novel insertion/deletion mutation at the GCNT2 locus that is responsible for congenital cataracts in a large consanguineous family.

  17. Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease

    DEFF Research Database (Denmark)

    Gal, Andreas; Rau, Isabella; El Matri, Leila

    2011-01-01

    Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we...... the affinity and reactivity of the enzyme toward in vivo protein substrates are likely to be substantially reduced....... heterogeneity of the trait. Using RT-PCR, PRSS56 transcripts were detected in samples derived from the human adult retina, cornea, sclera, and optic nerve. The expression of the mouse ortholog could be first detected in the eye at E17 and was maintained into adulthood. The predicted PRSS56 protein is a 603...

  18. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration.

    Science.gov (United States)

    Iqbal, Zafar; Püttmann, Lucia; Musante, Luciana; Razzaq, Attia; Zahoor, Muhammad Yasir; Hu, Hao; Wienker, Thomas F; Garshasbi, Masoud; Fattahi, Zohreh; Gilissen, Christian; Vissers, Lisenka E L M; de Brouwer, Arjan P M; Veltman, Joris A; Pfundt, Rolph; Najmabadi, Hossein; Ropers, Hans-Hilger; Riazuddin, Sheikh; Kahrizi, Kimia; van Bokhoven, Hans

    2016-03-01

    AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p.(Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far.

  19. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

    Science.gov (United States)

    Iqbal, Zafar; Püttmann, Lucia; Musante, Luciana; Razzaq, Attia; Zahoor, Muhammad Yasir; Hu, Hao; Wienker, Thomas F; Garshasbi, Masoud; Fattahi, Zohreh; Gilissen, Christian; Vissers, Lisenka ELM; de Brouwer, Arjan PM; Veltman, Joris A; Pfundt, Rolph; Najmabadi, Hossein; Ropers, Hans-Hilger; Riazuddin, Sheikh; Kahrizi, Kimia; van Bokhoven, Hans

    2016-01-01

    AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p.(Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far. PMID:26173967

  20. Genetic spectrum of autosomal recessive non-syndromic hearing loss in Pakistani families.

    Directory of Open Access Journals (Sweden)

    Sobia Shafique

    Full Text Available The frequency of inherited bilateral autosomal recessive non-syndromic hearing loss (ARNSHL in Pakistan is 1.6/1000 individuals. More than 50% of the families carry mutations in GJB2 while mutations in MYO15A account for about 5% of recessive deafness. In the present study a cohort of 30 ARNSHL families was initially screened for mutations in GJB2 and MYO15A. Homozygosity mapping was performed by employing whole genome single nucleotide polymorphism (SNP genotyping in the families that did not carry mutations in GJB2 or MYO15A. Mutation analysis was performed for the known ARNSHL genes present in the homozygous regions to determine the causative mutations. This allowed the identification of a causative mutation in all the 30 families including 9 novel mutations, which were identified in 9 different families (GJB2 (c.598G>A, p.Gly200Arg; MYO15A (c.9948G>A, p.Gln3316Gln; c.3866+1G>A; c.8767C>T, p.Arg2923* and c.8222T>C, p.Phe2741Ser, TMC1 (c.362+18A>G, BSND (c.97G>C, p.Val33Leu, TMPRSS3 (c.726C>G, p.Cys242Trp and MSRB3 (c.20T>G, p.Leu7Arg. Furthermore, 12 recurrent mutations were detected in 21 other families. The 21 identified mutations included 10 (48% missense changes, 4 (19% nonsense mutations, 3 (14% intronic mutations, 2 (9% splice site mutations and 2 (9% frameshift mutations. GJB2 accounted for 53% of the families, while mutations in MYO15A were the second most frequent (13% cause of ARNSHL in these 30 families. The identification of novel as well as recurrent mutations in the present study increases the spectrum of mutations in known deafness genes which could lead to the identification of novel founder mutations and population specific mutated deafness genes causative of ARNSHL. These results provide detailed genetic information that has potential diagnostic implication in the establishment of cost-efficient allele-specific analysis of frequently occurring variants in combination with other reported mutations in Pakistani populations.

  1. Additional case of Marden-Walker syndrome: support for the autosomal-recessive inheritance adn refinement of phenotype in a surviving patient.

    Science.gov (United States)

    Orrico, A; Galli, L; Zappella, M; Orsi, A; Hayek, G

    2001-02-01

    In this report, we present a 14-year-old girl, born to consanguineous parents, who presented with severe mental retardation, hypotonia, short stature, and congenital joint contractures. The craniofacial features were scaphocephaly, thin/long and immobile face, marked hypoplasia of the midface, temporal narrowness, blepharophimosis, palpebral ptosis, and strabismus. The combination of such a distinctive craniofacial appearance and psychomotor retardation allows us to recognize a new case of the Marden-Walker syndrome. Our patient represents one of the rare cases in which consanguineous mating supports the autosomal-recessive pattern of inheritance of this condition. Furthermore, through refining the phenotype of a surviving patient, this report may contribute to a better recognition of this disorder in older affected children.

  2. Amelogenesis imperfecta and the treatment plan - interdisciplinary team approach.

    Science.gov (United States)

    Suchancova, B; Holly, D; Janska, M; Stebel, J; Lysy, J; Thurzo, A; Sasinek, S

    2014-01-01

    Amelogenesis imperfecta is a set of hereditary defects representing mainly the development defects of enamel without the presence of whole-body symptoms. Developmental disorders can manifest a complete absence of enamel, which is caused by improper differentiation of ameloblasts. This article describes the diagnosis and treatment of a patient with amelogenesis imperfecta, as well as the need for interdisciplinary cooperation to achieve the best possible morphological, skeletal, functional and aesthetic rehabilitation of the patients with this diagnosis. Furthermore, the article reviews literature dealing with other anomalies occurring in association with amelogenesis imperfect (Fig. 12, Ref. 20).

  3. Characterization of the nanoscratch, microstructure, and composition in hypoplastic amelogenesis imperfecta

    OpenAIRE

    Ping Qing; Yue Li; Shanshan Gao; Mengting Qiao; Linmao Qian; Haiyang Yu

    2015-01-01

    Hypoplastic amelogenesis imperfecta is a widespread hereditary disease that causes the loss of enamel. The purpose of this study was to investigate the nanoscratch resistance of hypoplastic amelogenesis imperfecta for providing a reference for restorative treatment. Four unerupted third molars from a patient diagnosed with hypoplastic amelogenesis imperfecta and seven unerupted third molars from normal individuals were compared. Atomic force microscopy and energy-dispersive X-ray spectroscopy...

  4. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia

    DEFF Research Database (Denmark)

    Roos, L; Fang, M; Dali, C

    2013-01-01

    to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where...... three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented...... with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations....

  5. Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry

    NARCIS (Netherlands)

    Mekahli, Djalila; van Stralen, Karlijn J.; Bonthuis, Marjolein; Jager, Kitty J.; Balat, Ayşe; Benetti, Elisa; Godefroid, Nathalie; Edvardsson, Vidar O.; Heaf, James G.; Jankauskiene, Augustina; Kerecuk, Larissa; Marinova, Svetlana; Puteo, Flora; Seeman, Tomas; Zurowska, Aleksandra; Pirenne, Jacques; Schaefer, Franz; Groothoff, Jaap W.; Levtchenko, E.; Haffner, D.; Bjerre, A.; Massy, Z.; Shtiza, D.; Kramar, R.; Oberbauer, R.; Baiko, S.; Sukalo, A.; van Hoeck, K.; Collart, F.; des Grottes, J. M.; Pokrajac, D.; Roussinov, D.; Batinić , D.; Lemac, M.; Slavicek, J.; Seeman, T.; Vondrak, K.; Heaf, J. G.; Toots, U.; Finne, P.; Grö nhagen-Riska, C.; Couchoud, C.; Lasalle, M.; Sahpazova, E.; Abazi, N.; Ristoka Bojkovska, N.; von Gersdorff, G.; Scholz, C.; Tö nshoff, B.; Krupka, K.

    2016-01-01

    The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these

  6. Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry

    NARCIS (Netherlands)

    Mekahli, D.; Stralen, K.J. van; Bonthuis, M.; Jager, K.J.; Balat, A.; Benetti, E.; Godefroid, N.; Edvardsson, V.O.; Heaf, J.G.; Jankauskiene, A.; Kerecuk, L.; Marinova, S.; Puteo, F.; Seeman, T.; Zurowska, A.; Pirenne, J.; Schaefer, F.; Groothoff, J.W.; Hoitsma, A.J.; et al.,

    2016-01-01

    BACKGROUND: The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in

  7. Regulation of pH During Amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Nanci, Antonio; Kurtz, Ira; Wright, J Timothy; Paine, Michael L

    2010-02-01

    During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation.

  8. A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability.

    Science.gov (United States)

    Larti, Farzaneh; Kahrizi, Kimia; Musante, Luciana; Hu, Hao; Papari, Elahe; Fattahi, Zohreh; Bazazzadegan, Niloofar; Liu, Zhe; Banan, Mehdi; Garshasbi, Masoud; Wienker, Thomas F; Ropers, H Hilger; Galjart, Niels; Najmabadi, Hossein

    2015-03-01

    In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score = 3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID.

  9. DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome

    DEFF Research Database (Denmark)

    White, Janson; Mazzeu, Juliana F; Hoischen, Alexander

    2015-01-01

    Robinow syndrome is a genetically heterogeneous disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features and for which both autosomal-recessive and autosomal-dominant inheritance patterns have been described. Causative variants in the non-canonical ...

  10. X-Linked and Autosomal Recessive Alport Syndrome

    DEFF Research Database (Denmark)

    Savige, Judith; Storey, Helen; Il Cheong, Hae

    2016-01-01

    Alport syndrome results from mutations in the COL4A5 (X-linked) or COL4A3/COL4A4 (recessive) genes. This study examined 754 previously- unpublished variants in these genes from individuals referred for genetic testing in 12 accredited diagnostic laboratories worldwide, in addition to all published...... COL4A5, COL4A3 and COL4A4 variants in the LOVD databases. It also determined genotype-phenotype correlations for variants where clinical data were available. Individuals were referred for genetic testing where Alport syndrome was suspected clinically or on biopsy (renal failure, hearing loss...

  11. The acrocallosal syndrome in first cousins: widening of the spectrum of clinical features and further support for autosomal recessive inheritance.

    Science.gov (United States)

    Schinzel, A

    1988-01-01

    First cousins, related through their mothers, showed a pattern of craniofacial, brain, and limb anomalies consistent with the acrocallosal syndrome. Both patients had a defect of the corpus callosum, macrocephaly with a protruding forehead and occiput, hypertelorism, non-horizontal palpebral fissures, a small nose, notched ear lobes, and postaxial polydactyly of the hands. The boy, in addition, had hypospadias, cryptorchidism, inguinal hernias, duplication with syndactyly of the phalanges of the big toe, and a bipartite right clavicle. The girl had an arachnoidal cyst, a calvarian defect, and digitalisation of the thumbs. Motor and mental development was retarded in both patients. This observation provides further evidence of probable autosomal recessive inheritance of the acrocallosal syndrome and widens the spectrum of clinical findings and the variability of features in this rare malformation syndrome. Images PMID:3385741

  12. Amelogenesis imperfecta and anterior open bite: Etiological, classification, clinical and management interrelationships.

    Science.gov (United States)

    Alachioti, Xanthippi Sofia; Dimopoulou, Eleni; Vlasakidou, Anatoli; Athanasiou, Athanasios E

    2014-01-01

    Although amelogenesis imperfecta is not a common dental pathological condition, its etiological, classification, clinical and management aspects have been addressed extensively in the scientific literature. Of special clinical consideration is the frequent co-existence of amelogenesis imperfecta with the anterior open bite. This paper provides an updated review on amelogenesis imperfecta as well as anterior open bite, in general, and documents the association of these two separate entities, in particular. Diagnosis and treatment of amelogenesis imperfecta patients presenting also with anterior open bite require a lengthy, comprehensive and multidisciplinary approach, which should aim to successfully address all dental, occlusal, developmental, skeletal and soft tissue problems associated with these two serious clinical conditions.

  13. Mutations in DZIP1L, which encodes a ciliary transition zone protein, cause autosomal recessive polycystic kidney disease

    Science.gov (United States)

    Lu, Hao; Galeano, Maria C. Rondón; Ott, Elisabeth; Kaeslin, Geraldine; Kausalya, P. Jaya; Kramer, Carina; Ortiz-Brüchle, Nadina; Hilger, Nadescha; Metzis, Vicki; Hiersche, Milan; Tay, Shang Yew; Tunningley, Robert; Vij, Shubha; Courtney, Andrew D.; Whittle, Belinda; Wühl, Elke; Vester, Udo; Hartleben, Björn; Neuber, Steffen; Frank, Valeska; Little, Melissa H.; Epting, Daniel; Papathanasiou, Peter; Perkins, Andrew C.; Wright, Graham D.; Hunziker, Walter; Gee, Heon Yung; Otto, Edgar A.; Zerres, Klaus; Hildebrandt, Friedhelm; Roy, Sudipto; Wicking, Carol; Bergmann, Carsten

    2017-01-01

    Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in the DAZ interacting protein 1-like (DZIP1L) gene in patients with ARPKD, findings we have further validated by loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and at the distal end of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. Consistent with a defect in the diffusion barrier, we found that the ciliary membrane translocation of the PKD proteins, polycystin-1 and −2, is compromised in DZIP1L mutant cells. Together, these data provide the first conclusive evidence that ARPKD is not a homogeneous disorder, and establishes DZIP1L as a second gene involved in its pathogenesis. PMID:28530676

  14. Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Lu, Hao; Galeano, Maria C Rondón; Ott, Elisabeth; Kaeslin, Geraldine; Kausalya, P Jaya; Kramer, Carina; Ortiz-Brüchle, Nadina; Hilger, Nadescha; Metzis, Vicki; Hiersche, Milan; Tay, Shang Yew; Tunningley, Robert; Vij, Shubha; Courtney, Andrew D; Whittle, Belinda; Wühl, Elke; Vester, Udo; Hartleben, Björn; Neuber, Steffen; Frank, Valeska; Little, Melissa H; Epting, Daniel; Papathanasiou, Peter; Perkins, Andrew C; Wright, Graham D; Hunziker, Walter; Gee, Heon Yung; Otto, Edgar A; Zerres, Klaus; Hildebrandt, Friedhelm; Roy, Sudipto; Wicking, Carol; Bergmann, Carsten

    2017-07-01

    Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and to the distal ends of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. In agreement with a defect in the diffusion barrier, we found that the ciliary-membrane translocation of the PKD proteins polycystin-1 and polycystin-2 is compromised in DZIP1L-mutant cells. Together, these data provide what is, to our knowledge, the first conclusive evidence that ARPKD is not a homogeneous disorder and further establish DZIP1L as a second gene involved in ARPKD pathogenesis.

  15. Recessive Epidermolysis Bullosa simplex- A case report

    African Journals Online (AJOL)

    Ademu

    Abstract: Background:Epidermolysis bullosa simplex (EBS) is characterized by intraepidermal blister formation, most commonly appearing in early infancy. Many variants of EBS exist; the four most common variants are inherited in an autosomal dominant fashion. The recessive forms are rare and less reported in our ...

  16. Libyan Boy with Autosomal Recessive Trait (P22-phox Defect of Chronic Granulomatous Disease

    Directory of Open Access Journals (Sweden)

    Ilka Schulze

    2006-09-01

    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency disorder of the phagocytes. In this disorder, phagocytic cells (polymorphonuclear leukocytes and monocytes cannot produce active oxygen metabolites, and therefore, cannot destroy the ingested intracellular bacteria. Clinically, patients with CGD usually have recurrent bacterial and fungal infections causing abscess and granuloma formation in the skin, lymph nodes and visceral organs.In this report, we present a boy from Libya with a rare autosomal recessive trait of CGD (defect of p22-phox who has chronic lung disease following multiple severe pneumonia attacks. The case we present suffered from bloody diarrhea since the third month of his life. He also had recurrent episodes of fever, and later, developed persistent cervical lymphadenitis and failure to gain weight. CGD is a very rare condition worldwide. It is also not recognized here in Libya, and usually not in the list of differential diagnosis for chronic pulmonary infections. We advise that pediatricians and general practitioners who treat chronic cases of lung diseases (with or without chronic diarrhea should consider primary immunodeficiency disorders in the hope that early diagnosis and treatment may prevent chronic complications especially of the respiratory tract. Furthermore, we state that, to the best of our knowledge, this is the first documented case of CGD from Libya.

  17. Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease

    DEFF Research Database (Denmark)

    Gal, Andreas; Rau, Isabella; El Matri, Leila

    2011-01-01

    heterogeneity of the trait. Using RT-PCR, PRSS56 transcripts were detected in samples derived from the human adult retina, cornea, sclera, and optic nerve. The expression of the mouse ortholog could be first detected in the eye at E17 and was maintained into adulthood. The predicted PRSS56 protein is a 603......Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we...... amino acid long secreted trypsin-like serine peptidase. The c.1066dupC is likely to result in a functional null allele, whereas the two point mutations predict the replacement of evolutionary conserved and functionally important residues. Molecular modeling of the p.Trp309Ser mutant suggests that both...

  18. Differential expression of syndecan isoforms during mouse incisor amelogenesis.

    Science.gov (United States)

    Muto, Taro; Miyoshi, Keiko; Munesue, Seiichi; Nakada, Hiroshi; Okayama, Minoru; Matsuo, Takashi; Noma, Takafumi

    2007-08-01

    Syndecans are transmembranous heparan sulfate proteoglycans (HSPGs) with covalently attached glycosaminoglycan side-chains located on the cell surface. The mammalian syndecan family is composed of four types of syndecans (syndecan-1 to -4). Syndecans interact with the intracellular cytoskeleton through the cytoplasmic domains of their core proteins and membrane proteins, extracellular enzymes, growth factors, and matrix components, through their heparan-sulfate chains, to regulate developmental processes.Here, as a first step to assess the possible roles of syndecan proteins in amelogenesis, we examined the expression patterns of all syndecan isoforms in continuously growing mouse incisors, in which we can overview major differentiation stages of amelogenesis at a glance. Understanding the expression domain of each syndecan isoform during specific developmental stages seems useful for investigating their physiological roles in amelogenesis. Immunohistochemical analysis of syndecan core proteins in the lower incisors from postnatal day 1 mice revealed spatially and temporally specific expression patterns, with syndecan-1 expressed in undifferentiated epithelial and mesenchymal cells, and syndecan-2, -3, and -4 in more differentiated cells. These findings suggest that each syndecan isoform functions distinctly during the amelogenesis of the incisors of mice.

  19. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability

    Science.gov (United States)

    Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J. M.; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D. James; Carter, Melissa T.; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B.

    2015-01-01

    Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability. PMID:26206890

  20. Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family.

    Science.gov (United States)

    Zobor, Ditta; Balousha, Ghassan; Baumann, Britta; Wissinger, Bernd

    2014-01-01

    Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression

  1. Prevalence of GJB2 Mutations in Affected Individuals from United Arab Emirates with Autosomal Recessive Nonsyndromic Hearing Loss.

    Science.gov (United States)

    Tlili, Abdelaziz; Al Mutery, Abdullah; Kamal Eddine Ahmad Mohamed, Walaa; Mahfood, Mona; Hadj Kacem, Hassen

    2017-11-01

    Mutations in the gap junction protein beta 2 (GJB2) gene are responsible for more cases of nonsyndromic recessive hearing loss than any other gene. The purpose of our study was to evaluate the prevalence of GJB2 mutations among affected individuals from United Arab Emirates (UAE). There were 50 individuals diagnosed with hereditary hearing loss and 120 healthy individuals enrolled in the study. The Sanger sequencing method was used to screen the GJB2 coding region in all affected individuals. The c.-1G>A variant was determined by the polymerase chain reaction-restriction fragment length polymorphism method in normal individuals. Nine cases with bi-allelic mutations and three cases with mono-allelic mutations were detected in 12 out of 50 patients (24%). The homozygous mutation c.35delG was identified as the cause of hearing loss in six participants (12%). The mutation c.506G>A was identified in three affected individuals (6%). The allelic frequency (14%) and low percentage of individuals that were homozygous (2%) for the c.35delG mutation suggest that there are other genes responsible for nonsyndromic deafness in the UAE population. The results reported here are a preliminary step in collecting epidemiological data regarding autosomal recessive nonsyndromic hearing loss related to GJB2 gene mutations among the UAE population. The c.35delG mutation of the GJB2 gene is the most frequently seen causative mutation in the UAE and is followed by the p.Cys169Tyr mutation.

  2. Dominant versus recessive traits conveyed by allelic mutations - to what extent is nonsense-mediated decay involved?

    NARCIS (Netherlands)

    Ben-Shachar, S.; Khajavi, M.; Withers, M.A.; Shaw, C.A.; Bokhoven, J.H.L.M. van; Brunner, H.G.; Lupski, J.R.

    2009-01-01

    Mutations in ROR2, encoding a receptor tyrosine kinase, can cause autosomal recessive Robinow syndrome (RRS), a severe skeletal dysplasia with limb shortening, brachydactyly, and a dysmorphic facial appearance. Other mutations in ROR2 result in the autosomal dominant disease, brachydactyly type B

  3. Possible linkage of SP6 transcriptional activity with amelogenesis by protein stabilization.

    Science.gov (United States)

    Utami, Trianna W; Miyoshi, Keiko; Hagita, Hiroko; Yanuaryska, Ryna Dwi; Horiguchi, Taigo; Noma, Takafumi

    2011-01-01

    Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis) are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell-type-specific manner. Sp6-deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long-term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis.

  4. Possible Linkage of SP6 Transcriptional Activity with Amelogenesis by Protein Stabilization

    Directory of Open Access Journals (Sweden)

    Trianna W. Utami

    2011-01-01

    Full Text Available Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell-type-specific manner. Sp6-deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long-term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis.

  5. Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases.

    Science.gov (United States)

    Bhatia, Shannu K; Hunter, M Lindsay; Ashley, Paul F

    2015-12-01

    Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically.

  6. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar

    2013-01-01

    Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  7. Naturally- and experimentally-designed restorations of the Parkin gene deficit in autosomal recessive juvenile parkinsonism

    International Nuclear Information System (INIS)

    Asai, Hirohide; Hirano, Makito; Kiriyama, Takao; Ikeda, Masanori; Ueno, Satoshi

    2010-01-01

    Intranuclear events due to mutations in the Parkin gene remain elusive in autosomal recessive juvenile parkinsonism (ARJP). We identified a mutant PARKIN protein in fibroblast cultures from a pair of siblings with ARJP who were homozygous for the exon 4-deleted Parkin gene. Disease was mild in one patient and debilitating in the other. The detected mutant, encoded by a transcript lacking exon 3 as well as exon 4, is an in-frame deletion that removes 121 aa, resulting in a 344-aa protein (PaDel3,4). Cell culture and transfection studies revealed negative correlations between expression levels of PaDel3,4 and those of cell cycle proteins, including cyclin E, CDK2, ppRb, and E2F-1, and demonstrated that GFP-PaDel3,4 entered nucleus and ubiquitinated cyclin E as a part of SCF hSel-10 ligase complex in the patient cells. In addition, nuclear localization signal-tagged PaDel3,4 expressed in the transfected patient cells most effectively ubiquitinated cyclin E and reduced DNA damage, protecting cells from oxidative stress. Antisense-oligonucleotide treatment promoted skipping of exon 3 and thus generated PaDel3,4, increasing cell survival. Collectively, we propose that naturally- and experimentally-induced exon skipping at least partly restores the mutant Parkin gene deficit, providing a molecular basis for the development of therapeutic exon skipping.

  8. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

    Science.gov (United States)

    Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J M; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D James; Carter, Melissa T; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B

    2015-10-15

    Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.

    Science.gov (United States)

    Ávila-Fernández, Almudena; Cantalapiedra, Diego; Aller, Elena; Vallespín, Elena; Aguirre-Lambán, Jana; Blanco-Kelly, Fiona; Corton, M; Riveiro-Álvarez, Rosa; Allikmets, Rando; Trujillo-Tiebas, María José; Millán, José M; Cremers, Frans P M; Ayuso, Carmen

    2010-12-03

    Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations in 272 Spanish families using a genotyping microarray. 272 unrelated Spanish families, 107 with autosomal recessive RP (arRP) and 165 with sporadic RP (sRP), were studied using the APEX genotyping microarray. The families were also classified by clinical criteria: 86 juveniles and 186 typical RP families. Haplotype and sequence analysis were performed to identify the second mutated allele. At least one-gene variant was found in 14% and 16% of the juvenile and typical RP groups respectively. Further study identified four new mutations, providing both causative changes in 11% of the families. Retinol Dehydrogenase 12 (RDH12) was the most frequently mutated gene in the juvenile RP group, and Usher Syndrome 2A (USH2A) and Ceramide Kinase-Like (CERKL) were the most frequently mutated genes in the typical RP group. The only variant found in CERKL was p.Arg257Stop, the most frequent mutation. The genotyping microarray combined with segregation and sequence analysis allowed us to identify the causative mutations in 11% of the families. Due to the low number of characterized families, this approach should be used in tandem with other techniques.

  10. Autosomal dominant syndrome resembling Coffin-Siris syndrome.

    Science.gov (United States)

    Flynn, Maureen A; Milunsky, Jeff M

    2006-06-15

    Coffin-Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin-Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin-Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin-Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin-Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature. Copyright 2006 Wiley-Liss, Inc.

  11. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Wang, Xin; Zhao, Yuming; Yang, Yuan; Qin, Man

    2015-01-01

    Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  12. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI. Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB, while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16 in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11 in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  13. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Barbara Gasse

    2017-06-01

    Full Text Available Amelogenesis imperfecta (AI designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20 produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues, pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  14. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta.

    Science.gov (United States)

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene ( MMP20 ) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  15. Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification

    Science.gov (United States)

    Janson, Marleen M.; Roesler, Mark R.; Avner, Ellis D.; Strawn, Estil Y.; Bick, David P.

    2010-01-01

    Purpose To develop a reliable preimplantation genetic diagnosis protocol for couples who both carry a mutant PKHD1 gene wishing to conceive children unaffected with autosomal recessive polycystic kidney disease (ARPKD). Methods Development of a unique protocol for preimplantation genetic testing using whole genome amplification of single blastomeres by multiple displacement amplification (MDA), and haplotype analysis with novel short tandem repeat (STR) markers from the PKHD1 gene and flanking sequences, and a case report of successful utilization of the protocol followed by successful IVF resulting in the birth of an infant unaffected with ARPKD. Results We have developed 20 polymorphic STR markers suitable for linkage analysis of ARPKD. These linked STR markers have enabled unambiguous identification of the PKHD1 haplotypes of embryos produced by at-risk couples. Conclusions We have developed a reliable protocol for preimplantation genetic diagnosis of ARPKD using single-cell MDA products for PKHD1 haplotyping. PMID:20490649

  16. Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases.

    Science.gov (United States)

    Mallaret, Martial; Renaud, Mathilde; Redin, Claire; Drouot, Nathalie; Muller, Jean; Severac, Francois; Mandel, Jean Louis; Hamza, Wahiba; Benhassine, Traki; Ali-Pacha, Lamia; Tazir, Meriem; Durr, Alexandra; Monin, Marie-Lorraine; Mignot, Cyril; Charles, Perrine; Van Maldergem, Lionel; Chamard, Ludivine; Thauvin-Robinet, Christel; Laugel, Vincent; Burglen, Lydie; Calvas, Patrick; Fleury, Marie-Céline; Tranchant, Christine; Anheim, Mathieu; Koenig, Michel

    2016-07-01

    Establishing a molecular diagnosis of autosomal recessive cerebellar ataxias (ARCA) is challenging due to phenotype and genotype heterogeneity. We report the validation of a previously published clinical practice-based algorithm to diagnose ARCA. Two assessors performed a blind analysis to determine the most probable mutated gene based on comprehensive clinical and paraclinical data, without knowing the molecular diagnosis of 23 patients diagnosed by targeted capture of 57 ataxia genes and high-throughput sequencing coming from a 145 patients series. The correct gene was predicted in 61 and 78 % of the cases by the two assessors, respectively. There was a high inter-rater agreement [K = 0.85 (0.55-0.98) p < 0.001] confirming the algorithm's reproducibility. Phenotyping patients with proper clinical examination, imaging, biochemical investigations and nerve conduction studies remain crucial for the guidance of molecular analysis and to interpret next generation sequencing results. The proposed algorithm should be helpful for diagnosing ARCA in clinical practice.

  17. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid. © The Author 2014. Published by Oxford University Press.

  18. Genetics of recessive cognitive disorders

    OpenAIRE

    Musante, Luciana; Ropers, H. Hilger

    2014-01-01

    Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elu...

  19. Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11)

    NARCIS (Netherlands)

    Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

    2004-01-01

    Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

  20. Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).

    NARCIS (Netherlands)

    Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

    2004-01-01

    Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

  1. A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

    Science.gov (United States)

    Taghavi, Shaghayegh; Chaouni, Rita; Tafakhori, Abbas; Azcona, Luis J; Firouzabadi, Saghar Ghasemi; Omrani, Mir Davood; Jamshidi, Javad; Emamalizadeh, Babak; Shahidi, Gholam Ali; Ahmadi, Mona; Habibi, Seyed Amir Hassan; Ahmadifard, Azadeh; Fazeli, Atena; Motallebi, Marzieh; Petramfar, Peyman; Askarpour, Saeed; Askarpour, Shiva; Shahmohammadibeni, Hossein Ali; Shahmohammadibeni, Neda; Eftekhari, Hajar; Shafiei Zarneh, Amir Ehtesham; Mohammadihosseinabad, Saeed; Khorrami, Mehdi; Najmi, Safa; Chitsaz, Ahmad; Shokraeian, Parasto; Ehsanbakhsh, Hossein; Rezaeidian, Jalal; Ebrahimi Rad, Reza; Madadi, Faranak; Andarva, Monavvar; Alehabib, Elham; Atakhorrami, Minoo; Mortazavi, Seyed Erfan; Azimzadeh, Zahra; Bayat, Mahdis; Besharati, Amir Mohammad; Harati-Ghavi, Mohammad Ali; Omidvari, Samareh; Dehghani-Tafti, Zahra; Mohammadi, Faraz; Mohammad Hossein Pour, Banafsheh; Noorollahi Moghaddam, Hamid; Esmaili Shandiz, Ehsan; Habibi, Arman; Taherian-Esfahani, Zahra; Darvish, Hossein; Paisán-Ruiz, Coro

    2018-04-01

    In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.

  2. Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis

    Science.gov (United States)

    Ullah, Rahim; Ansar, Muhammad; Durrani, Zaka Ullah; Lee, Kwanghyuk; Santos-Cortez, Regie Lyn P.; Muhammad, Dost; Ali, Mahboob; Zia, Muhammad; Ayub, Muhammad; Khan, Suliman; Smith, Josh D.; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael; Leal, Suzanne M.; Ahmad, Wasim

    2016-01-01

    Background Ichthyoses are clinically characterized by scaling or hyperkeratosis of the skin or both. It can be an isolated condition limited to the skin or appear secondarily with involvement of other cutaneous or systemic abnormalities. Methods The present study investigated clinical and molecular characterization of three consanguineous families (A, B, C) segregating two different forms of autosomal recessive congenital ichthyosis (ARCI). Linkage in three consanguineous families (A, B, C) segregating two different forms of ARCI was searched by typing microsatellite and single nucleotide polymorphism marker analysis. Sequencing of the two genes TGM1 and ALOXE3 was performed by the dideoxy chain termination method. Results Genome-wide linkage analysis established linkage in family A to TGM1 gene on chromosome 14q11 and in families B and C to ALOXE3 gene on chromosome 17p13. Subsequently, sequencing of these genes using samples from affected family members led to the identification of three novel mutations: a missense variant p.Trp455Arg in TGM1 (family A); a nonsense variant p.Arg140* in ALOXE3 (family B); and a complex rearrangement in ALOXE3 (family C). Conclusion The present study further extends the spectrum of mutations in the two genes involved in causing ARCI. Characterizing the clinical spectrum resulting from mutations in the TGM1 and ALOXE3 genes will improve diagnosis and may direct clinical care of the family members. PMID:26578203

  3. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

    Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

  4. Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Satoshi Katagiri

    Full Text Available OBJECTIVE: The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP in the Japanese population. METHODS: In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all CNGA1 exons of the other 69 RP patients were performed. RESULTS: Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of CNGA1 (four patients, EYS (three patients and SAG (one patient in eight patients and potential disease-causing gene variants of USH2A (two patients, EYS (one patient, TULP1 (one patient and C2orf71 (one patient in five patients. Screening of an additional 69 arRP/spRP patients for the CNGA1 gene mutation revealed one patient with a homozygous mutation. CONCLUSIONS: This is the first identification of CNGA1 mutations in arRP Japanese patients. The frequency of CNGA1 gene mutation was 5.1% (5/99 patients. CNGA1 mutations are one of the most frequent arRP-causing mutations in Japanese patients.

  5. Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy. A clinical and computed tomographic study

    Energy Technology Data Exchange (ETDEWEB)

    Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie

    1987-02-01

    Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings center dot adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT.

  6. Amelogrenesis Imperfekta Herediter

    OpenAIRE

    Pane, Evalyn MD.

    2008-01-01

    Amelogenesis imperfekta merupakan suatu istilah untuk sejumlah gangguan perkembangan enamel yang bersifat herediter, Gangguan ini dapat berupa herediter autosomal dominan, herediter autosomal resesif, herediter sex dominan dan herediter sex resesif. Menurut Witkop JC, dkk amelogenesis imperfekta dapat dibagi atas tiga tipe besar yaitu: tipe hipoplasia enamel, tipe hipokalsifikasi enamel dan tipe hipomaturasi enamel. Perbedaan hipoplasia enamel dan hipomaturasi enamel dapat dilihat se...

  7. Amelogenesis Imperfecta with Taurodontism, Microdontia, and Minor Thalassemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Fatemeh Mazhari

    2013-12-01

    Full Text Available Amelogenesis imperfecta is a group of genetic disorders that affects both the morphology and quality of tooth structure. Although the disease entity is primarily associated with abnormalities of dental and oral structures, it has been reported to be associated with a few syndromes. A 9-year-old girl with minor thalassemia referred to the Department of Pediatric Dentistry of the Mashhad Faculty of Dentistry with a complaint of sensitivity of first permanent molars. Dental findings consisted of amelogenesis imperfecta, microdontia, posterior cross bite and taurodontism. This is the first report of thalassemia accompanied with amelogenesis imperfecta. Although the patients often are non-symptomatic, the trait can be passed on to a child and if both parents carry the trait, the child could develop a more severe form of the disease; therefore, early diagnosis is important.

  8. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    Science.gov (United States)

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  9. A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.

    Science.gov (United States)

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-05-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with nonsyndromic ARMR in four sibships. Genome-wide SNP typing enabled us to map the relevant genetic defect to a 4.6 Mbp interval on chromosome 8. Haplotype analyses and copy-number studies led to the identification of a homozygous deletion partly removing TUSC3 (N33) in all patients. All obligate carriers of this family were heterozygous, but none of 192 unrelated healthy individuals from the same population carried this deletion. We excluded other disease-causing mutations in the coding regions of all genes within the linkage interval by sequencing; moreover, we verified the complete absence of a functional TUSC3 transcript in all patients through RT-PCR. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltransferase complex that catalyzes a pivotal step in the protein N-glycosylation process. Our data suggest that in contrast to other genetic defects of glycosylation, inactivation of TUSC3 causes nonsyndromic MR, a conclusion that is supported by a separate report in this issue of AJHG. TUSC3 is only the fifth gene implicated in NS-ARMR and the first for which mutations have been reported in more than one family.

  10. Amelogenesis Imperfect, Enamel Hypoplasia and Fluorosis Dental - Literature Review

    Directory of Open Access Journals (Sweden)

    Flávia Magnani Bevilacqua

    2015-12-01

    Full Text Available The developmental disorders of enamel are abnormalities of structure which can affect both dentitions. These abnormalities include amelogenesis imperfecta, enamel hypoplasia and dental fluorosis. The amelogenesis imperfecta is a hereditary change and enamel hypoplasia is a quantitative defect of enamel that occurs as a result of systemic problems, local and also inherited factors, or even the combination of them. Dental fluorosis is a hypoplasia caused by the chronic ingestion of fluoride during odontogenesis. All these anomalies have similar clinical characteristics, and it is necessary to be careful in their assessment. It is extremely important to know these abnormalities to establish a differential diagnosis and, consequently, a treatment plan, which can be set for each situation. Therefore, the purpose of this study was to review the literature regarding these three anomalies: amelogenesis imperfecta, enamel hypoplasia and dental fluorosis. It was concluded that to establish the differential diagnosis of these abnormalities as well as a proper treatment plan, it is indispensable the professional knowledge associated with the clinical examination. The examination has to consist of medical history and physical examination, and in some cases, x-ray examination.

  11. Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

    Science.gov (United States)

    Parry, David A; Smith, Claire E L; El-Sayed, Walid; Poulter, James A; Shore, Roger C; Logan, Clare V; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Harada, Akihiro; Zhang, Hong; Koruyucu, Mine; Seymen, Figen; Hu, Jan C-C; Simmer, James P; Ahmed, Mushtaq; Jafri, Hussain; Johnson, Colin A; Inglehearn, Chris F; Mighell, Alan J

    2016-10-06

    Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion, and a missense variant) were predicted to result in loss of function. GPR68 encodes a proton-sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3.

    Science.gov (United States)

    Klebe, Stephan; Azzedine, Hamid; Durr, Alexandra; Bastien, Patrick; Bouslam, Naima; Elleuch, Nizar; Forlani, Sylvie; Charon, Celine; Koenig, Michel; Melki, Judith; Brice, Alexis; Stevanin, Giovanni

    2006-06-01

    The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped so far, and 11 responsible genes have been identified. Clinically, one distinguishes between pure and complex HSP forms which are variably associated with numerous combinations of neurological and extra-neurological signs. Less is known about autosomal recessive forms (ARHSP) since the mapped loci have been identified often in single families and account for only a small percentage of patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a consanguineous family with seven unaffected and four affected members of Algerian origin living in Eastern France with a significant multipoint lod score of 3.8. Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the Czech Republic (n = 1) were not linked to the newly identified locus thus demonstrating further genetic heterogeneity. The phenotype of the linked family consists of spastic paraparesis and peripheral neuropathy associated with slight cerebellar signs confirmed by cerebellar atrophy on one CT scan.

  13. Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach

    Science.gov (United States)

    Zimoń, Magdalena; Battaloǧlu, Esra; Parman, Yesim; Erdem, Sevim; Baets, Jonathan; De Vriendt, Els; Atkinson, Derek; Almeida-Souza, Leonardo; Deconinck, Tine; Ozes, Burcak; Goossens, Dirk; Cirak, Sebahattin; Van Damme, Philip; Shboul, Mohammad; Voit, Thomas; Van Maldergem, Lionel; Dan, Bernard; El-Khateeb, Mohammed S.; Guergueltcheva, Velina; Lopez-Laso, Eduardo; Goemans, Nathalie; Masri, Amira; Züchner, Stephan; Timmerman, Vincent; Topaloǧlu, Haluk; De Jonghe, Peter

    2016-01-01

    Autosomal recessive forms of Charcot-Marie-Tooth disease (ARCMT) are rare but severe disorders of the peripheral nervous system. Their molecular basis is poorly understood due to the extensive genetic and clinical heterogeneity, posing considerable challenges for patients, physicians, and researchers. We report on the genetic findings from a systematic study of a large collection of 174 independent ARCMT families. Initial sequencing of the three most common ARCMT genes (ganglioside-induced differentiation protein 1—GDAP1, SH3 domain and tetratricopeptide repeats-containing protein 2—SH3TC2, histidine-triad nucleotide binding protein 1—HINT1) identified pathogenic mutations in 41 patients. Subsequently, 87 selected nuclear families underwent single nucleotide polymorphism (SNP) genotyping and homozygosity mapping, followed by targeted screening of known ARCMT genes. This strategy provided molecular diagnosis to 22 % of the families. Altogether, our unbiased genetic approach identified pathogenic mutations in ten ARCMT genes in a total of 41.3 % patients. Apart from a newly described founder mutation in GDAP1, the majority of variants constitute private molecular defects. Since the gene testing was independent of the clinical phenotype of the patients, we identified mutations in patients with unusual or additional clinical features, extending the phenotypic spectrum of the SH3TC2 gene. Our study provides an overview of the ARCMT genetic landscape and proposes guidelines for tackling the genetic heterogeneity of this group of hereditary neuropathies. PMID:25231362

  14. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia.

    Science.gov (United States)

    Adaimy, Lynn; Chouery, Eliane; Megarbane, Hala; Mroueh, Salman; Delague, Valerie; Nicolas, Elsa; Belguith, Hanen; de Mazancourt, Philippe; Megarbane, Andre

    2007-10-01

    Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ~9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases.

  15. Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

    Science.gov (United States)

    Maugeri, A; Klevering, B J; Rohrschneider, K; Blankenagel, A; Brunner, H G; Deutman, A F; Hoyng, C B; Cremers, F P

    2000-10-01

    The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

  16. Molecular Basis of Human Enamel Defects

    Directory of Open Access Journals (Sweden)

    Chatzopoulos Georgios

    2014-03-01

    Full Text Available During eruption of teeth in the oral cavity, the effect of gene variations and environmental factors can result in morphological and structural changes in teeth. Amelogenesis imperfecta is a failure which is detected on the enamel of the teeth and clinical picture varies by the severity and type of the disease. Classification of the types of amelogenesis imperfecta is determined by histological, genetic, clinical and radiographic criteria. Specifically, there are 4 types of amelogenesis imperfecta (according to Witkop: hypoplastic form, hypo-maturation form, hypo-calcified form, and hypo-maturation/hypoplasia form with taurodontism and 14 subcategories. The diagnosis and classification of amelogenesis imperfecta has traditionally been based on clinical presentation or phenotype and the inheritance pattern. Several genes can be mutated and cause the disease. Millions of genes, possibly more than 10,000 genes produce proteins that regulate synthesis of enamel. Some of the genes and gene products that are likely associated with amelogenesis imperfecta are: amelogenin (AMELX, AMELY genes, ameloblastin (AMBN gene, enamelin (ENAM gene, enamelysin (MMP20 gene, kalikryn 4 (KLK 4 gene, tuftelins (Tuftelin gene, FAM83H (FAM83H gene and WDR72 (WDR72 gene. Particular attention should be given by the dentist in recognition and correlation of phenotypes with genotypes, in order to diagnose quickly and accurately such a possible disease and to prevent or treat it easily and quickly. Modern dentistry should restore these lesions in order to guarantee aesthetics and functionality, usually in collaboration with a group of dentists.

  17. Recessive omodysplasia: five new cases and review of the literature

    International Nuclear Information System (INIS)

    Elcioglu, Nursel H.; Gustavson, Karl H.; Wilkie, Andrew O.M.; Yueksel-Apak, Memune; Spranger, Juergen W.

    2004-01-01

    Autosomal recessive omodysplasia (MIM 258315) is a rare skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Fewer than 20 cases have been reported in the literature so far. The purpose of this study was to more clearly describe the clinical and radiographic phenotypes and their changes with age. Five new patients, including two sibs, with autosomal recessive omodysplasia are presented. Clinical features are rhizomelic dwarfism with limited extension of elbows and knees and a distinct face with a short nose, depressed nasal bridge, long philtrum, midline haemangiomas in infants and cryptorchidism in males. Radiological findings are distal hypoplasia of the short humerus and femur with characteristic radial dislocation and radioulnar diastasis. Based on a review of these and 16 previously reported patients, the regressive nature of the humerofemoral changes and the obvious male predominance are stressed. Phenotypic similarities with the atelosteogenesis group of disorders and with diastrophic dysplasia suggest common pathogenetic mechanisms. (orig.)

  18. A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance

    Directory of Open Access Journals (Sweden)

    Ali Bassam R

    2012-05-01

    Full Text Available Abstract Background We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26. Methods In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation. Results Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia. Conclusions We report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.

  19. Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta.

    Science.gov (United States)

    Kim, Y-J; Seymen, F; Koruyucu, M; Kasimoglu, Y; Gencay, K; Shin, T J; Hyun, H-K; Lee, Z H; Kim, J-W

    2016-05-01

    To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The proband's mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes. © 2016 The Authors. Oral Diseases Published by John Wiley & Sons Ltd.

  20. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

    International Nuclear Information System (INIS)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-01-01

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management

  1. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali [Dept. of Conservative Dentistry and Endodontics, Manubhai Patel Dental College, Maharaja Krishnakumarsinhji Bhavnagar University, Vadodara (India)

    2015-09-15

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  2. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

    Science.gov (United States)

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-09-01

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  3. Enamel formation and amelogenesis imperfecta.

    Science.gov (United States)

    Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

    2007-01-01

    Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel. Copyright 2007 S. Karger AG, Basel.

  4. Circadian rhythms regulate amelogenesis.

    Science.gov (United States)

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

    2013-07-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India

    Directory of Open Access Journals (Sweden)

    A P Javed

    2013-01-01

    Full Text Available Epidermolysis bullosa (EB is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  6. Four siblings with distal renal tubular acidosis and nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial appearance: a possible new autosomal recessive syndrome.

    Science.gov (United States)

    Faqeih, Eissa; Al-Akash, Samhar I; Sakati, Nadia; Teebi, Prof Ahmad S

    2007-09-01

    We report on four siblings (three males, one female) born to first cousin Arab parents with the constellation of distal renal tubular acidosis (RTA), small kidneys, nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial features. They presented with early developmental delay with subsequent severe mental, behavioral and social impairment and autistic-like features. Their facial features are unique with prominent cheeks, well-defined philtrum, large bulbous nose, V-shaped upper lip border, full lower lip, open mouth with protruded tongue, and pits on the ear lobule. All had proteinuria, hypercalciuria, hypercalcemia, and normal anion-gap metabolic acidosis. Renal ultrasound examinations revealed small kidneys, with varying degrees of hyperechogenicity and nephrocalcinosis. Additional findings included dilated ventricles and cerebral demyelination on brain imaging studies. Other than distal RTA, common causes of nephrocalcinosis were excluded. The constellation of features in this family currently likely represents a possibly new autosomal recessive syndrome providing further evidence of heterogeneity of nephrocalcinosis syndromes. Copyright 2007 Wiley-Liss, Inc.

  7. Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; El-Khayat, Hamed A; Eid, Ola M; Saba, Soliman; Farag, Mona K; Saleem, Sahar N; Gaber, Khaled R

    2015-05-01

    The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed. © 2015 Wiley Periodicals, Inc.

  8. Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A.

    Science.gov (United States)

    Disertori, Marcello; Quintarelli, Silvia; Grasso, Maurizia; Pilotto, Andrea; Narula, Nupoor; Favalli, Valentina; Canclini, Camilla; Diegoli, Marta; Mazzola, Silvia; Marini, Massimiliano; Del Greco, Maurizio; Bonmassari, Roberto; Masè, Michela; Ravelli, Flavia; Specchia, Claudia; Arbustini, Eloisa

    2013-02-01

    Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

  9. Radiation effect on the stages of amelogenesis in the rat incisor

    International Nuclear Information System (INIS)

    Choi, Hyun Bae; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

    1997-01-01

    The purpose of this study was to investigate the radiation effect on the stages of amelogenesis. Twenty 11-day-old rats which were irradiated by 4 GY of gamma radiation on the 19th prenatal day were used for the experimental group and twenty 11-day-old rats which were not irradiated were used for the control group. The length of each zone of amelogenesis were measured on the sagittal section using a light microscopic enlargement at 400X the normal view while the morphologic changes of ameloblasts of each zone were observed electron-microscopically. The obtained results were as followed : 1. The length of the region of facing pulp and facing dentin of the zone of presecretion were increased by 11.5% (P 0.01). 3. The total length of the zone of amelogenesis was not changed significantly (P>0.05). 4. Electron-microscopically, enlargement of the cell membrane, rER, mitochondria, and nuclear membrane were observed. These changes were mostly severe in the zone of maturation.

  10. Genetic Linkage Analysis of the DFNB21 Locus in Autosomal Recessive Hearing Loss in Large Families from Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Mahtab Khosrofar

    2017-06-01

    Full Text Available Abstract Background: Hearing loss (HL is the most common congenital defect in humans. One or two in thousand newborn babies have prelingual hearing loss. Autosomal recessive non-syndromic hearing loss (ARNSHL is the most common form of hereditary deafness. Hearing loss is more common in the developing countries which is due to genetic and environmental (cultural -health factors reasons. HL has a wide range of clinical demonstrations including: congenital or late onset, conductive or sensory-neural, syndromic or non-syndromic hearing loss. The goal of this project is to determine the portion of the DFNB21 (TECTA in ARNSHL in families with negative GJB2 gene in Khuzestan province. Materials and Methods: We studied 21 families with ARNSHL with at least 4 patients and negative for GJB2 mutations from Khuzestan province. Genetic linkage analysis was performed using STR markers linked to DFNB21 locus. Results: Following genetic linkage analysis and haplotyping, out of 21 families with ARNSHL, one family showed linkage to the DFNB21 (TECTA locus. Conclusion: The results of this project confirm other studies in Iran and give insight into the most common loci causing ARNSHL in Iran which could be helpful in research and clinic.

  11. Autosomal recessive posterior column ataxia with retinitis pigmentosa caused by novel mutations in the FLVCR1 gene.

    Science.gov (United States)

    Shaibani, Aziz; Wong, Lee-Jun; Wei Zhang, Victor; Lewis, Richard Alan; Shinawi, Marwan

    2015-01-01

    Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive disorder characterized by severe sensory ataxia, muscle weakness and atrophy, and progressive pigmentary retinopathy. Recently, mutations in the FLVCR1 gene were described in four families with this condition. We investigated the molecular basis and studied the phenotype of PCARP in a new family. The proband is a 33-year-old woman presented with sensory polyneuropathy and retinitis pigmentosa (RP). The constellation of clinical findings with normal metabolic and genetic evaluation, including mitochondrial DNA (mtDNA) analysis and normal levels of phytanic acid and vitamin E, prompted us to seek other causes of our patient's condition. Sequencing of FLVCR1 in the proband and targeted mutation testing in her two affected siblings revealed two novel variants, c.1547G > A (p.R516Q) and c.1593+5_+8delGTAA predicted, respectively, to be highly conserved throughout evolution and affecting the normal splicing, therefore, deleterious. This study supports the pathogenic role of FLVCR1 in PCARP and expands the molecular and clinical spectra of PCARP. We show for the first time that nontransmembrane domain (TMD) mutations in the FLVCR1 can cause PCARP, suggesting different mechanisms for pathogenicity. Our clinical data reveal that impaired sensation can be part of the phenotypic spectrum of PCARP. This study along with previously reported cases suggests that targeted sequencing of the FLVCR1 gene should be considered in patients with severe sensory ataxia, RP, and peripheral sensory neuropathy.

  12. Preimplantation genetic diagnosis for a Chinese family with autosomal recessive Meckel-Gruber syndrome type 3 (MKS3.

    Directory of Open Access Journals (Sweden)

    Yanping Lu

    Full Text Available Meckel-Gruber syndrome type 3 is an autosomal recessive genetic defect caused by mutations in TMEM67 gene. In our previous study, we have identified a homozygous TMEM67 mutation in a Chinese family exhibiting clinical characteristics of MKS3, which provided a ground for further PGD procedure. Here we report the development and the first clinical application of the PGD for this MKS3 family. Molecular analysis protocol for clinical PGD procedure was established using 50 single cells in pre-clinical set-up. After whole genomic amplification by multiple displacement amplification with the DNA from single cells, three techniques were applied simultaneously to increase the accuracy and reliability of genetic diagnosis in single blastomere, including real-time PCR with Taq Man-MGB probe, haplotype analysis with polymorphic STR markers and Sanger sequencing. In the clinical PGD cycle, nine embryos at cleavage-stage were biopsied and subjected to genetic diagnosis. Two embryos diagnosed as free of TMEM67 mutation were transferred and one achieving normal pregnancy. Non-invasive prenatal assessment of trisomy 13, 18 and 21 by multiplex DNA sequencing at 18 weeks' gestation excluded the aneuploidy of the analyzed chromosomes. A healthy boy was delivered by cesarean section at 39 weeks' gestation. DNA sequencing from his cord blood confirmed the result of genetic analysis in the PGD cycle. The protocol developed in this study was proved to be rapid and safe for the detection of monogenic mutations in clinical PGD cycle.

  13. SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system.

    Science.gov (United States)

    Brons, A-K; Henthorn, P S; Raj, K; Fitzgerald, C A; Liu, J; Sewell, A C; Giger, U

    2013-01-01

    Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds. To determine urinary cystine concentrations, inheritance, and mutations in the SLC3A1 and SLC7A9 genes associated with cystinuria in 3 breeds. Mixed and purebred Labrador Retrievers (n = 6), Australian Cattle Dogs (6), Miniature Pinschers (4), and 1 mixed breed dog with cystine urolithiasis, relatives and control dogs. Urinary cystinuria and aminoaciduria was assessed and exons of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA. In each breed, male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC3A1 (c.350delG) resulting in a premature stop codon was identified in autosomal-recessive (AR) cystinuria in Labrador Retrievers and mixed breed dogs. A 6 bp deletion (c.1095_1100del) removing 2 threonines in SLC3A1 was found in autosomal-dominant (AD) cystinuria with a more severe phenotype in homozygous than in heterozygous Australian Cattle Dogs. A missense mutation in SLC7A9 (c.964G>A) was discovered in AD cystinuria in Miniature Pinschers with only heterozygous affected dogs observed to date. Breed-specific DNA tests were developed, but the prevalence of each mutation remains unknown. These studies describe the first AD inheritance and the first putative SLC7A9 mutation to cause cystinuria in dogs and expand our understanding of this phenotypically and genetically heterogeneous disease, leading to a new classification system for canine cystinuria and better therapeutic management and genetic control in these breeds. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  14. Identification of a novel FAM83H mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta.

    Science.gov (United States)

    Hyun, H-K; Lee, S-K; Lee, K-E; Kang, H-Y; Kim, E-J; Choung, P-H; Kim, J-W

    2009-11-01

    To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known FAM83H mutation. Mutational screening of the FAM83H on the basis of candidate gene approach was performed. All exons and exon-intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value. A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of FAM83H, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control. Mutational analysis revealed a novel mutation in FAM83H gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.

  15. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects.

    Directory of Open Access Journals (Sweden)

    Jinglan Zhang

    2016-04-01

    Full Text Available Genetic leukoencephalopathies (gLEs are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS. The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES, we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G, as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026. VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting and CORVET (class C core vacuole/endosome tethering protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway.

  16. Amelogenesis Imperfecta; Genes, Proteins, and Pathways

    Directory of Open Access Journals (Sweden)

    Claire E. L. Smith

    2017-06-01

    Full Text Available Amelogenesis imperfecta (AI is the name given to a heterogeneous group of conditions characterized by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discolored, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties, and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light. Mutations in the gene AMELX, encoding an extracellular matrix protein secreted by ameloblasts during enamel formation, were first identified as a cause of AI in 1991. Since then, mutations in at least eighteen genes have been shown to cause AI presenting in isolation of other health problems, with many more implicated in syndromic AI. Some of the encoded proteins have well documented roles in amelogenesis, acting as enamel matrix proteins or the proteases that degrade them, cell adhesion molecules or regulators of calcium homeostasis. However, for others, function is less clear and further research is needed to understand the pathways and processes essential for the development of healthy enamel. Here, we review the genes and mutations underlying AI presenting in isolation of other health problems, the proteins they encode and knowledge of their roles in amelogenesis, combining evidence from human phenotypes, inheritance patterns, mouse models, and in vitro studies. An LOVD resource (http://dna2.leeds.ac.uk/LOVD/ containing all published gene mutations for AI presenting in isolation of other health problems is described. We use this resource to identify trends in the genes and mutations reported to cause AI in the 270 families for which molecular diagnoses have been reported by 23rd May 2017. Finally we discuss the potential value of the translation of AI genetics to clinical care with improved patient pathways and

  17. Amelogenesis Imperfecta; Genes, Proteins, and Pathways.

    Science.gov (United States)

    Smith, Claire E L; Poulter, James A; Antanaviciute, Agne; Kirkham, Jennifer; Brookes, Steven J; Inglehearn, Chris F; Mighell, Alan J

    2017-01-01

    Amelogenesis imperfecta (AI) is the name given to a heterogeneous group of conditions characterized by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discolored, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties, and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light. Mutations in the gene AMELX , encoding an extracellular matrix protein secreted by ameloblasts during enamel formation, were first identified as a cause of AI in 1991. Since then, mutations in at least eighteen genes have been shown to cause AI presenting in isolation of other health problems, with many more implicated in syndromic AI. Some of the encoded proteins have well documented roles in amelogenesis, acting as enamel matrix proteins or the proteases that degrade them, cell adhesion molecules or regulators of calcium homeostasis. However, for others, function is less clear and further research is needed to understand the pathways and processes essential for the development of healthy enamel. Here, we review the genes and mutations underlying AI presenting in isolation of other health problems, the proteins they encode and knowledge of their roles in amelogenesis, combining evidence from human phenotypes, inheritance patterns, mouse models, and in vitro studies. An LOVD resource (http://dna2.leeds.ac.uk/LOVD/) containing all published gene mutations for AI presenting in isolation of other health problems is described. We use this resource to identify trends in the genes and mutations reported to cause AI in the 270 families for which molecular diagnoses have been reported by 23rd May 2017. Finally we discuss the potential value of the translation of AI genetics to clinical care with improved patient pathways and speculate on the

  18. Computational analysis of TRAPPC9: candidate gene for autosomal recessive non-syndromic mental retardation.

    Science.gov (United States)

    Khattak, Naureen Aslam; Mir, Asif

    2014-01-01

    Mental retardation (MR)/ intellectual disability (ID) is a neuro-developmental disorder characterized by a low intellectual quotient (IQ) and deficits in adaptive behavior related to everyday life tasks such as delayed language acquisition, social skills or self-help skills with onset before age 18. To date, a few genes (PRSS12, CRBN, CC2D1A, GRIK2, TUSC3, TRAPPC9, TECR, ST3GAL3, MED23, MAN1B1, NSUN1) for autosomal-recessive forms of non syndromic MR (NS-ARMR) have been identified and established in various families with ID. The recently reported candidate gene TRAPPC9 was selected for computational analysis to explore its potentially important role in pathology as it is the only gene for ID reported in more than five different familial cases worldwide. YASARA (12.4.1) was utilized to generate three dimensional structures of the candidate gene TRAPPC9. Hybrid structure prediction was employed. Crystal Structure of a Conserved Metalloprotein From Bacillus Cereus (3D19-C) was selected as best suitable template using position-specific iteration-BLAST. Template (3D19-C) parameters were based on E-value, Z-score and resolution and quality score of 0.32, -1.152, 2.30°A and 0.684 respectively. Model reliability showed 93.1% residues placed in the most favored region with 96.684 quality factor, and overall 0.20 G-factor (dihedrals 0.06 and covalent 0.39 respectively). Protein-Protein docking analysis demonstrated that TRAPPC9 showed strong interactions of the amino acid residues S(253), S(251), Y(256), G(243), D(131) with R(105), Q(425), W(226), N(255), S(233), its functional partner 1KBKB. Protein-protein interacting residues could facilitate the exploration of structural and functional outcomes of wild type and mutated TRAPCC9 protein. Actively involved residues can be used to elucidate the binding properties of the protein, and to develop drug therapy for NS-ARMR patients.

  19. Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome.

    Science.gov (United States)

    Cabral, Rita M; Kurban, Mazen; Wajid, Muhammad; Shimomura, Yutaka; Petukhova, Lynn; Christiano, Angela M

    2012-04-01

    Generalized peeling skin syndrome (PSS) is an autosomal recessive genodermatosis characterized by lifelong, continuous shedding of the upper epidermis. Using whole-genome homozygozity mapping and whole-exome sequencing, we identified a novel homozygous missense mutation (c.229C>T, R77W) within the CHST8 gene, in a large consanguineous family with non-inflammatory PSS type A. CHST8 encodes a Golgi transmembrane N-acetylgalactosamine-4-O-sulfotransferase (GalNAc4-ST1), which we show by immunofluorescence staining to be expressed throughout normal epidermis. A colorimetric assay for total sulfated glycosaminoglycan (GAG) quantification, comparing human keratinocytes (CCD1106 KERTr) expressing wild type and mutant recombinant GalNAc4-ST1, revealed decreased levels of total sulfated GAGs in cells expressing mutant GalNAc4-ST1, suggesting loss of function. Western blotting revealed lower expression levels of mutant recombinant GalNAc4-ST1 compared to wild type, suggesting that accelerated degradation may result in loss of function, leading to PSS type A. This is the first report describing a mutation as the cause of PSS type A. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes

    DEFF Research Database (Denmark)

    Duchatelet, Sabine; Ostergaard, Elsebet; Cortes, Dina

    2005-01-01

    Eiken syndrome is a rare autosomal recessive skeletal dysplasia. We identified a truncation mutation in the C-terminal cytoplasmic tail of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) type 1 receptor (PTHR1) gene as the cause of this syndrome. Eiken syndrome differs from Jansen...

  1. Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Katsuhiro Hosono

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic disease including autosomal recessive (ar, autosomal dominant (ad, and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog, which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation. Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2 and c.8868C>A (p.Y2956X, were identified in 16 patients and accounted for 57.1% (20/35 alleles of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing

  2. Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat.

    Science.gov (United States)

    Adiningrat, A; Tanimura, A; Miyoshi, K; Hagita, H; Yanuaryska, R D; Arinawati, D Y; Horiguchi, T; Noma, T

    2016-03-01

    Disruption of the third zinc finger domain of specificity protein 6 (SP6) presents an enamel-specific defect in a rat model of amelogenesis imperfecta (AMI rats). To understand the molecular basis of amelogenesis imperfecta caused by the Sp6 mutation, we established and characterized AMI-derived rat dental epithelial (ARE) cells. ARE cell clones were isolated from the mandibular incisors of AMI rats, and amelogenesis-related gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Localization of wild-type SP6 (SP6WT) and mutant-type SP6 (SP6AMI) was analyzed by immunocytochemistry. SP6 transcriptional activity was monitored by rho-associated protein kinase 1 (Rock1) promoter activity with its specific binding to the promoter region in dental (G5 and ARE) and non-dental (COS-7) epithelial cells. Isolated ARE cells were varied in morphology and gene expression. Both SP6WT and SP6AMI were mainly detected in nuclei. The promoter analysis revealed that SP6WT and SP6AMI enhanced Rock1 promoter activity in G5 cells but that enhancement by SP6AMI was weaker, whereas no enhancement was observed in the ARE and COS-7 cells, even though SP6WT and SP6AMI bound to the promoter in all instances. ARE cell clones can provide a useful in vitro model to study the mechanism of SP6-mediated amelogenesis imperfecta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis.

    Science.gov (United States)

    Bardet, Claire; Ribes, Sandy; Wu, Yong; Diallo, Mamadou Tidiane; Salmon, Benjamin; Breiderhoff, Tilman; Houillier, Pascal; Müller, Dominik; Chaussain, Catherine

    2017-01-01

    Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

  4. Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

    Directory of Open Access Journals (Sweden)

    Claire Bardet

    2017-05-01

    Full Text Available Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL. Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC, were recently shown to be also involved in Amelogenesis Imperfecta (AI. In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

  5. The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients.

    Science.gov (United States)

    Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, Miho; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

    2014-09-01

    Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.

  6. Simultaneous Occurence of an Autosomal Dominant Inherited MSX1 Mutation and an X-linked Recessive Inherited EDA Mutation in One Chinese Family with Non-syndromic Oligodontia.

    Science.gov (United States)

    Zhang, Xiao Xia; Wong, Sing Wai; Han, Dong; Feng, Hai Lan

    2015-01-01

    To describe the simultaneous occurence of an autosomal dominant inherited MSX1 mutation and an X-linked recessive inherited EDA mutation in one Chinese family with nonsyndromic oligodontia. Clinical data of characteristics of tooth agenesis were collected. MSX1 and EDA gene mutations were detected in a Chinese family of non-syndromic oligodontia. Mild hypodontia in the parents and severe oligodontia in the son was recorded. A novel missense heterozygous mutation c.517C>A (p.Arg173Ser) was detected in the MSX1 gene in the boy and the father. A homozygous missense mutation c.1001G>A (p.Arg334His) was detected in the EDA gene in the boy and the same mutant occurred heterozygously in the mother. Simultaneous occurence of two different gene mutations with different inheritence patterns, which both caused oligodontia, which occurred in one subject and in one family, was reported.

  7. Diagnosis, treatment planning, and full-mouth rehabilitation in a case of amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Mayuri Naik

    2018-01-01

    Full Text Available Amelogenesis imperfecta is a genetic condition affecting the teeth resulting in aberrations of the structure and clinical appearance of enamel. The treatment of amelogenesis imperfecta involves a multidisciplinary treatment approach requiring a comprehensive examination, diagnosis, and effective treatment planning strategy along with satisfaction of patient-related factors. The clinical case described here involves judicious involvement of different disciplines to formulate a treatment plan best suitable to confirm with the patient's needs and expectations, at the same time maintaining the integrity and harmony of associated hard and soft tissues.

  8. Radiation effect on the stages of amelogenesis in the rat incisor

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyun Bae; Choi, Soon Chul; Park, Tae Won; You, Dong Soo [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1997-02-15

    The purpose of this study was to investigate the radiation effect on the stages of amelogenesis. Twenty 11-day-old rats which were irradiated by 4 GY of gamma radiation on the 19th prenatal day were used for the experimental group and twenty 11-day-old rats which were not irradiated were used for the control group. The length of each zone of amelogenesis were measured on the sagittal section using a light microscopic enlargement at 400X the normal view while the morphologic changes of ameloblasts of each zone were observed electron-microscopically. The obtained results were as followed : 1. The length of the region of facing pulp and facing dentin of the zone of presecretion were increased by 11.5% (P<0.01) and 17.7% (P<0.01), respectively. 2. The length of the zone of secretion was increased by 17.3% (P<0.01), but the zone of maturation was decreased by 15.3% (P>0.01). 3. The total length of the zone of amelogenesis was not changed significantly (P>0.05). 4. Electron-microscopically, enlargement of the cell membrane, rER, mitochondria, and nuclear membrane were observed. These changes were mostly severe in the zone of maturation.

  9. EDAR mutation in autosomal dominant hypohidrotic ectodermal dysplasia in two Swedish families

    Directory of Open Access Journals (Sweden)

    Schmitt-Egenolf Marcus

    2006-11-01

    Full Text Available Abstract Background Hypohidrotic ectodermal dysplasia (HED is a genetic disorder characterized by defective development of teeth, hair, nails and eccrine sweat glands. Both autosomal dominant and autosomal recessive forms of HED have previously been linked to mutations in the ectodysplasin 1 anhidrotic receptor (EDAR protein that plays an important role during embryogenesis. Methods The coding DNA sequence of the EDAR gene was analyzed in two large Swedish three-generational families with autosomal dominant HED. Results A non-sense C to T mutation in exon 12 was identified in both families. This disease-specific mutation changes an arginine amino acid in position 358 of the EDAR protein into a stop codon (p.Arg358X, thereby truncating the protein. In addition to the causative mutation two polymorphisms, not associated with the HED disorder, were also found in the EDAR gene. Conclusion The finding of the p.Arg358X mutation in the Swedish families is the first corroboration of a previously described observation in an American family. Thus, our study strengthens the role of this particular mutation in the aetiology of autosomal dominant HED and confirms the importance of EDAR for the development of HED.

  10. Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene.

    Science.gov (United States)

    Sandberg, Michael A; Rosner, Bernard; Weigel-DiFranco, Carol; McGee, Terri L; Dryja, Thaddeus P; Berson, Eliot L

    2008-12-01

    To estimate the mean rates of ocular function loss in patients with autosomal recessive retinitis pigmentosa due to USH2A mutations. In 125 patients with USH2A mutations, longitudinal regression was used to estimate mean rates of change in Snellen visual acuity, Goldmann visual field area (V4e white test light), and 30-Hz (cone) full-field electroretinogram amplitude. These rates were compared with those of previously studied cohorts with dominant retinitis pigmentosa due to RHO mutations and with X-linked retinitis pigmentosa due to RPGR mutations. Rates of change in patients with the Cys759Phe mutation, the USH2A mutation associated with nonsyndromic disease, were compared with rates of change in patients with the Glu767fs mutation, the most common USH2A mutation associated with Usher syndrome type II (i.e., retinitis pigmentosa and hearing loss). Mean annual exponential rates of decline for the USH2A patients were 2.6% for visual acuity, 7.0% for visual field area, and 13.2% for electroretinogram amplitude. The rate of acuity loss fell between the corresponding rates for the RHO and RPGR patients, whereas the rates for field and ERG amplitude loss were faster than those for the RHO and RPGR patients. No significant differences were found for patients with the Cys759Phe mutation versus patients with the Glu767fs mutation. On average, USH2A patients lose visual acuity faster than RHO patients and slower than RPGR patients. USH2A patients lose visual field and cone electroretinogram amplitude faster than patients with RHO or RPGR mutations. Patients with a nonsyndromic USH2A mutation have the same retinal disease course as patients with syndromic USH2A disease.

  11. Genetics of recessive cognitive disorders.

    Science.gov (United States)

    Musante, Luciana; Ropers, H Hilger

    2014-01-01

    Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elucidation has lagged behind. Here we review recent progress in this field, show that ARID is not rare even in outbred Western populations, and discuss the prospects for improving its diagnosis and prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family.

    Science.gov (United States)

    Uzak, Asli Subasioglu; Tokgoz, Bulent; Dundar, Munis; Tekin, Mustafa

    2013-03-01

    Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the COL4A3 or COL4A4 genes, encoding type IV collagen. Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking COL4A3, COL4A4, and COL4A5 in 16 family members were typed. For mutation screening, all coding exons of COL4A3 were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA. The disease locus was mapped to chromosome 2q36.3, where COL4A3 and COL4A4 reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of COL4A3. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing. We present a large consanguineous Turkish family with AS that was found to have a COL4A3 mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis.

  13. Clinical Application of Screening for GJB2 Mutations before Cochlear Implantation in a Heterogeneous Population with High Rate of Autosomal Recessive Nonsyndromic Hearing Loss

    Directory of Open Access Journals (Sweden)

    Masoud Motasaddi Zarandy

    2011-01-01

    Full Text Available Clinical application of mutation screening and its effect on the outcome of cochlear implantation is widely debated. We investigated the effect of mutations in GJB2 gene on the outcome of cochlear implantation in a population with a high rate of consanguineous marriage and autosomal recessive nonsyndromic hearing loss. Two hundred and one children with profound prelingual sensorineural hearing loss were included. Forty-six patients had 35delG in GJB2. Speech awareness thresholds (SATs and speech recognition thresholds (SRTs improved following implantation, but there was no difference in performance between patients with GJB2-related deafness versus control (all >0.10. Both groups had produced their first comprehensible words within the same period of time following implantation (2.27 months in GJB2-related deaf versus 2.62 months in controls, =0.22. Although our findings demonstrate the need to uncover unidentified genetic causes of hereditary deafness, they do not support the current policy for genetic screening before cochlear implantation, nor prove a prognostic value.

  14. Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX Mutation in a Father and Son.

    Science.gov (United States)

    Arcot Sadagopan, Karthikeyan; Battista, Robert; Keep, Rosanne B; Capasso, Jenina E; Levin, Alex V

    2015-06-01

    Leber congenital amaurosis (LCA) is most often an autosomal recessive disorder. We report a father and son with autosomal dominant LCA due to a mutation in the CRX gene. DNA screening using an allele specific assay of 90 of the most common LCA-causing variations in the coding sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene was subsequently performed. Both father and son have a heterozygous single base pair deletion of an adenine at codon 153 in the coding sequence of the CRX gene resulting in a frameshift mutation. Mutations involving the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA.

  15. Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.

    Science.gov (United States)

    Zhang, Zhichun; Tian, Hua; Lv, Ping; Wang, Weiping; Jia, Zhuqing; Wang, Sainan; Zhou, Chunyan; Gao, Xuejun

    2015-01-01

    Mutation of distal-less homeobox 3 (DLX3) is responsible for human tricho-dento-osseous syndrome (TDO) with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP) genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO) inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

  16. Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome.

    Science.gov (United States)

    Rohena, Luis; Kuehn, Devon; Marchegiani, Shannon; Higginson, Jason D

    2011-04-01

    Ablepharon-macrostomia syndrome (AMS) is characterized by absent or short eyelids, macrostomia, ear anomalies, absent lanugo and hair, redundant skin, abnormal genitalia, and developmental delay in two-thirds of the reported patients. Additional anomalies include dry skin, growth retardation, hearing loss, camptodactyly, hypertelorism, absent zygomatic arches, and umbilical abnormalities. We present the second familial case of ablepharon-macrostomia syndrome in a newborn female and her 22-year-old father making autosomal dominant inheritance more likely than the previously proposed autosomal recessive transmission for this disorder. These cases likely represent the 16th and 17th reported cases of AMS and the first case suspected on prenatal ultrasound. Additionally, the child shows more prominent features of the disorder when compared to her father documenting variable expression and possible anticipation. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2011 Wiley-Liss, Inc.

  17. Homozygous SLC6A17 Mutations Cause Autosomal-Recessive Intellectual Disability with Progressive Tremor, Speech Impairment, and Behavioral Problems

    Science.gov (United States)

    Iqbal, Zafar; Willemsen, Marjolein H.; Papon, Marie-Amélie; Musante, Luciana; Benevento, Marco; Hu, Hao; Venselaar, Hanka; Wissink-Lindhout, Willemijn M.; Vulto-van Silfhout, Anneke T.; Vissers, Lisenka E.L.M.; de Brouwer, Arjan P.M.; Marouillat, Sylviane; Wienker, Thomas F.; Ropers, Hans Hilger; Kahrizi, Kimia; Nadif Kasri, Nael; Najmabadi, Hossein; Laumonnier, Frédéric; Kleefstra, Tjitske; van Bokhoven, Hans

    2015-01-01

    We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity mapping revealed homozygous mutations c.484G>A (p.Gly162Arg) and c.1898C>G (p.Pro633Arg) in SLC6A17. SLC6A17 is predominantly expressed in the brain, encodes a synaptic vesicular transporter of neutral amino acids and glutamate, and plays an important role in the regulation of glutamatergic synapses. Prediction programs and 3D modeling suggest that the identified mutations are deleterious to protein function. To directly test the functional consequences, we investigated the neuronal subcellular localization of overexpressed wild-type and mutant variants in mouse primary hippocampal neuronal cells. Wild-type protein was present in soma, axons, dendrites, and dendritic spines. p.Pro633Arg altered SLC6A17 was found in soma and proximal dendrites but did not reach spines. p.Gly162Arg altered SLC6A17 showed a normal subcellular distribution but was associated with an abnormal neuronal morphology mainly characterized by the loss of dendritic spines. In summary, our genetic findings implicate homozygous SLC6A17 mutations in autosomal-recessive intellectual disability, and their pathogenic role is strengthened by genetic evidence and in silico and in vitro functional analyses. PMID:25704603

  18. Single Nucleotide Polymorphisms of the GJB2 and GJB6 Genes Are Associated with Autosomal Recessive Nonsyndromic Hearing Loss

    Directory of Open Access Journals (Sweden)

    Ana Paula Grillo

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs are important markers in many studies that link DNA sequence variations to phenotypic changes; such studies are expected to advance the understanding of human physiology and elucidate the molecular basis of diseases. The DFNB1 locus, which contains the GJB2 and GJB6 genes, plays a key role in nonsyndromic hearing loss. Previous studies have identified important mutations in this locus, but the contribution of SNPs in the genes has not yet been much investigated. The aim of this study was to investigate the association of nine polymorphisms located within the DFNB1 locus with the occurrence of autosomal recessive nonsyndromic hearing loss (ARNSHL. The SNPs rs3751385 (C/T, rs7994748 (C/T, rs7329857 (C/T, rs7987302 (G/A, rs7322538 (G/A, rs9315400 (C/T, rs877098 (C/T, rs945369 (A/C, and rs7333214 (T/G were genotyped in 122 deaf patients and 132 healthy controls using allele-specific PCR. There were statistically significant differences between patients and controls, in terms of allelic frequencies in the SNPs rs3751385, rs7994748, rs7329857, rs7987302, rs945369, and rs7333214 (P<0.05. No significant differences between the two groups were observed for rs7322538, rs9315400, and rs877098. Our results suggest that SNPs present in the GJB2 and GJB6 genes may have an influence on ARNSHL in humans.

  19. The dynamics of DNA methylation and hydroxymethylation during amelogenesis.

    Science.gov (United States)

    Yoshioka, Hirotaka; Minamizaki, Tomoko; Yoshiko, Yuji

    2015-11-01

    Amelogenesis is a multistep process that relies on specific temporal and spatial signaling networks between the dental epithelium and mesenchymal tissues. Epigenetic modifications of key developmental genes in this process may be closely linked to a network of molecular events. However, the role of epigenetic regulation in amelogenesis remains unclear. Here, we have uncovered the spatial distributions of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) to determine epigenetic events in the mandibular incisors of mice. Immunohistochemistry and dot blotting showed that 5-hmC in ameloblasts increased from the secretory stage to the later maturation stage. We also demonstrated the distribution of 5-mC-positive ameloblasts with punctate nuclear labeling from sometime after the initiation of the secretory stage to the later maturation stage; however, dot blotting failed to detect this change. No obvious alteration of 5-mC/5-hmC staining in odontoblasts and dental pulp cells was observed. Concomitant with quantitative expression data, immunohistochemistry showed that maintenance DNA methyltransferase DNMT1 was highly expressed in immature dental epithelial cells and subsequently decreased at later stages of development. Meanwhile, de novo DNA methyltransferase Dnmt3a and Dnmt3b and DNA demethylase Tet family genes were universally expressed, except Tet1 that was highly expressed in immature dental epithelial cells. Thus, DNMT1 may sustain the undifferentiated status of dental epithelial cells through the maintenance of DNA methylation, while the hydroxylation of 5-mC may occur through the whole differentiation process by TET activity. Taken together, these data indicate that the dynamic changes of 5-mC and 5-hmC may be critical for the regulation of amelogenesis.

  20. Autosomal male determination in a spinosad-resistant housefly strain from Denmark

    DEFF Research Database (Denmark)

    Højland, Dorte H; Scott, Jeffrey G; Vagn Jensen, Karl-Martin

    2014-01-01

    males in this strain. The factor responsible for spinosad resistance in the strain is unknown, but previous studies suggest a role of cytochrome P450s for detoxification of spinosad. Sex determination in the housefly is controlled by a male-determining factor (M), either located on the Y chromosome......BACKGROUND The housefly, Musca domestica L., is a global pest and has developed resistance to most insecticides applied for its control. The insecticide spinosad plays an important role in housefly control. Females of the Danish housefly strain 791spin are threefold more resistant to spinosad than...... of resistance to spinosad. Sex determination in 791spin is due to a male factor on autosome 3. CONCLUSIONS The most likely explanation for the differentiation of spinosad resistance between males and females is a recessive spinosad resistance factor on autosome III. © 2013 Society of Chemical Industry...

  1. A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFbeta signaling and cause autosomal dominant spondylocarpotarsal synostosis

    NARCIS (Netherlands)

    Zieba, J.; Zhang, W.; Chong, J.X.; Forlenza, K.N.; Martin, J.H.; Heard, K.; Grange, D.K.; Butler, M.G.; Kleefstra, T.; Lachman, R.S.; Nickerson, D.; Regnier, M.; Cohn, D.H.; Bamshad, M.; Krakow, D.

    2017-01-01

    Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in

  2. Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.

    Directory of Open Access Journals (Sweden)

    Zhichun Zhang

    Full Text Available Mutation of distal-less homeobox 3 (DLX3 is responsible for human tricho-dento-osseous syndrome (TDO with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

  3. Implementing Non-Invasive Prenatal Diagnosis (NIPD) in a National Health Service Laboratory; From Dominant to Recessive Disorders.

    Science.gov (United States)

    Drury, Suzanne; Mason, Sarah; McKay, Fiona; Lo, Kitty; Boustred, Christopher; Jenkins, Lucy; Chitty, Lyn S

    2016-01-01

    Our UK National Health Service regional genetics laboratory offers NIPD for autosomal dominant and de novo conditions (achondroplasia, thanataphoric dysplasia, Apert syndrome), paternal mutation exclusion for cystic fibrosis and a range of bespoke tests. NIPD avoids the risks associated with invasive testing, making prenatal diagnosis more accessible to families at high genetic risk. However, the challenge remains in offering definitive diagnosis for autosomal recessive diseases, which is complicated by the predominance of the maternal mutant allele in the cell-free DNA sample and thus requires a variety of different approaches. Validation and diagnostic implementation for NIPD of congenital adrenal hyperplasia (CAH) is further complicated by presence of a pseudogene that requires a different approach. We have used an assay targeting approximately 6700 heterozygous SNPs around the CAH gene (CYP21A2) to construct the high-risk parental haplotypes and tested this approach in five cases, showing that inheritance of the parental alleles can be correctly identified using NIPD. We are evaluating various measures of the fetal fraction to help determine inheritance of parental mutations. We are currently exploring the utility of an NIPD multi-disorder panel for autosomal recessive disease, to make testing more widely applicable to families with a variety of serious genetic conditions.

  4. Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8

    Science.gov (United States)

    Boycott, Kym M.; Beaulieu, Chandree L.; Kernohan, Kristin D.; Gebril, Ola H.; Mhanni, Aziz; Chudley, Albert E.; Redl, David; Qin, Wen; Hampson, Sarah; Küry, Sébastien; Tetreault, Martine; Puffenberger, Erik G.; Scott, James N.; Bezieau, Stéphane; Reis, André; Uebe, Steffen; Schumacher, Johannes; Hegele, Robert A.; McLeod, D. Ross; Gálvez-Peralta, Marina; Majewski, Jacek; Ramaekers, Vincent T.; Nebert, Daniel W.; Innes, A. Micheil; Parboosingh, Jillian S.; Abou Jamra, Rami

    2015-01-01

    Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development. PMID:26637978

  5. Autosomal-recessive and X-linked forms of hereditary motor and sensory neuropathy in childhood.

    Science.gov (United States)

    Ouvrier, Robert; Geevasingha, Nimeshan; Ryan, Monique M

    2007-08-01

    The hereditary motor and sensory neuropathies (HMSNs, Charcot-Marie-Tooth neuropathies) are the most common degenerative disorders of the peripheral nervous system. In recent years a dramatic expansion has occurred in our understanding of the molecular basis and cell biology of the recessively inherited demyelinating and axonal neuropathies, with delineation of a number of new neuropathies. Mutations in some genes cause a wide variety of clinical, neurophysiologic, and pathologic phenotypes, rendering diagnosis difficult. The X-linked forms of HMSN represent at least 10%-15% of all HMSNs and have an expanded disease spectrum including demyelinating, intermediate, and axonal neuropathies, transient central nervous system (CNS) dysfunction, mental retardation, and hearing loss. This review presents an overview of the recessive and X-linked forms of HMSN observed in childhood, with particular reference to disease phenotype and neurophysiologic and pathologic abnormalities suggestive of specific diagnoses. These findings can be used by the clinician to formulate a differential diagnosis and guide targeted genetic testing.

  6. A novel approach identifying hybrid sterility QTL on the autosomes of Drosophila simulans and D. mauritiana.

    Science.gov (United States)

    Dickman, Christopher T D; Moehring, Amanda J

    2013-01-01

    When species interbreed, the hybrid offspring that are produced are often sterile. If only one hybrid sex is sterile, it is almost always the heterogametic (XY or ZW) sex. Taking this trend into account, the predominant model used to explain the genetic basis of F1 sterility involves a deleterious interaction between recessive sex-linked loci from one species and dominant autosomal loci from the other species. This model is difficult to evaluate, however, as only a handful of loci influencing interspecies hybrid sterility have been identified, and their autosomal genetic interactors have remained elusive. One hindrance to their identification has been the overwhelming effect of the sex chromosome in mapping studies, which could 'mask' the ability to accurately map autosomal factors. Here, we use a novel approach employing attached-X chromosomes to create reciprocal backcross interspecies hybrid males that have a non-recombinant sex chromosome and recombinant autosomes. The heritable variation in phenotype is thus solely caused by differences in the autosomes, thereby allowing us to accurately identify the number and location of autosomal sterility loci. In one direction of backcross, all males were sterile, indicating that sterility could be entirely induced by the sex chromosome complement in these males. In the other direction, we identified nine quantitative trait loci that account for a surprisingly large amount (56%) of the autosome-induced phenotypic variance in sterility, with a large contribution of autosome-autosome epistatic interactions. These loci are capable of acting dominantly, and thus could contribute to F1 hybrid sterility.

  7. A novel approach identifying hybrid sterility QTL on the autosomes of Drosophila simulans and D. mauritiana.

    Directory of Open Access Journals (Sweden)

    Christopher T D Dickman

    Full Text Available When species interbreed, the hybrid offspring that are produced are often sterile. If only one hybrid sex is sterile, it is almost always the heterogametic (XY or ZW sex. Taking this trend into account, the predominant model used to explain the genetic basis of F1 sterility involves a deleterious interaction between recessive sex-linked loci from one species and dominant autosomal loci from the other species. This model is difficult to evaluate, however, as only a handful of loci influencing interspecies hybrid sterility have been identified, and their autosomal genetic interactors have remained elusive. One hindrance to their identification has been the overwhelming effect of the sex chromosome in mapping studies, which could 'mask' the ability to accurately map autosomal factors. Here, we use a novel approach employing attached-X chromosomes to create reciprocal backcross interspecies hybrid males that have a non-recombinant sex chromosome and recombinant autosomes. The heritable variation in phenotype is thus solely caused by differences in the autosomes, thereby allowing us to accurately identify the number and location of autosomal sterility loci. In one direction of backcross, all males were sterile, indicating that sterility could be entirely induced by the sex chromosome complement in these males. In the other direction, we identified nine quantitative trait loci that account for a surprisingly large amount (56% of the autosome-induced phenotypic variance in sterility, with a large contribution of autosome-autosome epistatic interactions. These loci are capable of acting dominantly, and thus could contribute to F1 hybrid sterility.

  8. Autosomal dominant epidermodysplasia verruciformis lacking a known EVER1 or EVER2 mutation

    OpenAIRE

    McDermott, David H.; Gammon, Bryan; Snijders, Peter J.; Mbata, Ihunanya; Phifer, Beth; Hartley, A. Howland; Lee, Chyi-Chia Richard; Murphy, Philip M.; Hwang, Sam T.

    2009-01-01

    Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to infection with specific human papillomavirus (HPV) serotypes. EV is a genetically heterogeneous disease, and autosomal recessive and X-linked inheritance patterns have been reported. Nonsense mutations in the genes EVER1 and EVER2 have been identified in over 75% of cases. We present EV in a father and son with typical histologic and clinical findings that occur in the absence of mutation...

  9. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation

    DEFF Research Database (Denmark)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian Gryesten

    2011-01-01

    Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation......Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation...

  10. Digenic inheritance in autosomal recessive non-syndromic hearing loss cases carrying GJB2 heterozygote mutations: assessment of GJB4, GJA1, and GJC3.

    Science.gov (United States)

    Kooshavar, Daniz; Tabatabaiefar, Mohammad Amin; Farrokhi, Effat; Abolhasani, Marziye; Noori-Daloii, Mohammad-Reza; Hashemzadeh-Chaleshtori, Morteza

    2013-02-01

    Autosomal recessive non-syndromic hearing loss (ARNSHL) can be caused by many genes. However, mutations in the GJB2 gene, which encodes the gap-junction (GJ) protein connexin (Cx) 26, constitute a considerable proportion differing among population. Between 10 and 42 percent of patients with recessive GJB2 mutations carry only one mutant allele. Mutations in GJB4, GJA1, and GJC3 encoding Cx30.3, Cx43, and Cx29, respectively, can lead to HL. Combination of different connexins in heteromeric and heterotypic GJ assemblies is possible. This study aims to determine whether variations in any of the genes GJB4, GJA1 or GJC3 can be the second mutant allele causing the disease in the digenic mode of inheritance in the studied GJB2 heterozygous cases. We examined 34 unrelated GJB2 heterozygous ARNSHL subjects from different geographic and ethnic areas in Iran, using polymerase chain reaction (PCR) followed by direct DNA sequencing to identify any sequence variations in these genes. Restriction fragment length polymorphism (RFLP) assays were performed on 400 normal hearing individuals. Sequence analysis of GJB4 showed five heterozygous variations including c.451C>A, c.219C>T, c.507C>G, c.155_158delTCTG and c.542C>T, with only the latter variation not being detected in any of control samples. There were three heterozygous variations including c.758C>T, c.717G>A and c.3*dupA in GJA1 in four cases. We found no variations in GJC3 gene sequence. Our data suggest that GJB4 c.542C>T variant and less likely some variations of GJB4 and GJA1, but not possibly GJC3, can be assigned to ARNSHL in GJB2 heterozygous mutation carriers providing clues of the digenic pattern. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

    Science.gov (United States)

    Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

    2016-12-01

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis. © International & American Associations for Dental Research 2016.

  12. Homozygous SLC6A17 mutations cause autosomal-recessive intellectual disability with progressive tremor, speech impairment, and behavioral problems.

    Science.gov (United States)

    Iqbal, Zafar; Willemsen, Marjolein H; Papon, Marie-Amélie; Musante, Luciana; Benevento, Marco; Hu, Hao; Venselaar, Hanka; Wissink-Lindhout, Willemijn M; Vulto-van Silfhout, Anneke T; Vissers, Lisenka E L M; de Brouwer, Arjan P M; Marouillat, Sylviane; Wienker, Thomas F; Ropers, Hans Hilger; Kahrizi, Kimia; Nadif Kasri, Nael; Najmabadi, Hossein; Laumonnier, Frédéric; Kleefstra, Tjitske; van Bokhoven, Hans

    2015-03-05

    We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity mapping revealed homozygous mutations c.484G>A (p.Gly162Arg) and c.1898C>G (p.Pro633Arg) in SLC6A17. SLC6A17 is predominantly expressed in the brain, encodes a synaptic vesicular transporter of neutral amino acids and glutamate, and plays an important role in the regulation of glutamatergic synapses. Prediction programs and 3D modeling suggest that the identified mutations are deleterious to protein function. To directly test the functional consequences, we investigated the neuronal subcellular localization of overexpressed wild-type and mutant variants in mouse primary hippocampal neuronal cells. Wild-type protein was present in soma, axons, dendrites, and dendritic spines. p.Pro633Arg altered SLC6A17 was found in soma and proximal dendrites but did not reach spines. p.Gly162Arg altered SLC6A17 showed a normal subcellular distribution but was associated with an abnormal neuronal morphology mainly characterized by the loss of dendritic spines. In summary, our genetic findings implicate homozygous SLC6A17 mutations in autosomal-recessive intellectual disability, and their pathogenic role is strengthened by genetic evidence and in silico and in vitro functional analyses. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. Calpain 12 Function Revealed through the Study of an Atypical Case of Autosomal Recessive Congenital Ichthyosis.

    Science.gov (United States)

    Bochner, Ron; Samuelov, Liat; Sarig, Ofer; Li, Qiaoli; Adase, Christopher A; Isakov, Ofer; Malchin, Natalia; Vodo, Dan; Shayevitch, Ronna; Peled, Alon; Yu, Benjamin D; Fainberg, Gilad; Warshauer, Emily; Adir, Noam; Erez, Noam; Gat, Andrea; Gottlieb, Yehonatan; Rogers, Tova; Pavlovsky, Mor; Goldberg, Ilan; Shomron, Noam; Sandilands, Aileen; Campbell, Linda E; MacCallum, Stephanie; McLean, W H Irwin; Ast, Gil; Gallo, Richard L; Uitto, Jouni; Sprecher, Eli

    2017-02-01

    Congenital erythroderma is a rare and often life-threatening condition, which has been shown to result from mutations in several genes encoding important components of the epidermal differentiation program. Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with two forms of ichthyosis, autosomal recessive congenital ichthyosis, and harlequin ichthyosis. Because the patient displayed an atypical phenotype, including severe hair and nail manifestations, we scrutinized the exome sequencing data for additional potentially deleterious genetic variations in genes of relevance to the cornification process. Two mutations were identified in CAPN12, encoding a member of the calpain proteases: a paternal missense mutation (c.1511C>A; p.P504Q) and a maternal deletion due to activation of a cryptic splice site in exon 9 of the gene (c.1090_1129del; p.Val364Lysfs*11). The calpain 12 protein was found to be expressed in both the epidermis and hair follicle of normal skin, but its expression was dramatically reduced in the patient's skin. The downregulation of capn12 expression in zebrafish was associated with abnormal epidermal morphogenesis. Small interfering RNA knockdown of CAPN12 in three-dimensional human skin models was associated with acanthosis, disorganized epidermal architecture, and downregulation of several differentiation markers, including filaggrin. Accordingly, filaggrin expression was almost absent in the patient skin. Using ex vivo live imaging, small interfering RNA knockdown of calpain 12 in skin from K14-H2B GFP mice led to significant hair follicle catagen transformation compared with controls. In summary, our results indicate that calpain 12 plays an essential role during epidermal ontogenesis and normal hair follicle cycling and that

  14. Stable Isotopes Reveal Rapid Enamel Elongation (Amelogenesis) Rates for the Early Cretaceous Iguanodontian Dinosaur Lanzhousaurus magnidens.

    Science.gov (United States)

    Suarez, Celina A; You, Hai-Lu; Suarez, Marina B; Li, Da-Qing; Trieschmann, J B

    2017-11-10

    Lanzhousaurus magnidens, a large non-hadrosauriform iguanodontian dinosaur from the Lower Cretaceous Hekou Group of Gansu Province, China has the largest known herbivorous dinosaur teeth. Unlike its hadrosauriform relatives possessing tooth batteries of many small teeth, Lanzhousaurus utilized a small number (14) of very large teeth (~10 cm long) to create a large, continuous surface for mastication. Here we investigate the significance of Lanzhousaurus in the evolutionary history of iguanodontian-hadrosauriform transition by using a combination of stable isotope analysis and CT imagery. We infer that Lanzhousaurus had a rapid rate of tooth enamel elongation or amelogenesis at 0.24 mm/day with dental tissues common to other Iguanodontian dinosaurs. Among ornithopods, high rates of amelogenesis have been previously observed in hadrosaurids, where they have been associated with a sophisticated masticatory apparatus. These data suggest rapid amelogenesis evolved among non-hadrosauriform iguanodontians such as Lanzhousaurus, representing a crucial step that was exapted for the evolution of the hadrosaurian feeding mechanism.

  15. GEP, a local growth factor, is critical for odontogenesis and amelogenesis.

    Science.gov (United States)

    Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q

    2010-11-25

    Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development.

  16. A Comparison of Selective Pressures in Plant X-Linked and Autosomal Genes.

    Science.gov (United States)

    Krasovec, Marc; Nevado, Bruno; Filatov, Dmitry A

    2018-05-03

    Selection is expected to work differently in autosomal and X-linked genes because of their ploidy difference and the exposure of recessive X-linked mutations to haploid selection in males. However, it is not clear whether these expectations apply to recently evolved sex chromosomes, where many genes retain functional X- and Y-linked gametologs. We took advantage of the recently evolved sex chromosomes in the plant Silene latifolia and its closely related species to compare the selective pressures between hemizygous and non-hemizygous X-linked genes as well as between X-linked genes and autosomal genes. Our analysis, based on over 1000 genes, demonstrated that, similar to animals, X-linked genes in Silene evolve significantly faster than autosomal genes—the so-called faster-X effect. Contrary to expectations, faster-X divergence was detectable only for non-hemizygous X-linked genes. Our phylogeny-based analyses of selection revealed no evidence for faster adaptation in X-linked genes compared to autosomal genes. On the other hand, partial relaxation of purifying selection was apparent on the X-chromosome compared to the autosomes, consistent with a smaller genetic diversity in S. latifolia X-linked genes (π x = 0.016; π aut = 0.023). Thus, the faster-X divergence in S. latifolia appears to be a consequence of the smaller effective population size rather than of a faster adaptive evolution on the X-chromosome. We argue that this may be a general feature of “young” sex chromosomes, where the majority of X-linked genes are not hemizygous, preventing haploid selection in heterogametic sex.

  17. Ceramic Veneers and Direct-Composite Cases of Amelogenesis Imperfecta Rehabilitation.

    Science.gov (United States)

    Shibata, S; Taguchi, Cmc; Gondo, R; Stolf, S C; Baratieri, L N

    2016-01-01

    The aim of this article is to present two case reports for the treatment of patients affected with amelogenesis imperfecta. One case was treated with composite resin and the other case with ceramic veneers. Esthetic and functional results were achieved using both treatments, and a review of advantages and disadvantages is presented.

  18. Autosomal recessive polycystic kidney disorder due to two novel compound heterozygote mutations in PKHD1 gene: case report

    Directory of Open Access Journals (Sweden)

    Mohammad Miryounesi

    2017-01-01

    Full Text Available Background: Autosomal recessive polycystic kidney disorder (ARPCKD is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC. It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys. Case presentation: Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A. Bioinformatics tools predicted these variants to be pathogenic. Conclusion: In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder.

  19. Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.

    NARCIS (Netherlands)

    Avila-Fernandez, A.; Cantalapiedra, D.; Aller, E.; Vallespin, E.; Aguirre-Lamban, J.; Blanco-Kelly, F.; Corton, M.; Riveiro-Alvarez, R.; Allikmets, R.; Trujillo-Tiebas, M.J.; Millan, J.M.; Cremers, F.P.M.; Ayuso, C.

    2010-01-01

    PURPOSE: Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations in 272 Spanish families using a genotyping microarray. METHODS: 272 unrelated Spanish families, 107 with autosomal

  20. The overview of channels, transporters, and calcium signaling molecules during amelogenesis.

    Science.gov (United States)

    Kim, Hee-Eun; Hong, Jeong Hee

    2018-05-20

    Enamel is a highly calcified tissue. Its formation requires a progressive and dynamic system for the regulation of electrolyte concentration by enamel epithelia. A critical function of enamel epithelial cells, ameloblasts, is the secretion and movement of electrolytes via various channels and transporters to develop the enamel tissue. Enamel formation generates protons, which need to be neutralised. Thus, ameloblasts possess a buffering system to sustain mineral accretion. Normal tooth formation involves stage-dependent net fluctuations in pH during amelogenesis. To date, all of our information about ion transporters in dental enamel tissue is based solely on immunostaining-expression techniques. This review critically evaluates the current understanding and recent discoveries and physiological role of ion channels and transporters, Mg 2+ transporters, and Ca 2+ regulatory proteins during amelogenesis in enamel formation. The ways in which ameloblasts modulate ions are discussed in the context of current research for developing a novel morphologic-functional model of enamel maturation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Literature review of amelogenesis imperfecta with case report

    Directory of Open Access Journals (Sweden)

    Sumathy C Chanmougananda

    2012-01-01

    Full Text Available Amelogenesis impertecta (Al is a diverse collection of inherited diseases that exhibit qualitative or quantitative tooth enamel defects in the absence of systemic manifestations. Also known by varied names, such as hereditary enamel dysplasia, hereditary brown opalescent teeth, this defect is entirely ectodermal, since mesodermal components of the teeth are basically normal. This article details a case of Al along with complete review which presents in his twin siblings with clinical, radiological and histopathological report.

  2. Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

    Directory of Open Access Journals (Sweden)

    Ana Cotta

    2014-09-01

    Full Text Available Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.

  3. Assessing the putative roles of X-autosome and X-Y interactions in hybrid male sterility of the Drosophila bipectinata species complex.

    Science.gov (United States)

    Mishra, Paras Kumar; Singh, Bashisth Narayan

    2007-07-01

    Interspecific F1 hybrid males of the Drosophila bipectinata species complex are sterile, while females are fertile, following Haldane's rule. A backcross scheme involving a single recessive visible marker on the X chromosome has been used to assess the putative roles of X-autosome and X-Y interactions in hybrid male sterility in the D. bipectinata species complex. The results suggest that X-Y interactions are playing the major role in hybrid male sterility in the crosses D. bipectinata x D. parabipectinata and D. bipectinata x D. pseudoananassae, while X-autosome interactions are largely involved in hybrid male sterility in the crosses D. malerkotliana x D. bipectinata and D. malerkotliana x D. parabipectinata. However, by using this single marker it is not possible to rule out the involvement of autosome-autosome interactions in hybrid male sterility. These findings also lend further support to the phylogenetic relationships among 4 species of the D. bipectinata complex.

  4. Gene therapy in animal models of autosomal dominant retinitis pigmentosa

    Science.gov (United States)

    Rossmiller, Brian; Mao, Haoyu

    2012-01-01

    Gene therapy for dominantly inherited genetic disease is more difficult than gene-based therapy for recessive disorders, which can be treated with gene supplementation. Treatment of dominant disease may require gene supplementation partnered with suppression of the expression of the mutant gene either at the DNA level, by gene repair, or at the RNA level by RNA interference or transcriptional repression. In this review, we examine some of the gene delivery approaches used to treat animal models of autosomal dominant retinitis pigmentosa, focusing on those models associated with mutations in the gene for rhodopsin. We conclude that combinatorial approaches have the greatest promise for success. PMID:23077406

  5. Cleft lip with or without cleft palate in Shanghai, China: Evidence for an autosomal major locus

    Energy Technology Data Exchange (ETDEWEB)

    Marazita, M.L. (Virginia Commonwealth Univ., Richmond, VA (United States)); Hu, Dan-Ning; Liu, You-E. (Zhabei Eye Institute, Shanghai (China)); Spence, A. (Univ. of California, Los Angeles, CA (United States)); Melnick, M. (Univ. of Southern California, Los Angeles, CA (United States))

    1992-09-01

    Orientals are at higher risk for cleft lip with our without cleft palate (CL[+-] P) than Caucasians or blacks. The authors collected demographic and family data to study factors contributing to the etiology of CL[+-]P in Shanghai. The birth incidence of nonsyndromic CL[+-]P (SHanghai 1980-87) was 1.11/1,000, with a male/female ratio of 1.42. Almost 2,000 nonsyndromic CL[+-]P probands were ascertained from individuals operated on during the years 1956-83 at surgical hospitals in Shanghai. Detailed family histories and medical examinations were obtained for the probands and all available family members. Genetic analysis of the probands' families were performed under the mixed model with major locus (ML) and multifactorial (MFT) components. The hypothesis of no familial transmission and of MFT alone could be rejected. Of the ML models, the autosomal recessive was significantly most likely and was assumed for testing three complex hypothesis: (1) ML and sporadics; (2) ML and MFT; (3) ML, MFT, and sporadics. None of the complex models were more likely than the ML alone model. In conclusion, the best-fitting, most parsimonious model for CL[+-]P in Shanghai was that of an autosomal recessive major locus. 37 refs., 1 tab.

  6. Assessment of restorative treatment of patients with amelogenesis imperfecta.

    Science.gov (United States)

    Chen, Chiung-Fen; Hu, Jan Ching Chun; Estrella, Maria Regina Padilla; Peters, Mathilde C; Bresciani, Eduardo

    2013-01-01

    The purpose of this study was to assess restorative treatment outcomes in the mixed dentition of amelogenesis imperfecta (AI) patients and determine the postrehabilitation oral health status and satisfaction of the patients. Clinical and radiographic examinations were performed on eight AI patients, who had 74 restorations placed in permanent incisors and molars, to allow evaluation of the integrity of the restorations and periodontal status post-treatment. Subjects completed a survey regarding esthetics, function, and sensitivity. Among the 74 restorations evaluated, seven were lost; of the remaining restorations, 31 were posterior, and 36 were anterior. Ten were rated clinically unacceptable. Teeth with stainless steel crowns had a moderate gingival index (mean=2.3) and plaque index (mean=2.0) scores. Widening of the periodontal ligament and pulp canal obliteration were common radiographic findings. Subject's recall of satisfaction regarding esthetics (P=.002) and sensitivity (brushing-P=.03; eating-P=.01) showed a statically significant difference before and after treatment. During mixed dentition, teeth with amelogenesis imperfecta may be restored with conventional treatment modalities. Direct restorations should be considered "interim" with multiple repairs anticipated. Post-treatment, gingival inflammation and plaque accumulation were observed. Subjects were satisfied with their appearance and reported a decrease of hypersensitivity.

  7. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies

    Directory of Open Access Journals (Sweden)

    Steven J. Brookes

    2017-09-01

    Full Text Available During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other “professional” secretory cells, ameloblasts employ the unfolded protein response (UPR to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  8. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Dixon, Michael J; Kirkham, Jennifer

    2017-01-01

    During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other "professional" secretory cells, ameloblasts employ the unfolded protein response (UPR) to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum)/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI) and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  9. Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.

    Science.gov (United States)

    Hackl, Agnes; Mehler, Katrin; Gottschalk, Ingo; Vierzig, Anne; Eydam, Marcus; Hauke, Jan; Beck, Bodo B; Liebau, Max C; Ensenauer, Regina; Weber, Lutz T; Habbig, Sandra

    2017-05-01

    Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early

  10. A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Xiong, Huaqi; Chen, Yongxiong; Yi, Yajun; Tsuchiya, Karen; Moeckel, Gilbert; Cheung, Joseph; Liang, Dan; Tham, Kyi; Xu, Xiaohu; Chen, Xing-Zhen; Pei, York; Zhao, Zhizhuang Jeo; Wu, Guanqing

    2002-07-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a common hereditary renal cystic disease in infants and children. By genetic linkage analyses, the gene responsible for this disease, termed polycystic kidney and hepatic disease 1 (PKHD1), was mapped on human chromosome 6p21.1-p12, and has been further localized to a 1-cM genetic interval flanked by the D6S1714/D6S243 (telomeric) and D6S1024 (centromeric) markers. We recently identified a novel gene in this genetic interval from kidney cDNA, using cloning strategies. The gene PKHD1 (PKHD1-tentative) encodes a novel 3396-amino-acid protein with no apparent homology with any known proteins. We named its gene product "tigmin" because it contains multiple TIG domains, which usually are seen in proteins containing immunoglobulin-like folds. PKHD1 encodes an 11.6-kb transcript and is composed of 61 exons spanning an approximately 365-kb genomic region on chromosome 6p12-p11.2 adjacent to the marker D6S1714. Northern blot analyses demonstrated that the gene has discrete bands with one peak signal at approximately 11 kb, indicating that PKHD1 is likely to have multiple alternative transcripts. PKHD1 is highly expressed in adult and infant kidneys and weakly expressed in liver in northern blot analysis. This expression pattern parallels the tissue involvement observed in ARPKD. In situ hybridization analysis further revealed that the expression of PKHD1 in the kidney is mainly localized to the epithelial cells of the collecting duct, the specific tubular segment involved in cyst formation in ARPKD. These features of PKHD1 make it a strong positional candidate gene for ARPKD.

  11. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Directory of Open Access Journals (Sweden)

    Cali E Willet

    Full Text Available Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant. Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  12. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Science.gov (United States)

    Willet, Cali E; Makara, Mariano; Reppas, George; Tsoukalas, George; Malik, Richard; Haase, Bianca; Wade, Claire M

    2015-01-01

    Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant). Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  13. Recurrent De Novo Mutations Affecting Residue Arg1 38 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa

    NARCIS (Netherlands)

    Fischer-Zirnsak, Björn; Escande-Beillard, Nathalie; Ganesh, Jaya; Tan, Yu Xuan; Al Bughaili, Mohammed; Lin, Angela E.; Sahai, Inderneel; Bahena, Paulina; Reichert, Sara L.; Loh, Abigail; Wright, Graham D.; Liu, Jaron; Rahikkala, Elisa; Pivnick, Eniko K.; Choudhri, Asim F.; Krüger, Ulrike; Zemojtel, Tomasz; van Ravenswaaij-Arts, Conny; Mostafavi, Roya; Stolte-Dijkstra, Irene; Symoens, Sofie; Pajunen, Leila; Al-Gazali, Lihadh; Meierhofer, David; Robinson, Peter N.; Mundlos, Stefan; Villarroel, Camilo E.; Byers, Peter; Masri, Amira; Robertson, Stephen P.; Schwarze, Ulrike; Callewaert, Bert; Reversade, Bruno; Kornak, Uwe

    2015-01-01

    Progeroid disorders overlapping with De Barsy syndrome (DBS) are collectively denoted as autosomal-recessive cutis laxa type 3 (ARCL3). They are caused by biallelic mutations in PYCR1 or ALDH18A1, encoding pyrroline-5-carboxylate reductase 1 and pyrroline-5-carboxylate synthase (P5CS), respectively,

  14. Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis.

    Science.gov (United States)

    Jedeon, Katia; Loiodice, Sophia; Salhi, Khaled; Le Normand, Manon; Houari, Sophia; Chaloyard, Jessica; Berdal, Ariane; Babajko, Sylvie

    2016-11-01

    Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality.

  15. An autosomal recessive leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa maps to chromosome 17q24.2-25.3

    Directory of Open Access Journals (Sweden)

    Bouhouche Ahmed

    2012-03-01

    Full Text Available Abstract Background Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. To identify new genes responsible of such diseases, we studied a consanguineous Moroccan family with three affected individuals displaying hereditary leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa that appears to segregate in autosomal recessive pattern. Methods All family members underwent neurological and radiological examinations. A genome wide search was conducted in this family using the ABI PRISM linkage mapping set version 2.5 from Applied Biosystems. Six candidate genes within the region linked to the disease were screened for mutations by direct sequencing. Results Evidence of linkage was obtained on chromosome 17q24.2-25.3. Analysis of recombination events and LOD score calculation suggests linkage of the responsible gene in a genetic interval of 11 Mb located between D17S789 and D17S1806 with a maximal multipoint LOD score of 2.90. Sequencing of seven candidate genes in this locus, ATP5H, FDXR, SLC25A19, MCT8, CYGB, KCNJ16 and GRIN2C, identified three missense mutations in the FDXR gene which were also found in a homozygous state in three healthy controls, suggesting that these variants are not disease-causing mutations in the family. Conclusion A novel locus for leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa has been mapped to chromosome 17q24.2-25.3 in a consanguineous Moroccan family.

  16. Correction of malocclusion and oral rehabilitation in a case of amelogenesis imperfecta by insertion of dental implants followed by Le Fort I distraction osteogenesis of the edentulous atrophic maxilla

    OpenAIRE

    Apaydin, Aysegul; Sermet, Bulent; Ureturk, Sevin; Kundakcioglu, Abdulsamet

    2014-01-01

    Background Amelogenesis imperfecta refers a group of hereditary diseases affecting the teeth and can present a variety of clinical forms and appearances, compromising esthetic appearance. Amelogenesis imperfecta variably reduces oral health quality and can result in severe psychological problems. Case presentation We present the management of an amelogenesis imperfecta Angle class III malocclusion case with speech, esthetics and functional problems. This is an example of the rarely presented ...

  17. New evidence for the role of calpain 10 in autosomal recessive intellectual disability: identification of two novel nonsense variants by exome sequencing in Iranian families.

    Science.gov (United States)

    Oladnabi, Morteza; Musante, Luciana; Larti, Farzaneh; Hu, Hao; Abedini, Seyedeh Sedigheh; Wienker, Thomas; Ropers, Hans Hilger; Kahrizi, Kimia; Najmabadi, Hossein

    2015-03-01

    Knowledge of the genes responsible for intellectual disability, particularly autosomal recessive forms, is rapidly expanding. Increasing numbers of the gene show great heterogeneity and supports the hypothesis that human genome may contain over 2000 causative genes with a critical role in brain development. Since 2004, we have applied genome-wide SNP genotyping and next-generation sequencing in large consanguineous Iranian families with intellectual disability, to identify the genes harboring disease-causing mutations. The current study paved the way for identification of responsible genes in two unrelated Iranian families. We found two novel nonsense mutations, p.C77* and p.Q115*, in the calpain catalytic domain of CAPN10, which is a cysteine protease known to be involved in pathogenesis of noninsulin-dependent diabetes mellitus. Another different mutation in this gene (p.S138_R139ins5) has previously been reported in an Iranian family. All of these patients have common clinical features in spite of specific brain structural abnormalities on MRI. Different mutations in CAPN10 have already been found in three independent Iranian families. These results have strongly supported the possible role of CAPN10 in human brain development. Altogether, we proposed CAPN10 as a promising candidate gene for intellectual disability, which should be considered in diagnostic gene panels.

  18. Oral Rehabilitation of Young Adult with Amelogenesis Imperfecta.

    Science.gov (United States)

    Leung, Vincent Ws; Low, Bernard; Yang, Yanqi; Botelho, Michael G

    2018-05-01

    Amelogenesis imperfecta is a heterogeneous group of hereditary disorders that affect the enamel formation of the primary and permanent dentitions while the remaining tooth structure is normal. Appropriate patient care is necessary to prevent adverse effects on dental oral health, dental disfigurement, and psychological well-being. This clinical report presents a 27-year-old Chinese male with amelogenesis imperfecta (AI) and his restorative management. This clinical report presents a 27-year-old Chinese male with AI and his restorative management. Extraoral examination showed a skeletal class III profile and increased lower facial proportion. Intraorally, all the permanent dentition was hypoplastic with noticeable tooth surface loss and a yellow-brown appearance. This was complicated with a mild maloc-clusion and food packing on his posterior teeth. The patient wanted to improve his appearance and masticatory efficiency. Orthodontic treatment was performed to treat the mild malocclu-sion and create physiological interproximal spacing to minimize tooth preparation and facilitate oral hygiene. This report demonstrates how a multidisciplinary approach for the management of AI can achieve a predictable, functional, and esthetic outcome. Orthodontic treatment facilitated a conservative prosthodontic treatment outcome by selectively increasing interproximal space, minimizing tooth preparation, correcting posterior bilateral cross-bite, as well as an anterior reverse overjet and derotation of the canines. This case report demonstrates the effective restoration of AI using a multidisciplinary approach to overcome crowding using a relatively conservative approach.

  19. Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome

    OpenAIRE

    De Vos, Michel; Hayward, Bruce E.; Picton, Susan; Sheridan, Eamonn; Bonthron, David T.

    2004-01-01

    We investigated a family with an autosomal recessive syndrome of café-au-lait patches and childhood malignancy, notably supratentorial primitive neuroectodermal tumor. There was no cancer predisposition in heterozygotes; nor was there bowel cancer in any individual. However, autozygosity mapping indicated linkage to a region of 7p22 surrounding the PMS2 mismatch-repair gene. Sequencing of genomic PCR products initially failed to identify a PMS2 mutation. Genome searches then revealed a previo...

  20. Functional and esthetic rehabilitation of a child with amelogenesis imperfecta: a case report.

    Science.gov (United States)

    Moura, Carmem Dolores Vilarinho Soares de; Pontes, Alessandra Silva; Lopes, Teresinha Soares Pereira; Moura, Lúcia Fátima Almeida de Deus; Lima, Marina Deus Moura de

    2017-01-01

    Amelogenesis imperfecta (AI) is a tooth disorder characterized by the abnormal development of the enamel in response to mutations in the genes involved in amelogenesis. The objective of this article is to present the clinical case of a child with AI in the primary dentition phase. A 4-year-old boy was presented to a clinic by his mother, who complained that her son's smile esthetics were compromised by "weak and yellow teeth." All the teeth showed yellowish discoloration as well as crumbling or missing enamel. Due to the absence of carious lesions and the presence of normal pulp in the teeth, it was decided to restore the dentition with indirect crowns of ceramic-optimized polymer, also known as ceromer. No preparations were performed on the teeth. For this patient, indirect ceromer restorations presented a good treatment option for the rehabilitation of primary teeth affected by AI.

  1. [Clinical and molecular study in a family with autosomal dominant hypohidrotic ectodermal dysplasia].

    Science.gov (United States)

    Callea, Michele; Cammarata-Scalisi, Francisco; Willoughby, Colin E; Giglio, Sabrina R; Sani, Ilaria; Bargiacchi, Sara; Traficante, Giovanna; Bellacchio, Emanuele; Tadini, Gianluca; Yavuz, Izzet; Galeotti, Angela; Clarich, Gabriella

    2017-02-01

    Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by deficiency in development of structure derived from the ectoderm and is caused by mutations in the genes EDA, EDAR, or EDARADD. Phenotypes caused by mutations in these three may exhibit similar clinical features, explained by a common signaling pathway. Mutations in EDA gene cause X linked HED, which is the most common form. Mutations in EDAR and EDARADD genes cause autosomal dominant and recessive form of HED. The most striking clinical findings in HED are hypodontia, hypotrichosis and hypohidrosis that can lead to episodes of hyperthermia. We report on clinical findings in a child with HED with autosomal dominant inheritance pattern with a heterozygous mutation c.1072C>T (p.Arg358X) in the EDAR gene. A review of the literature with regard to other cases presenting the same mutation has been carried out and discussed. Sociedad Argentina de Pediatría.

  2. Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

    Directory of Open Access Journals (Sweden)

    Kana Tanahashi

    Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

  3. Alternative prosthodontic-based treatment of a patient with hypocalcified type Amelogenesis Imperfecta.

    Science.gov (United States)

    Jivanescu, Anca; Miglionico, Antonio; Barua, Souman; Hategan, Simona Ioana

    2017-07-01

    The Amelogenesis Imperfecta is associated with malocclusion and usually requires an interdisciplinary treatment. Due to the patient's refusal of orthodontic treatment, prosthodontics-based treatments alternative was considered and planned. The patient was treated with zirconia-based fixed partial dentures, which resulted in improved occlusion, better oral health, and improved esthetic appearance.

  4. [From gene to disease: from the ABCA4 gene to Stargardt disease, cone-rod dystrophy and retinitis pigmentosa

    NARCIS (Netherlands)

    Cremers, F.P.M.; Maugeri, A.; Klevering, B.J.; Hoefsloot, L.H.; Hoyng, C.B.

    2002-01-01

    Autosomal recessive Stargardt disease is caused by mutations in the ABCA4 gene. Mutations in ABCA4 are also found in two-thirds of cases with autosomal recessive cone-rod dystrophy, and a small fraction of patients with autosomal recessive retinitis pigmentosa. Patients with autosomal recessive

  5. Impact of moderate and severe hypodontia and amelogenesis imperfecta on quality of life and self-esteem of adult patients.

    Science.gov (United States)

    Hashem, Atef; Kelly, Alan; O'Connell, Brian; O'Sullivan, Michael

    2013-08-01

    The objective of this study was to investigate the impact of moderate and severe hypodontia and amelogenesis imperfecta on the quality of life and self-esteem of affected adult patients. Forty one adult patients (aged 18-45 years) with clinical and radiological diagnoses of moderate to severe hypodontia and twenty seven patients diagnosed with amelogenesis imperfecta were age and gender matched with a control group of patients attending for routine dental care. Subjects completed the Oral Health Impact Profile [OHIP-49] and Rosenberg Self Esteem Scale. A paired t-test was used to analyse data; the test alpha level was set at P ≤ 0.05. The results for hypodontia patients were significantly different from controls in six out of the seven OHIP-49 domains, the exception being the Handicap domain. Total scores were also significantly different between the two groups (P=0.003). Self-esteem was not significantly different between the two groups (P=0.98). For amelogenesis imperfecta patients the results were significantly different from control patients in four out of the seven domains of the OHIP-49 and also in the total scores (P=0.01). When self-esteem was investigated there was no significant differences between the two groups (P=0.92). Moderate to severe hypodontia and amelogenesis imperfecta have marked negative impacts on the Oral Health Related quality of life of this patient population relative to controls. However, self-esteem was not significantly affected. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Autosomal Recessive Inheritance

    Science.gov (United States)

    ... NEI Intranet (Employees Only) *PDF files require the free Adobe® Reader® software for viewing. This website is maintained by the NEI Office of Science Communications, Public Liaison, and Education. Technical questions about this website can be addressed ...

  7. Skeletal muscle, but not cardiovascular function, is altered in a mouse model of autosomal recessive hypophosphatemic rickets

    Directory of Open Access Journals (Sweden)

    Michael J. Wacker

    2016-05-01

    Full Text Available Autosomal recessive hypophosphatemic rickets (ARHR is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL- fast-twitch muscle, soleus (SOL- slow-twitch muscle, heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2a or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In

  8. AUTOSOMAL RECESSIVE PERIPHERAL NEUROPATHY WITH NEUROMYOTONIA (ARAN-NM: DESCRIPTION OF A CLINICAL CASE CONFIRMED BY A MUTATION IN THE HINT1 GENE

    Directory of Open Access Journals (Sweden)

    Olga A. Klochkova

    2017-01-01

    Full Text Available Autosomal recessive  peripheral neuropathy with neuromyotonia  (ARAN-NM  is a relatively newly described  disease associated  with mutations  in the HINT1 gene.  It accounts  for a significant  part of the poorly  differentiated  forms  of axonal polyneuropathies.  We present the first in Russia description of the genetically confirmed case of ARAN-NM in a boy aged 14 years and 11 months without the hereditary-tainted anamnesis. On presentation,  the patient experienced  progressive  distal muscular weakness, asymmetric foot deformity,  gait disorders  and minimal manifestations  of neuromyotonia  (stiffness  in the fingers.  During examination,  we detected an increase in the level of creatine phosphokinase up to 635 U/l, a disturbance of conduction of motor and, to a lesser extent, sensory fibers  of  the  peripheral  nerves  (according  to  the  stimulation  electromyography,  EMG,  denervation-reinnervation  changes,  single positive acute waves, fibrillation potentials, complex repeated discharge (according to the data of needle EMG. In the study of exome, a homozygous mutation c.110G>C, p.R37P was determined in exon 01 of the HINT1 gene, which confirmed the presence of ARAN-NM. A molecular-genetic  examination of the patient's immediate relatives was carried out. The described case is compared with literature data. An overview of currently available information on ARAN-NM is provided. Diagnostic criteria of the disease are presented.

  9. Mutant Runx2 regulates amelogenesis and osteogenesis through a miR-185-5p-Dlx2 axis.

    Science.gov (United States)

    Chang, Huaiguang; Wang, Yue; Liu, Haochen; Nan, Xu; Wong, Singwai; Peng, Saihui; Gu, Yajuan; Zhao, Hongshan; Feng, Hailan

    2017-12-14

    Regulation of microRNAs (miRNA) has been extensively investigated in diseases; however, little is known about the roles of miRNAs in cleidocranial dysplasia (CCD). The aim of the present study was to investigate the potential involvement of miRNAs in CCD. In vitro site-directed mutagenesis was performed to construct three mutant Runx2 expression vectors, which were then transfected into LS8 cells and MC3T3-E1 cells, to determine the impact on amelogenesis and osteogenesis, respectively. miRCURY LNA miRNA microarray identify miR-185-5p as a miRNA target commonly induced by all three Runx2 mutants. Real-time quantitative PCR was applied to determine the expression of miR-185-5p and Dlx2 in samples. Dual-luciferase reporter assays were conducted to confirm Dlx2 as a legitimate target of miR-185-5p. The suppressive effect of miR-185-5p on amelogenesis and osteogenesis of miR-185-5p was evaluated by RT-PCR and western blot examination of Amelx, Enam, Klk4, and Mmp20 gene and protein expression, and by Alizarin Red stain. We found that mutant Runx2 suppressed amelogenesis and osteogenesis. miR-185-5p, induced by Runx2, suppressed amelogenesis and osteogenesis. Furthermore, we identified Dlx2 as direct target of miR-185-5p. Consistently, Dlx2 expression was inversely correlated with miR-185-5p levels. This study highlights the molecular etiology and significance of miR-185-5p in CCD, and suggests that targeting miR-185-5p may represent a new therapeutic strategy in prevention or intervention of CCD.

  10. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.

    Science.gov (United States)

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L; Hacia, Joseph G; Paine, Michael L

    2017-03-13

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

  11. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

    Science.gov (United States)

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

    2017-01-01

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

  12. Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays.

    Science.gov (United States)

    H'mida-Ben Brahim, D; M'zahem, A; Assoum, M; Bouhlal, Y; Fattori, F; Anheim, M; Ali-Pacha, L; Ferrat, F; Chaouch, M; Lagier-Tourenne, C; Drouot, N; Thibaut, C; Benhassine, T; Sifi, Y; Stoppa-Lyonnet, D; N'Guyen, K; Poujet, J; Hamri, A; Hentati, F; Amouri, R; Santorelli, F M; Tazir, M; Koenig, M

    2011-01-01

    The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents. Patients from 97 families were analyzed with GeneChip Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families homozygous for regions containing the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia-telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2) gene. Upon direct gene testing, we were able to identify a disease-related mutation in all families but one of the two kindred homozygous at the ATM locus. Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1 for this family, clinical features, normal levels of serum alpha-foetoprotein as well as absence of mutations in the ATM gene rather suggest the existence of an additional ARCA-related gene in that interval. While the use of homozygosity mapping was very effective at pointing to the correct gene, it also suggests that the majority of patients harbor mutations either in the genes of the rare forms of ARCA or in genes yet to be identified.

  13. Chairside treatment of amelogenesis imperfecta, including establishment of a new vertical dimension with resin nanoceramic and intraoral scanning.

    Science.gov (United States)

    Zimmermann, Moritz; Koller, Christina; Hickel, Reinhard; Kühnisch, Jan

    2016-09-01

    Amelogenesis imperfecta is a hereditary disease affecting the structural development of tooth substance. This clinical report describes a 1-visit chairside treatment of an 8-year-old patient with amelogenesis imperfecta, using computer-aided design and computer-aided manufacturing (CAD-CAM) technology. Intraoral scanning was performed using the Cerec Omnicam. Thirteen resin nanoceramic crowns (Lava Ultimate) were fabricated chairside by using a Cerec MCXL milling unit and seated adhesively. The patient's treatment included establishing a new occlusal vertical dimension and new centric relationship. Reevaluation after 6 months showed a stable situation. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  14. NCBI nr-aa BLAST: CBRC-FCAT-01-1153 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 1| polycystic kidney and hepatic disease 1 [Homo sapiens] emb|CAH73867.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAH72781.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI16676.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI20324.1| polycystic kidney and hepatic disease 1 (autosomal r...ecessive) [Homo sapiens] emb|CAI20233.1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_619639.3 0.0 76% ...

  15. NCBI nr-aa BLAST: CBRC-CJAC-01-1207 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available 1| polycystic kidney and hepatic disease 1 [Homo sapiens] emb|CAH73867.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAH72781.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI16676.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI20324.1| polycystic kidney and hepatic disease 1 (autosomal r...ecessive) [Homo sapiens] emb|CAI20233.1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_619639.3 0.0 87% ...

  16. A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome.

    Science.gov (United States)

    Bicknell, Louise S; Pitt, James; Aftimos, Salim; Ramadas, Ram; Maw, Marion A; Robertson, Stephen P

    2008-10-01

    There are several rare syndromes combining wrinkled, redundant skin and neurological abnormalities. Although phenotypic overlap between conditions has suggested that some might be allelic to one another, the aetiology for many of them remains unknown. A consanguineous New Zealand Maori family has been characterised that segregates an autosomal recessive connective tissue disorder (joint dislocations, lax skin) associated with neurological abnormalities (severe global developmental delay, choreoathetosis) without metabolic abnormalities in four affected children. A genome-screen performed under a hypothesis of homozygosity by descent for an ancestral mutation, identified a locus at 10q23 (Z = 3.63). One gene within the candidate interval, ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), was considered a plausible disease gene since a missense mutation had previously been shown to cause progressive neurodegeneration, cataracts, skin laxity, joint dislocations and metabolic derangement in a consanguineous Algerian family. A missense mutation, 2350C>T, was identified in ALDH18A1, which predicts the substitution H784Y. H784 is invariant across all phyla and lies within a previously unrecognised, conserved C-terminal motif in P5CS. In an in vivo assay of flux through this metabolic pathway using dermal fibroblasts obtained from an affected individual, proline and ornithine biosynthetic activity of P5CS was not affected by the H784Y substitution. These data suggest that P5CS may possess additional uncharacterised functions that affect connective tissue and central nervous system function.

  17. Missense Mutations in CRYAB Are Liable for Recessive Congenital Cataracts.

    Directory of Open Access Journals (Sweden)

    Xiaodong Jiao

    Full Text Available This study was initiated to identify causal mutations responsible for autosomal recessive congenital cataracts in consanguineous familial cases.Affected individuals underwent a detailed ophthalmological and clinical examination, and slit-lamp photographs were ascertained for affected individuals who have not yet been operated for the removal of the cataractous lens. Blood samples were obtained, and genomic DNA was extracted from white blood cells. A genome-wide scan was completed with short tandem repeat (STR markers, and the logarithm of odds (LOD scores were calculated. Protein coding exons of CRYAB were sequenced, bi-directionally. Evolutionary conservation was investigated by aligning CRYAB orthologues, and the expression of Cryab in embryonic and postnatal mice lens was investigated with TaqMan probe.The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis suggested a potential region on chromosome 11q23 harboring CRYAB. DNA sequencing identified a missense variation: c.34C>T (p.R12C in CRYAB that segregated with the disease phenotype in the family. Subsequent interrogation of our entire cohort of familial cases identified a second familial case localized to chromosome 11q23 harboring a c.31C>T (p.R11C mutation. In silico analyses suggested that the mutations identified in familial cases, p.R11C and p.R12C will not be tolerated by the three-dimensional structure of CRYAB. Real-time PCR analysis identified the expression of Cryab in mouse lens as early as embryonic day 15 (E15 that increased significantly until postnatal day 6 (P6 with steady level of expression thereafter.Here, we report two novel missense mutations, p.R11C and p.R12C, in CRYAB associated with autosomal recessive congenital nuclear cataracts.

  18. Comparative expression of the four enamel matrix protein genes, amelogenin, ameloblastin, enamelin and amelotin during amelogenesis in the lizard Anolis carolinensis.

    Science.gov (United States)

    Gasse, Barbara; Sire, Jean-Yves

    2015-01-01

    In a recent study, we have demonstrated that amelotin (AMTN) gene structure and its expression during amelogenesis have changed during tetrapod evolution. Indeed, this gene is expressed throughout enamel matrix deposition and maturation in non-mammalian tetrapods, while in mammals its expression is restricted to the transition and maturation stages of amelogenesis. Previous studies of amelogenin (AMEL) gene expression in a lizard and a salamander have shown similar expression pattern to that in mammals, but to our knowledge there are no data regarding ameloblastin (AMBN) and enamelin (ENAM) expression in non-mammalian tetrapods. The present study aims to look at, and compare, the structure and expression of four enamel matrix protein genes, AMEL, AMBN, ENAM and AMTN during amelogenesis in the lizard Anolis carolinensis. We provide the full-length cDNA sequence of A. carolinensis AMEL and AMBN, and show for the first time the expression of ENAM and AMBN in a non-mammalian species. During amelogenesis in A. carolinensis, AMEL, AMBN and ENAM expression in ameloblasts is similar to that described in mammals. It is noteworthy that AMEL and AMBN expression is also found in odontoblasts. Our findings indicate that AMTN is the only enamel matrix protein gene that is differentially expressed in ameloblasts between mammals and sauropsids. Changes in AMTN structure and expression could be the key to explain the structural differences between mammalian and reptilian enamel, i.e. prismatic versus non-prismatic.

  19. Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Bisgaard, A-M; Kirchhoff, M; Nielsen, J E

    2008-01-01

    A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA......) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA....

  20. The Role of Epithelial Stat3 in Amelogenesis during Mouse Incisor Renewal.

    Science.gov (United States)

    Zhang, Bin; Meng, Bo; Viloria, Edward; Naveau, Adrien; Ganss, Bernhard; Jheon, Andrew H

    2018-03-16

    The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14Cre/+;Stat3fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis. © 2018 S. Karger AG, Basel.

  1. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

    Science.gov (United States)

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

    2016-01-01

    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information.

  2. Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa.

    Science.gov (United States)

    Paterson, Rachel L; De Roach, John N; McLaren, Terri L; Hewitt, Alex W; Hoffmann, Ling; Lamey, Tina M

    2012-01-01

    Retinitis pigmentosa (RP) is the most common form of inherited blindness, caused by progressive degeneration of photoreceptor cells in the retina, and affects approximately 1 in 3,000 people. Over the past decade, significant progress has been made in gene therapy for RP and related diseases, making genetic characterization increasingly important. Recently, high-throughput technologies have provided an option for reasonably fast, cost-effective genetic characterization of autosomal recessive RP (arRP). The current study used a single nucleotide polymorphism (SNP) genotyping method to exclude up to 28 possible disease-causing genes in 31 non-consanguineous Australian families affected by arRP. DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses. Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (pA) and USH2A in two families (c.2276 G>T). This study has shown that SNP genotyping cosegregation analysis can be successfully used to refine and expedite the genetic characterization of arRP in a non-consanguineous population; however, this method is effective only when DNA samples are

  3. Treatment plan in amelogenesis imperfecta: A structured literature review on treatment protocols and dedicating the best possible options

    Directory of Open Access Journals (Sweden)

    Azari A.

    2008-12-01

    Full Text Available "nAmelogenesis imperfecta is an inherited disease that disturbs the formation of the enamel. It occurs as two main categories, hypomineralized and hypoplastic. Both deciduous and permanent teeth are affected, and the disorder may create unaesthetic appearance, dental sensitivity, and severe attrition. In this article through performing a structured literature review, numerous treatment modalities which so far advocated in rehabilitation of amelogenesis imperfecta in adults and children is discussed. The progressive changes on open bite, the problem of bonding during restorative phase of treatment , the rehabilitation difficulties of deciduous as well as permanent teeth is also discussed in detail and finally the interdisciplinary approach for treatment of this disability is demonstrated and some points for decision making in treatment protocols are suggested.

  4. Mineral features of connective dental hard tissues in hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Kammoun, R; Behets, C; Mansour, L; Ghoul-Mazgar, S

    2018-04-01

    To explore the mineral features of dentin and cementum in hypoplastic Amelogenesis imperfecta AI teeth. Forty-four (44) teeth cleaned and free of caries were used: 20 control and 24 affected by hypoplastic amelogenesis imperfecta. Thirty-two teeth were studied by pQCT, cut in sections, and analyzed under microradiography, polarized light microscopy, and confocal Raman spectroscopy. Eight teeth were observed under scanning electron microscope. Four teeth were used for an X-ray diffraction. The mineral density data were analyzed statistically with the Mann-Whitney U test, using GraphPad InStat software. Both coronal dentin and radicular dentin were less mineralized in AI teeth when compared to control (respectively 6.2% and 6.8%; p < .001). Root dentinal walls were thin and irregular, while the cellular cementum layers were thick, reaching sometimes the cervical region of the tooth. Regular dentinal tubules and sclerotic dentin areas were noticed. Partially tubular or cellular dysplastic dentin and hyper-, normo-, or hypomineralized areas were noticed in the inter-radicular areas of hypoplastic AI teeth. The main mineral component was carbonate hydroxyapatite as explored by Raman spectroscopy and X-ray diffraction. Dentin and cementum in hypoplastic AI teeth are (i) hypomineralized, (ii) constituted of carbonate hydroxyapatite, and (iii) of non-homogenous structure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  5. Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

    Science.gov (United States)

    2017-09-28

    -Hirschhorn Syndrome; 4p16.3 Microduplication Syndrome; 4p Deletion Syndrome, Non-Wolf-Hirschhorn Syndrome; Autosomal Recessive Stickler Syndrome; Stickler Syndrome Type 2; Stickler Syndrome Type 1; Stickler Syndrome; Mucolipidosis Type 4; X-linked Spinocerebellar Ataxia Type 4; X-linked Spinocerebellar Ataxia Type 3; X-linked Intellectual Disability - Ataxia - Apraxia; X-linked Progressive Cerebellar Ataxia; X-linked Non Progressive Cerebellar Ataxia; X-linked Cerebellar Ataxia; Vitamin B12 Deficiency Ataxia; Toxic Exposure Ataxia; Unclassified Autosomal Dominant Spinocerebellar Ataxia; Thyroid Antibody Ataxia; Sporadic Adult-onset Ataxia of Unknown Etiology; Spinocerebellar Ataxia With Oculomotor Anomaly; Spinocerebellar Ataxia With Epilepsy; Spinocerebellar Ataxia With Axonal Neuropathy Type 2; Spinocerebellar Ataxia Type 8; Spinocerebellar Ataxia Type 7; Spinocerebellar Ataxia Type 6; Spinocerebellar Ataxia Type 5; Spinocerebellar Ataxia Type 4; Spinocerebellar Ataxia Type 37; Spinocerebellar Ataxia Type 36; Spinocerebellar Ataxia Type 35; Spinocerebellar Ataxia Type 34; Spinocerebellar Ataxia Type 32; Spinocerebellar Ataxia Type 31; Spinocerebellar Ataxia Type 30; Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 29; Spinocerebellar Ataxia Type 28; Spinocerebellar Ataxia Type 27; Spinocerebellar Ataxia Type 26; Spinocerebellar Ataxia Type 25; Spinocerebellar Ataxia Type 23; Spinocerebellar Ataxia Type 22; Spinocerebellar Ataxia Type 21; Spinocerebellar Ataxia Type 20; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 19/22; Spinocerebellar Ataxia Type 18; Spinocerebellar Ataxia Type 17; Spinocerebellar Ataxia Type 16; Spinocerebellar Ataxia Type 15/16; Spinocerebellar Ataxia Type 14; Spinocerebellar Ataxia Type 13; Spinocerebellar Ataxia Type 12; Spinocerebellar Ataxia Type 11; Spinocerebellar Ataxia Type 10; Spinocerebellar Ataxia Type 1 With Axonal Neuropathy; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia - Unknown; Spinocerebellar Ataxia - Dysmorphism

  6. Functions of KLK4 and MMP-20 in dental enamel formation

    Science.gov (United States)

    Lu, Yuhe; Papagerakis, Petros; Yamakoshi, Yasuo; Hu, Jan C-C.; Bartlett, John D.; Simmer, James P.

    2009-01-01

    Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. Kallikrein 4 is secreted by transition and maturation stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins. PMID:18627287

  7. FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

    Directory of Open Access Journals (Sweden)

    Guilhem Lignon

    2017-05-01

    Full Text Available Background and objective:FAM20A gene mutations result in enamel renal syndrome (ERS associated with amelogenesis imperfecta (AI, nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects.Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM, Energy Dispersive Spectroscopy (EDS, X-Ray Diffraction (XRD, and X-Ray Fluorescence (XRF.Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel. XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin.Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant.

  8. FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

    Science.gov (United States)

    Lignon, Guilhem; Beres, Fleur; Quentric, Mickael; Rouzière, Stephan; Weil, Raphael; De La Dure-Molla, Muriel; Naveau, Adrien; Kozyraki, Renata; Dessombz, Arnaud; Berdal, Ariane

    2017-01-01

    Background and objective: FAM20A gene mutations result in enamel renal syndrome (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects. Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and X-Ray Fluorescence (XRF). Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction) displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel). XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin. Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant.

  9. Rehabilitation of a patient with amelogenesis imperfecta using porcelain veneers and CAD/CAM polymer restorations: A clinical report.

    Science.gov (United States)

    Saeidi Pour, Reza; Edelhoff, Daniel; Prandtner, Otto; Liebermann, Anja

    2015-01-01

    The complete dental rehabilitation of patients with a vertical dimension loss (VDL) caused by structural enamel deficits associated with amelogenesis imperfecta (AI) represents a difficult challenge for restorative teams. Accurate analysis and treatment planning that includes esthetic and functional evaluations and adequate material selection are important prerequisites for successful results. Long-term provisional restorations play an important role in exploring and elucidating the patients' esthetic demands and functional needs. Restorative treatment options can vary from requiring only oral hygiene instructions to extensive dental restorations that include composite fillings, ceramic veneers, metal-ceramic, or all-ceramic crowns. This case report describes a full-mouth rehabilitation of a patient with amelogenesis imperfecta including the case planning, bite replacement, preparation, and restoration setting steps with an experimental CAD/CAM polymer and porcelain veneers.

  10. Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.

    Science.gov (United States)

    Riveiro-Alvarez, Rosa; Lopez-Martinez, Miguel-Angel; Zernant, Jana; Aguirre-Lamban, Jana; Cantalapiedra, Diego; Avila-Fernandez, Almudena; Gimenez, Ascension; Lopez-Molina, Maria-Isabel; Garcia-Sandoval, Blanca; Blanco-Kelly, Fiona; Corton, Marta; Tatu, Sorina; Fernandez-San Jose, Patricia; Trujillo-Tiebas, Maria-Jose; Ramos, Carmen; Allikmets, Rando; Ayuso, Carmen

    2013-11-01

    To provide a comprehensive overview of all detected mutations in the ABCA4 gene in Spanish families with autosomal recessive retinal disorders, including Stargardt's disease (arSTGD), cone-rod dystrophy (arCRD), and retinitis pigmentosa (arRP), and to assess genotype-phenotype correlation and disease progression in 10 years by considering the type of variants and age at onset. Case series. A total of 420 unrelated Spanish families: 259 arSTGD, 86 arCRD, and 75 arRP. Spanish families were analyzed through a combination of ABCR400 genotyping microarray, denaturing high-performance liquid chromatography, and high-resolution melting scanning. Direct sequencing was used as a confirmation technique for the identified variants. Screening by multiple ligation probe analysis was used to detect possible large deletions or insertions in the ABCA4 gene. Selected families were analyzed further by next generation sequencing. DNA sequence variants, mutation detection rates, haplotypes, age at onset, central or peripheral vision loss, and night blindness. Overall, we detected 70.5% and 36.6% of all expected ABCA4 mutations in arSTGD and arCRD patient cohorts, respectively. In the fraction of the cohort where the ABCA4 gene was sequenced completely, the detection rates reached 73.6% for arSTGD and 66.7% for arCRD. However, the frequency of possibly pathogenic ABCA4 alleles in arRP families was only slightly higher than that in the general population. Moreover, in some families, mutations in other known arRP genes segregated with the disease phenotype. An increasing understanding of causal ABCA4 alleles in arSTGD and arCRD facilitates disease diagnosis and prognosis and also is paramount in selecting patients for emerging clinical trials of therapeutic interventions. Because ABCA4-associated diseases are evolving retinal dystrophies, assessment of age at onset, accurate clinical diagnosis, and genetic testing are crucial. We suggest that ABCA4 mutations may be associated with a

  11. The Great Recession: a comparison of recession magnitudes in Europe, USA and Japan

    OpenAIRE

    Mazurek, Jiří

    2013-01-01

    In this article recession magnitudes in Europe, the USA and Japan during the Great Recession are compared. The strongest recessions (of severe category) occurred in Latvia, Lithuania and Estonia, while recessions in Japan and the USA were significantly weaker. Even the strongest recession (in Latvia) was found smaller in its magnitude than the Great Depression 1929-1933 in the USA. Hence, comparisons of the Great Recession to the Great Depression in the literature are somewhat exaggerated.

  12. Bilateral nephrocalcinosis and amelogenesis imperfecta: A case report

    Directory of Open Access Journals (Sweden)

    Alok Patel

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of nonconsanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with a generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a Nephrologist. Children with nephrocalcinosis should also be considered for a dental check.

  13. Structure of initial crystals formed during human amelogenesis

    Science.gov (United States)

    Cuisinier, F. J. G.; Voegel, J. C.; Yacaman, J.; Frank, R. M.

    1992-02-01

    X-ray diffraction analysis revealed only the existence of carbonated hydroxyapatite (c.HA) during amelogenesis, whereas conventional transmission electron microscopy investigations showed that developing enamel crystals have a ribbon-like habit. The described compositional changes could be an indication for the presence of minerals different from c.HA. However, the absence of identification of such a mineral shows the need of studies by high resolution electron microscopy (HREM) of initial formed human enamel crystals. We demonstrate the existence of two crystal families involved in the early stages of biomineralization: (a) nanometer-size particles which appeared as a precursor phase; (b) ribbon-like crystals, with a structure closely related to c.HA, which by a progressive thickening process tend to attain the mature enamel crystal habit.

  14. Forecasting US Recessions

    DEFF Research Database (Denmark)

    Christiansen, Charlotte; Eriksen, Jonas Nygaard; Møller, Stig Vinther

    2014-01-01

    We study the role of sentiment variables as predictors for US recessions. We combine sentiment variables with either classical recession predictors or common factors based on a large panel of macroeconomic and financial variables. Sentiment variables hold vast predictive power for US recessions...

  15. Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Hama, Taketsugu; Nakanishi, Koichi; Sato, Masashi; Mukaiyama, Hironobu; Togawa, Hiroko; Shima, Yuko; Miyajima, Masayasu; Nozu, Kandai; Nagao, Shizuko; Takahashi, Hisahide; Sako, Mayumi; Iijima, Kazumoto; Yoshikawa, Norishige; Suzuki, Hiroyuki

    2017-12-01

    Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-β/Smad3 signaling is involved; however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-β/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-β, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. α-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts; however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/ cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-β/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention. Copyright © 2017 the American Physiological Society.

  16. HUMAN CELLS IN CULTURE: REVISlTED*

    African Journals Online (AJOL)

    advantages, e.g. the generation time is reduced to about. 1/10000 that of the ... or less reflects the cellular biology of the donor tissut:'Y .... X-linked. Autosomal recessive. Autosomal recessive. Autosomal recessive mothers of affected males, however, show that only 50% of the cell population is defective, which furnishes an.

  17. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.

    Science.gov (United States)

    Ballew, Bari J; Joseph, Vijai; De, Saurav; Sarek, Grzegorz; Vannier, Jean-Baptiste; Stracker, Travis; Schrader, Kasmintan A; Small, Trudy N; O'Reilly, Richard; Manschreck, Chris; Harlan Fleischut, Megan M; Zhang, Liying; Sullivan, John; Stratton, Kelly; Yeager, Meredith; Jacobs, Kevin; Giri, Neelam; Alter, Blanche P; Boland, Joseph; Burdett, Laurie; Offit, Kenneth; Boulton, Simon J; Savage, Sharon A; Petrini, John H J

    2013-08-01

    Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.

  18. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.

    Directory of Open Access Journals (Sweden)

    Bari J Ballew

    2013-08-01

    Full Text Available Dyskeratosis congenita (DC is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.

  19. Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa.

    Science.gov (United States)

    Méndez-Vidal, Cristina; González-Del Pozo, María; Vela-Boza, Alicia; Santoyo-López, Javier; López-Domingo, Francisco J; Vázquez-Marouschek, Carmen; Dopazo, Joaquin; Borrego, Salud; Antiñolo, Guillermo

    2013-01-01

    Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data

  20. Quantitative electron microscopical autoradiography of calcium during amelogenesis

    International Nuclear Information System (INIS)

    Nagai, Yoshinori; Frank, R.M.

    1975-01-01

    The migration of 45 Ca through the stratum intermedium and through the secreting ameloblasts towards enamel has been studied by electron microscopical autoradiography in the toothgerms of newborn cats. A quantitative procedure was applied to the study of the 45 Ca migration in amelogenesis and two pathways were demonstrated. The relatively more important direct route passed through the stratum intermedium and the ameloblast intercellular spaces and reached the enamel directly. The second pathway consisted of an intracellular migration through the ameloblast. 45 Ca penetrated the cell through its basal pole. The mitochondrias were the most highly labeled organelles at the different experimental time intervals studied. A total absence of silver grains was noted over the secretory ameloblastic bodies. At 6 hours, the highest labeling was observed over enamel. (auth.)

  1. NCBI nr-aa BLAST: CBRC-FCAT-01-1153 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available .1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAH72782.1| polycystic ...kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAI16677.1| polycystic kidney and hepatic disease 1 (autos...ney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_733842.2 0.0 76% ...

  2. NCBI nr-aa BLAST: CBRC-CJAC-01-1207 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available .1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAH72782.1| polycystic ...kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAI16677.1| polycystic kidney and hepatic disease 1 (autos...ney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_733842.2 0.0 87% ...

  3. Prosthetic and Surgical Approach for Oral Rehabilitation in a Patient with Amelogenesis Imperfecta: A Clinical Report

    Directory of Open Access Journals (Sweden)

    H. Sazegara

    2007-06-01

    Full Text Available Amelogenesis imperfecta is a heterogeneous group of hereditary disorders. Its treatment continues throughout the patients’ childhood and adolescence and consists of advanced restorative care in severe cases.A thorough prosthodontic treatment plan including orthognatic surgery, full veneer crowns and all ceramic anterior crowns is presented in this clinical report.

  4. Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

    Science.gov (United States)

    Jacobsen, Jessie C; Whitford, Whitney; Swan, Brendan; Taylor, Juliet; Love, Donald R; Hill, Rosamund; Molyneux, Sarah; George, Peter M; Mackay, Richard; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

    2017-11-21

    Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ 10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q 10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ 10, and the siblings were subsequently established on a therapeutic dose of CoQ 10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

  5. Congenital sensorineural deafness in Australian stumpy-tail cattle dogs is an autosomal recessive trait that maps to CFA10.

    Directory of Open Access Journals (Sweden)

    Susan Sommerlad

    2010-10-01

    speckling. Fine mapping was then performed on 45 of these 50 dogs and a further 48 dogs (n = 93. Sequencing candidate gene Sox10 in 6 hearing ASCD, 2 unilaterally deaf ASCD and 2 bilaterally deaf ASCD did not reveal any disease-associated mutations.Deafness in ASCD is an incompletely penetrant autosomal recessive inherited disease that maps to CFA10.

  6. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association

    Directory of Open Access Journals (Sweden)

    P Ravi

    2013-01-01

    Full Text Available Renal tubular acidosis (RTA is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI.

  7. Expression of steroid receptors in ameloblasts during amelogenesis in rat incisors

    Directory of Open Access Journals (Sweden)

    Sophia Houari

    2016-11-01

    Full Text Available Endocrine disrupting chemicals (EDCs play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA, one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH. In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30, of ketosteroid receptors (ERs, AR, PGR, GR, MR, of the retinoid receptor RXRα and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR, whereas the others were 13 to 612 fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step towards understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis.

  8. Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors.

    Science.gov (United States)

    Houari, Sophia; Loiodice, Sophia; Jedeon, Katia; Berdal, Ariane; Babajko, Sylvie

    2016-01-01

    Endocrine disrupting chemicals (EDCs) play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA), one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH). In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30), of ketosteroid receptors (ERs, AR, PGR, GR, MR), of the retinoid receptor RXRα, and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation-stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR), whereas the others were 13 to 612-fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step toward understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis.

  9. Genome-wide analysis of miRNA and mRNA transcriptomes during amelogenesis.

    Science.gov (United States)

    Yin, Kaifeng; Hacia, Joseph G; Zhong, Zhe; Paine, Michael L

    2014-11-19

    In the rodent incisor during amelogenesis, as ameloblast cells transition from secretory stage to maturation stage, their morphology and transcriptome profiles change dramatically. Prior whole genome transcriptome analysis has given a broad picture of the molecular activities dominating both stages of amelogenesis, but this type of analysis has not included miRNA transcript profiling. In this study, we set out to document which miRNAs and corresponding target genes change significantly as ameloblasts transition from secretory- to maturation-stage amelogenesis. Total RNA samples from both secretory- and maturation-stage rat enamel organs were subjected to genome-wide miRNA and mRNA transcript profiling. We identified 59 miRNAs that were differentially expressed at the maturation stage relative to the secretory stage of enamel development (False Discovery Rate (FDR)<0.05, fold change (FC)≥1.8). In parallel, transcriptome profiling experiments identified 1,729 mRNA transcripts that were differentially expressed in the maturation stage compared to the secretory stage (FDR<0.05, FC≥1.8). Based on bioinformatics analyses, 5.8% (629 total) of these differentially expressed genes (DEGS) were highlighted as being the potential targets of 59 miRNAs that were differentially expressed in the opposite direction, in the same tissue samples. Although the number of predicted target DEGs was not higher than baseline expectations generated by examination of stably expressed miRNAs, Gene Ontology (GO) analysis showed that these 629 DEGS were enriched for ion transport, pH regulation, calcium handling, endocytotic, and apoptotic activities. Seven differentially expressed miRNAs (miR-21, miR-31, miR-488, miR-153, miR-135b, miR-135a and miR298) in secretory- and/or maturation-stage enamel organs were confirmed by in situ hybridization. Further, we used luciferase reporter assays to provide evidence that two of these differentially expressed miRNAs, miR-153 and miR-31, are potential

  10. Amelogenesis Imperfecta and Screening of Mutation in Amelogenin Gene

    Directory of Open Access Journals (Sweden)

    Fernanda Veronese Oliveira

    2014-01-01

    Full Text Available The aim of this study was to report the clinical findings and the screening of mutations of amelogenin gene of a 7-year-old boy with amelogenesis imperfecta (AI. The genomic DNA was extracted from saliva of patient and his family, followed by PCR and direct DNA sequencing. The c.261C>T mutation was found in samples of mother, father, and brother, but the mutation was not found in the sequence of the patient. This mutation is a silent mutation and a single-nucleotide polymorphism (rs2106416. Thus, it is suggested that the mutation found was not related to the clinical presence of AI. Further research is necessary to examine larger number of patients and genes related to AI.

  11. Oral rehabilitation of primary dentition affected by amelogenesis imperfecta: a case report.

    Science.gov (United States)

    de Souza-e-Silva, Cíntia Maria; Parisotto, Thaís Manzano; Steiner-Oliveira, Carolina; Gavião, Maria Beatriz Duarte; Nobre-Dos-Santos, Marinês

    2010-05-01

    The purpose of the case report was to describe the treatment of a 4(1/2)-year-old boy with amelogenesis imperfect (AI) in the primary dentition. AI is a hereditary condition that affects the development of enamel, causing quantity, structural, and compositional anomalies involving all dentitions. Consequently, the effects can extend to both the primary and secondary dentitions. A 4(1/2)-year-old boy was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of amelogenesis imperfecta. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms of both maxillary and mandibular primary incisors and canines. Improvements in the patient's psychological behavior and the elimination of tooth sensitiveness were observed, and the reestablishment of a normal occlusion resulted in improved eating habits. The child was monitored in the Pediatric Dentistry Clinic at four-month intervals until the mixed dentition stage. The oral rehabilitation of young children with AI is necessary to reestablish the stomatognathic system function, so important for a child's systemic health. An adequate medical history and a careful clinical examination were essential for a correct diagnosis. Treatment was rendered that was appropriate for the child's age and clinical/psychological characteristics. Cost-effective restorative techniques involving stainless steel and composite-resin crowns are shown for the restoration of a young patient with amelogensis imperfecta.

  12. Autosomal dominant Carvajal plus syndrome due to the novel desmoplakin mutation c.1678A > T (p.Ile560Phe).

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia; Wollmann, Eva; Dertinger, Susanne; Laccone, Franco

    2016-09-01

    Carvajal syndrome is an autosomal dominant or autosomal recessive disorder, manifesting with dilated cardiomyopathy, woolly hair, and palmoplantar keratoma. Additional manifestations can be occasionally found. Carvajal syndrome may be due to mutations in the desmocollin-2, desmoplakin, or plakophilin-2 gene. We report a family with Carvajal syndrome which additionally presented with hypoacusis, noncompaction, recurrent pharyngeal infections, oligodontia, and recurrent diarrhoea. Father and brother were also affected and had died suddenly, the father despite implantation of a cardioverter defibrillator (ICD). Genetic studies revealed the novel pathogenic mutation c.1678A > T in the desmoplakin gene resulting in the amino acid change Ile to Phe at position 560 in the index case and her brother. The index case underwent ICD implantation recently. Phenotypic manifestations of Carvajal syndrome are even broader than so far anticipated, the number of mutations in the desmoplakin gene responsible for Carvajal syndrome is still increasing, and these patients require implantation of an ICD as soon as their diagnosis is established.

  13. Simple Y-autosomal incompatibilities cause hybrid male sterility in reciprocal crosses between Drosophila virilis and D. americana.

    Science.gov (United States)

    Sweigart, Andrea L

    2010-03-01

    Postzygotic reproductive isolation evolves when hybrid incompatibilities accumulate between diverging populations. Here, I examine the genetic basis of hybrid male sterility between two species of Drosophila, Drosophila virilis and D. americana. From these analyses, I reach several conclusions. First, neither species carries any autosomal dominant hybrid male sterility alleles: reciprocal F(1) hybrid males are perfectly fertile. Second, later generation (backcross and F(2)) hybrid male sterility between D. virilis and D. americana is not polygenic. In fact, I identified only three genetically independent incompatibilities that cause hybrid male sterility. Remarkably, each of these incompatibilities involves the Y chromosome. In one direction of the cross, the D. americana Y is incompatible with recessive D. virilis alleles at loci on chromosomes 2 and 5. In the other direction, the D. virilis Y chromosome causes hybrid male sterility in combination with recessive D. americana alleles at a single QTL on chromosome 5. Finally, in contrast with findings from other Drosophila species pairs, the X chromosome has only a modest effect on hybrid male sterility between D. virilis and D. americana.

  14. Compound Heterozygosity of Dominant and Recessive COL7A Alleles in a Severely Affected Patient with a Family History of Dystrophic Epidermolysis Bullosa: Clinical Findings, Genetic Testing, and Treatment Implications.

    Science.gov (United States)

    Watson, Kendra D; Schoch, Jennifer J; Beek, Geoffrey J; Hand, Jennifer L

    2017-03-01

    An 8-year-old girl born to a family with more than three generations of dominant dystrophic epidermolysis bullosa (DDEB) presented with life-threatening confluent skin erosions, mitten hand deformity, and failure to thrive. Reassessment of her family history and genetic testing showed compound heterozygous COL7A mutations, one inherited from her DDEB-affected mother and one from her unaffected, healthy father. This family illustrates the risk of unexpected, severe, autosomal recessive epidermolysis bullosa (EB) in a family with milder, multigenerational autosomal dominant EB. Clinicians should recognize the clinical spectrum of dystrophic EB and recommend genetic consultation when the phenotype conflicts with family history. © 2017 Wiley Periodicals, Inc.

  15. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease.

    Science.gov (United States)

    Ancliff, P J; Gale, R E; Liesner, R; Hann, I M; Linch, D C

    2001-11-01

    Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2 could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2 are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.

  16. A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series

    Directory of Open Access Journals (Sweden)

    Rashid Ban Mousa

    2013-01-01

    Full Text Available Abstract Introduction Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case presentation Case 1 is the 12-year-old daughter (index patient of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1, whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG located in exon 15 (c.1225C>T of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T. Case 2 is the 16-year-old son (brother of the index patient of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride

  17. A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series.

    Science.gov (United States)

    Rashid, Ban Mousa; Rashid, Nawshirwan Gafoor; Schulz, Ansgar; Lahr, Georgia; Nore, Beston Faiek

    2013-01-09

    Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case 1 is the 12-year-old daughter (index patient) of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1), whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T).Case 2 is the 16-year-old son (brother of the index patient) of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride channel 7 gene in this patient (Case 2). The missense

  18. Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

    Science.gov (United States)

    Schindler, Emily I; Nylen, Erik L; Ko, Audrey C; Affatigato, Louisa M; Heggen, Andrew C; Wang, Kai; Sheffield, Val C; Stone, Edwin M

    2010-10-01

    Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

  19. Enamel lesions in development, classification in Costa Rican families

    International Nuclear Information System (INIS)

    Murillo Knudsen, Gina; Berrocal Salazar, Cristina

    2013-01-01

    Enamel lesions in development were identified and classified in patients of Llano Grande de Cartago, examined at the Facultad de Odontologia of the Universidad de Costa Rica. A guide is provided over the topic. 15 children and 2 Costa Rican adults were selected. Clinical examinations, radiographs and clinical photographs were used as data collection method. Dental defects of the enamel were classified according to the possible genetic causes and without genetic causes. Imperfect Amelogenesis (IA) was diagnosed in 10 of patients. Hypoplastic IA was determined in 3 siblings with autosomal recessive inheritance, for 16% of the total sample. Hypomineralized IA was identified in an adult and two of his sons, with autosomal dominant inheritance. The remaining 4 cases of IA have been sporadic. Lesions of dental fluorosis were determined in the Horowitz index in 4 individuals, from 2 unrelated families. Other defects unspecified of the enamel or hypoplasias were found in 3 individuals. Enamel lesions in development should be classified with precision, for the purpose to inform to patients affected about their condition, origin, prognosis and appropriate treatment. The basis are established to implement reliability in the construction of family genealogy, identification and classification of enamel lesions, as well as the probabilities of future generations to express the lesions in the enamel of temporary or permanent dentition [es

  20. Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.

    Directory of Open Access Journals (Sweden)

    Stefano Lise

    Full Text Available β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5, an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1. In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome.

  1. Characterization of a new full length TMPRSS3 isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan

    Directory of Open Access Journals (Sweden)

    Shotland Lawrence I

    2004-09-01

    Full Text Available Abstract Background Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10. TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of TMPRSS3 in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of TMPRSS3. Methods We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis. DNA samples from participating individuals were sequenced for TMPRSS3. The structure of TMPRSS3 was characterized bioinformatically and experimentally by sequencing novel cDNA clones of TMPRSS3. Results We identified mutations in TMPRSS3 in four Pakistani families with recessive, nonsyndromic congenital deafness. We also identified two recessive mutations, one of which is novel, of TMPRSS3 segregating in a six-generation extended family from Newfoundland. The spectrum of TMPRSS3 mutations is reviewed in the context of a genotype-phenotype correlation. Our study also revealed a longer isoform of TMPRSS3 with a hitherto unidentified exon encoding a signal peptide, which is expressed in several tissues. Conclusion Mutations of TMPRSS3 contribute to hearing loss in many communities worldwide and account for 1.8% (8 of 449 of Pakistani families segregating congenital deafness as an autosomal recessive trait. The newly identified TMPRSS3 isoform e will be helpful in the functional characterization of the full length protein.

  2. Disease: H01880 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01880 Autosomal recessive microcephaly and chorioretinopathy Autosomal-recessive ...ent in MCCRP patients are variable, but the chorioretinopathy is a constant feature and includes typical pun...ark DB ... TITLE ... Chorioretinopathy with hereditary microcephaly. ... JOURNAL ... Arch Ophthalmol 75:597-600 (1... autosomal recessive microcephaly and chorioretinopathy. ... JOURNAL ... Eur J Hum Genet 24:1702-1706 (2016) DOI... ... Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy

  3. Amelogenesis imperfecta: A challenge to restoring esthetics and function

    Directory of Open Access Journals (Sweden)

    Ranganath V

    2010-01-01

    Full Text Available Rehabilitation of complicated cases poses difficulty in clinical practice, both with respect to restoring function and with esthetics. One such clinical condition where the dentist has to give importance to proper planning of the treatment and execution of the plan is amelogenesis imperfecta (AI, a condition where both function and esthetics are accommodated. This article discusses both the functional and esthetic rehabilitation of a patient with AI. Both the esthetics and function were hampered in this patient due to the condition. As a result, the treatment was properly planned and executed. A number of treatment options are available for us today to treat such a case. There is no one technique to be followed as such. However, the aim was to properly diagnose the case and provide good function and esthetics to the patient.

  4. Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

    DEFF Research Database (Denmark)

    2017-01-01

    The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients...... with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient-parent trios that were generally...... not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population....

  5. Al-Aqeel Sewairi Syndrome, a new autosomal recessive disorder with multicentric osteolysis, nodulosis and arthropathy. The first genetic defect of matrix metalloproteinase 2 gene

    International Nuclear Information System (INIS)

    Al-Aqeel, Aida I.

    2005-01-01

    We report a distinctive autosomal recessive multicentric osteolysis in Saudi Arabian families with distal arthropathy of the metacarpal, metatarsal and interphalangeal joints, with ultimate progression to the proximal joints with decreased range of movements and deformities with ankylosis and generalized osteopenia. In addition, they had large, painful to touch palmar and plantar pads. Hirsutism and mild dysmorphic facial features including proptosis, a narrow nasal bridge, bulbous nose and micrognathia. Using a genome-wide search for microsatellite markers from 11 members of the family from the Armed Forces Hospital and King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, localized the disease gene to chromosome 16q12-21. Haplotype analysis with additional markers narrowed the critical region to 1.2cM and identified the matrix metalloproteinase 2 (MMP-2), (gelatinase A, collagenase type IV, EC 3.4, 24,24) gene as a disease candidate at Mount Sinai School of Medicine, New York, United States of America in April 2000. Some affected individuals were homoallelic for a nonsense mutation (TCA>TAA) in codon 244 of exon 5, predicting the replacement of a tyrosine residue by a stop codon in the first fibronectin type II domain (Y244X). Other affected members had a missense mutation in exon 2 arginine 101-histidine (R101H) leading to no MMP-2 enzyme activity in serum or fibroblast or both of affected individuals. In other affected members, a non-pathogenic homoallelic GT transversion resulted in the substitution of an aspartate with a tyrosine residue in codon 210 of exon 4 (D210Y). The MMP-2-null mouse has no developmental defects, but are small, which may reflect genetic redundancy. The discovery that deficiency of this well-characterized gelatinase/collagenase results in an inherited form of an osteolytic and arthritic disorder provides an invaluable insights for the understanding of osteolysis and arthritis and is the first genetic

  6. Correction of malocclusion and oral rehabilitation in a case of amelogenesis imperfecta by insertion of dental implants followed by Le Fort I distraction osteogenesis of the edentulous atrophic maxilla.

    Science.gov (United States)

    Apaydin, Aysegul; Sermet, Bulent; Ureturk, Sevin; Kundakcioglu, Abdulsamet

    2014-09-17

    Amelogenesis imperfecta refers a group of hereditary diseases affecting the teeth and can present a variety of clinical forms and appearances, compromising esthetic appearance. Amelogenesis imperfecta variably reduces oral health quality and can result in severe psychological problems. We present the management of an amelogenesis imperfecta Angle class III malocclusion case with speech, esthetics and functional problems. This is an example of the rarely presented delayed eruption with multiple morphologic dental alterations and edentulous maxilla.There are only a few available reports in which this method is used method to correct sagittal discrepancies in edentulous patients.Our treatment plan consisted of a preoperative diagnostic and prosthodontics phase (including preparation of guiding prosthesis), followed by a surgical phase of Le Fort I osteotomy, distraction osteogenesis to correct the malocclusion, implant insertion and a follow up final restorative phase. Our treatment strategy attempts to serve patient needs, achieving function and esthetics while also minimizing the risk of reconstruction failure. Treatment not only restored function and esthetics, but also showed a positive psychological impact and thereby improved perceived quality of life.

  7. Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

    Science.gov (United States)

    Misgar, R A; Hassan, Z; Wani, A I; Bashir, M I

    2017-01-01

    Amelogenesis imperfecta (AI) is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA) have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

  8. Amelogenesis imperfecta with distal renal tubular acidosis: A novel syndrome?

    Directory of Open Access Journals (Sweden)

    R A Misgar

    2017-01-01

    Full Text Available Amelogenesis imperfecta (AI is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

  9. Hereditary sensory and autosomal peripheral neuropathy-type IV: case series and review of literature.

    Science.gov (United States)

    Ashwin, D P; Chandan, G D; Jasleen, Handa Kaur; Rajkumar, G C; Rudresh, K B; Prashanth, R

    2015-06-01

    Hereditary sensory and autonomic neuropathy (HSAN) IV is a rare autosomal recessive disorder which is characterized by a decrease in the number of myelinated and non-myelinated nerve fibers of peripheral nerves which causes diminished or absent pain sensation leading to increase in self-mutilative habits. A retrospective study of eight cases ranging from age group of 4 to 17 years for oral and digital signs and symptoms is presented. All the patients showed congenital insensitivity to pain and anhidrosis. Oral self-mutilations, such as autoextraction of teeth and severe bite injuries (with resultant scarring) of the finger tips and oral soft tissues (tongue, lip, and buccal mucosa) were found in most patients. Our study suggests that early diagnosis and specific treatment plan are important for prevention of characteristic of the oral as well as digital trauma associated with this disorder.

  10. Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects.

    Science.gov (United States)

    Rodríguez-Pazos, L; Ginarte, M; Fachal, L; Toribio, J; Carracedo, A; Vega, A

    2011-10-01

      Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations. We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods  We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  11. Blepharophimosis-mental retardation (BMR) syndromes: A proposed clinical classification of the so-called Ohdo syndrome, and delineation of two new BMR syndromes, one X-linked and one autosomal recessive.

    Science.gov (United States)

    Verloes, Alain; Bremond-Gignac, Dominique; Isidor, Bertrand; David, Albert; Baumann, Clarisse; Leroy, Marie-Anne; Stevens, René; Gillerot, Yves; Héron, Delphine; Héron, Bénédicte; Benzacken, Brigitte; Lacombe, Didier; Brunner, Han; Bitoun, Pierre

    2006-06-15

    We report on 11 patients from 8 families with a blepharophimosis and mental retardation syndrome (BMRS) phenotype. Using current nosology, five sporadic patients have Ohdo syndrome, associated with congenital hypothyroidism in two of them (thus also compatible with a diagnosis of Young-Simpson syndrome). In two affected sibs with milder phenotype, compensated hypothyroidism was demonstrated. In another family, an affected boy was born to the unaffected sister of a previously reported patient. Finally, in the last sibship, two affected boys in addition had severe microcephaly and neurological anomalies. A definitive clinical and etiologic classification of BMRS is lacking, but closer phenotypic analysis should lead to a more useful appraisal of the BMRS phenotype. We suggest discontinuing the systematic use of the term "Ohdo syndrome" when referring to patients with BMRS. We propose a classification of BMRS into five groups: (1) del(3p) syndrome, (possibly overlooked in older reports); (2) BMRS, Ohdo type, limited to the original patients of Ohdo; (3) BMRS SBBYS (Say-Barber/Biesecker/Young-Simpson) type, with distinctive dysmorphic features and inconstant anomalies including heart defect, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism. BMRS type SBBYS is probably an etiologically heterogeneous phenotype, as AD and apparently AR forms exist; (4) BMRS, MKB (Maat-Kievit-Brunner) type, with coarse, triangular face, which is probably sex-linked; (5) BMRS V (Verloes) type, a probable new type with severe microcephaly, hypsarrhythmia, adducted thumbs, cleft palate, and abnormal genitalia, which is likely autosomal recessive. Types MKB and V are newly described here. Copyright 2006 Wiley-Liss, Inc.

  12. Novel Presenting Phenotype in a Child With Autosomal Dominant Best's Vitelliform Macular Dystrophy.

    Science.gov (United States)

    Abdalla, Yasmine F; De Salvo, Gabriella; Elsahn, Ahmad; Self, James E

    2017-07-01

    Best's macular dystrophy (BMD) usually manifests with visual failure in the first or second decade of life; however, there is a large variability in expressivity of the disease, and some patients have no manifestation other than a pathological electro-oculogram (EOG). Autosomal dominant Best's vitelliform macular dystrophy (AD-BVMD) has a very specific phenotype that varies with the stage of the disease. In recent years, the authors have seen description of another clinical entity known as autosomal recessive BMD. Herein, the authors describe a 5-year-old girl referred from a peripheral hospital for investigation with a positive family history of BMD. Clinical findings included best-corrected visual acuity of 0.325 and 0.300 in the right and left eyes, respectively, by Sonksen logMar test, full color vision, normal orthoptic examination, and a small degree of hyperopia consistent with age. Macular optical coherence tomography (OCT) showed intraretinal fluid cysts and EOG showed reduced Arden ratio. Genetic testing was done for the proband and her father, who were found to be heterozygous for c.37C>T p. (Arg13Cys). The proband's younger sister will be reviewed and followed up once of age. The authors identified a new phenotype of AD-BVMD; although this is a single patient, more young children with BMD can now be scanned with the availability of hand-held OCT with better knowledge of the phenotype. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:580-585.]. Copyright 2017, SLACK Incorporated.

  13. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

    Science.gov (United States)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

    2011-11-01

    BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

  14. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

    Science.gov (United States)

    Lagier-Tourenne, Clotilde; Tazir, Meriem; López, Luis Carlos; Quinzii, Catarina M; Assoum, Mirna; Drouot, Nathalie; Busso, Cleverson; Makri, Samira; Ali-Pacha, Lamia; Benhassine, Traki; Anheim, Mathieu; Lynch, David R; Thibault, Christelle; Plewniak, Frédéric; Bianchetti, Laurent; Tranchant, Christine; Poch, Olivier; DiMauro, Salvatore; Mandel, Jean-Louis; Barros, Mario H; Hirano, Michio; Koenig, Michel

    2008-03-01

    Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ(10) deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ(10) in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production.

  15. EST Table: DC540266 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 dpe- ...

  16. EST Table: FS936166 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 fwgP ...

  17. EST Table: BY921544 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 ovS0 ...

  18. Autosomal dominant distal myopathy due to a novel ACTA1 mutation.

    Science.gov (United States)

    Liewluck, Teerin; Sorenson, Eric J; Walkiewicz, Magdalena A; Rumilla, Kandelaria M; Milone, Margherita

    2017-08-01

    Mutations in skeletal muscle α-actin 1-encoding gene (ACTA1) cause autosomal dominant or recessive myopathies with marked clinical and pathological heterogeneity. Patients typically develop generalized or limb-girdle pattern of weakness, but recently a family with scapuloperoneal myopathy was reported. We describe a father and 2 children with childhood-to-juvenile onset distal myopathy, carrying a novel dominant ACTA1 variant, c.757G>C (p.Gly253Arg). Father had delayed motor development and developed significant proximal weakness later in life; he was initially misdiagnosed as having spinal muscular atrophy based on electromyographic findings. His children had predominant anterior distal leg and finger extensor involvement. Nemaline rods were abundant on the daughter's biopsy, absent on the father's initial biopsy, and extremely rare on the father's subsequent biopsy a decade later. The father's second biopsy also showed myofibrillar pathology and rare fibers with actin filament aggregates. The present family expands the spectrum of actinopathy to include a distal myopathy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    2014-01-01

    BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...... this study, we recommend promoting recess physical activity through a combination of actions, addressing barriers within the natural, social, physical and organizational environment....

  20. EST Table: FS929848 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available DICTED: similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia...1| PREDICTED: similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 fwgP ...

  1. FAM20A mutations can cause enamel-renal syndrome (ERS.

    Directory of Open Access Journals (Sweden)

    Shih-Kai Wang

    Full Text Available Enamel-renal syndrome (ERS is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS, which closely resembles ERS except for the renal calcifications. We characterized three families with AIGFS and identified, in each case, recessive FAM20A mutations: family 1 (c.992G>A; g.63853G>A; p.Gly331Asp, family 2 (c.720-2A>G; g.62232A>G; p.Gln241_Arg271del, and family 3 (c.406C>T; g.50213C>T; p.Arg136* and c.1432C>T; g.68284C>T; p.Arg478*. Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to ERS. By characterizing teeth extracted from the family 3 proband, we demonstrated that FAM20A(-/- molars lacked true enamel, showed extensive crown and root resorption, hypercementosis, and partial replacement of resorbed mineral with bone or coalesced mineral spheres. Supported by the observation of severe ectopic calcifications in the kidneys of Fam20a null mice, we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes, and that mutations in FAM20A cause both AIGFS and ERS.

  2. The Great Recession was not so Great

    NARCIS (Netherlands)

    van Ours, J.C.

    2015-01-01

    The Great Recession is characterized by a GDP-decline that was unprecedented in the past decades. This paper discusses the implications of the Great Recession analyzing labor market data from 20 OECD countries. Comparing the Great Recession with the 1980s recession it is concluded that there is a

  3. Mutation analysis of SLC26A4 for Pendred syndrome and nonsyndromic hearing loss by high-resolution melting

    DEFF Research Database (Denmark)

    Chen, Neng; Tranebjærg, Lisbeth; Rendtorff, Nanna Dahl

    2011-01-01

    Pendred syndrome and DFNB4 (autosomal recessive nonsyndromic congenital deafness, locus 4) are associated with autosomal recessive congenital sensorineural hearing loss and mutations in the SLC26A4 gene. Extensive allelic heterogeneity, however, necessitates analysis of all exons and splice sites...

  4. Disease: H01204 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01204 Cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome (CA...MRQ) Cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome (CAMRQ) is autosomal recessive,... Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium

  5. LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS : A Severe Phenotype With Considerable Interindividual Variability

    NARCIS (Netherlands)

    Mathijssen, Inge B; Florijn, Ralph J; van den Born, L Ingeborgh; Zekveld-Vroon, Renate C; Ten Brink, Jacoline B; Plomp, Astrid S; Baas, Frank; Meijers-Heijboer, Hanne; Bergen, Arthur A B; van Schooneveld, Mary J

    2017-01-01

    PURPOSE: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. METHODS: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C;

  6. Mutational characterization of the P3H1/CRTAP/CypB complex in recessive osteogenesis imperfecta.

    Science.gov (United States)

    Barbirato, C; Trancozo, M; Almeida, M G; Almeida, L S; Santos, T O; Duarte, J C G; Rebouças, M R G O; Sipolatti, V; Nunes, V R R; Paula, F

    2015-12-03

    Osteogenesis imperfecta (OI) is a genetic disease characterized by bone deformities and fractures. Most cases are caused by autosomal dominant mutations in the type I collagen genes COL1A1 and COL1A2; however, an increasing number of recessive mutations in other genes have been reported. The LEPRE1, CRTAP, and PPIB genes encode proteins that form the P3H1/CRTAP/CypB complex, which is responsible for posttranslational modifications of type I collagen. In general, mutations in these genes lead to severe and lethal phenotypes of recessive OI. Here, we describe sixteen genetic variations detected in LEPRE1, CRTAP, and PPIB from 25 Brazilian patients with OI. Samples were screened for mutations on single-strand conformation polymorphism gels and variants were determined by automated sequencing. Seven variants were detected in patients but were absent in control samples. LEPRE1 contained the highest number of variants, including the previously described West African allele (c.1080+1G>T) found in one patient with severe OI as well as a previously undescribed p.Trp675Leu change that is predicted to be disease causing. In CRTAP, one patient carried the c.558A>G homozygous mutation, predicted as disease causing through alteration of a splice site. Genetic variations detected in the PPIB gene are probably not pathogenic due to their localization or because of their synonymous effect. This study enhances our knowledge about the mutational pattern of the LEPRE1, CRTAP, and PPIB genes. In addition, the results strengthen the proposition that LEPRE1 should be the first gene analyzed in mutation detection studies in patients with recessive OI.

  7. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.

    Science.gov (United States)

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-05-05

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.

  8. NCBI nr-aa BLAST: CBRC-FRUB-02-0208 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available y and hepatic disease 1 (autosomal recessive)-like 1 (PKHD1L1) [Danio rerio] emb|CAP09460.1| novel gene simi...lar to vertebrate polycystic kidney and hepatic disease 1 (autosomal recessive)-like 1 (PKHD1L1) [Danio rerio] CAP09515.1 1e-111 42% ...

  9. CT evaluation of the anterior epitympanic recess

    International Nuclear Information System (INIS)

    Yamasoba, Tatsuya; Kikuchi, Shigeru; Takeuchi, Naonobu; Harada, Takehiko; Nomura, Yasuya

    1991-01-01

    The structures of the anterior epitympanic recess and its surrounding tissues were examined among non-inflammatory ear, chronic otitis media with central perforation and cholesteatoma, using axial scans of high resolution computed tomography. The length and width of the recess, as well as the number of the slices where the cog was determined, had no significant differences among them. Thus, the bony structure of the recess was considered to be seldom influenced by inflammatory processes. In the non-inflammatory ear, the degree of pneumatization around the recess was similar to that of the petrous apex cells and lower than that of the mastoid cells. In the chronic otitis media with central perforation and cholesteatoma, the pneumatization of the whole temporal bones was suppressed and the tendency was also found that the cells around the recess were less pneumatized than the mastoid cells. When cholesteatoma invaded into the anterior epitympanic recess, the destruction of the bony protrusion of the lateral wall between the recess and the epitympanum was recognized, as well as the disappearance of the cog. The bony protrusion was considered to be an inferior extention of the cog toward the anterior tympanic spine. (author)

  10. Genetics Home Reference: autosomal recessive hypotrichosis

    Science.gov (United States)

    ... in the growth and division (proliferation) and maturation (differentiation) of cells within hair follicles . These cell processes ... LIPH , LPAR6 , or DSG4 gene result in the production of abnormal proteins that cannot aid in the ...

  11. Familial megacalyces with autosomal recessive inheritance

    International Nuclear Information System (INIS)

    Lam, A.H.

    1988-01-01

    Three children with bilateral congenital megacalyces from a consanguinous marriage are reported. No renal abnormality was detected in the parents. Our observation supports the genetic nature of the disease. The ultrasonographic features of congenital megacalyces are described. (orig.)

  12. Looking the cow in the eye: deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle.

    Science.gov (United States)

    Murgiano, Leonardo; Jagannathan, Vidhya; Calderoni, Valerio; Joechler, Monika; Gentile, Arcangelo; Drögemüller, Cord

    2014-01-01

    Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.

  13. Looking the Cow in the Eye: Deletion in the NID1 Gene Is Associated with Recessive Inherited Cataract in Romagnola Cattle

    Science.gov (United States)

    Murgiano, Leonardo; Jagannathan, Vidhya; Calderoni, Valerio; Joechler, Monika; Gentile, Arcangelo; Drögemüller, Cord

    2014-01-01

    Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract. PMID:25347398

  14. Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor.

    Science.gov (United States)

    Zheng, X; Goodwin, A F; Tian, H; Jheon, A H; Klein, O D

    2017-11-01

    The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration. Utilizing models of Ras dysregulation as well as inhibitors of the MAPK and PI3K pathways, we found that MAPK and PI3K regulate dental epithelial stem cell activity, transit-amplifying cell proliferation, and enamel formation in the mouse incisor.

  15. Autosomal dominant hereditary ataxia in Sri Lanka

    OpenAIRE

    Sumathipala, Dulika S; Abeysekera, Gayan S; Jayasekara, Rohan W; Tallaksen, Chantal ME; Dissanayake, Vajira HW

    2013-01-01

    Background Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. Methods ...

  16. Differences in Physical Activity during School Recess

    Science.gov (United States)

    Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer

    2011-01-01

    Background: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels. Methods: Two hundred and ten children (45% boys) from grades 3…

  17. A novel AMELX mutation causes hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Kim, Young-Jae; Kim, Youn Jung; Kang, Jenny; Shin, Teo Jeon; Hyun, Hong-Keun; Lee, Sang-Hoon; Lee, Zang Hee; Kim, Jung-Wook

    2017-04-01

    Amelogenesis imperfecta (AI) is a hereditary genetic defect affecting tooth enamel. AI is heterogeneous in clinical phenotype as well as in genetic etiology. To date, more than 10 genes have been associated with the etiology of AI. Amelogenin is the most abundant enamel matrix protein, most of which is encoded by the amelogenin gene in the X-chromosome (AMELX). More than 16 alternative splicing transcripts have been identified in the murine Amelx gene. The purpose of this study was to identify the genetic cause of an AI family. We recruited a family with hypoplastic AI and performed mutational analysis on the candidate gene based on the clinical phenotype. Mutational analysis revealed a missense mutation in exon 6 (NM_182680.1; c.242C > T), which changes a sequence in a highly conserved amino acid (NP_872621.1; p.Pro81Leu). Furthermore, a splicing assay using a minigene displayed that the mutation changed the mRNA splicing repertory. In this study, we identified a novel AMELX missense mutation causing hypoplastic AI, and this mutation also resulted in altered mRNA splicing. These results will not only expand the mutation spectrum causing AI but also broaden our understanding of the biological mechanism of enamel formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Modified adjustable suture hang-back recession: Description of technique and comparison with conventional adjustable hang-back recession

    Directory of Open Access Journals (Sweden)

    Siddharth Agrawal

    2017-01-01

    Full Text Available Purpose: This study aims to describe and compare modified hang-back recession with the conventional hang-back recession in large angle comitant exotropia (XT. Methods: A prospective, interventional, double-blinded, randomized study on adult patients (>18 years undergoing single eye recession-resection for large angle (>30 prism diopters constant comitant XT was conducted between January 2011 and December 2015. Patients in Group A underwent modified hang-back lateral rectus recession with adjustable knot while in Group B underwent conventional hang-back recession with an adjustable knot. Outcome parameters studied were readjustment rate, change in deviation at 6 weeks, complications and need for resurgery at 6 months. Results: The groups were comparable in terms of age and preoperative deviation. The patients with the modified hang back (Group A fared significantly better (P < 0.05 than those with conventional hang back (Group B in terms of lesser need for adjustment, greater correction in deviation at 6 weeks and lesser need for resurgery at 6 months. Conclusion: This modification offers several advantages, significantly reduces resurgery requirement and has no added complications.

  19. Gingival recession: a cross-sectional clinical investigation.

    Science.gov (United States)

    Goutoudi, P; Koidis, P T; Konstantinidis, A

    1997-06-01

    In this cross-sectional study, risk and potentially causative factors of gingival recession were examined and their relationship to apical migration of the gingival margin evaluated. Thirty eight patients (18-60 years), displaying one or more sites with gingival recession but without any significant periodontal disease participated. A total of 28 parameters were evaluated in both 'test' teeth (50 teeth with gingival recession) and 'control' teeth (50 contralateral teeth). The results revealed that gingival margin recession was associated with both high inflammatory and plaque scores, with decreased widths of keratinized and attached gingiva and with the subjects' toothbrush bristle hardness.

  20. HYDRORECESSION: A toolbox for streamflow recession analysis

    Science.gov (United States)

    Arciniega, S.

    2015-12-01

    Streamflow recession curves are hydrological signatures allowing to study the relationship between groundwater storage and baseflow and/or low flows at the catchment scale. Recent studies have showed that streamflow recession analysis can be quite sensitive to the combination of different models, extraction techniques and parameter estimation methods. In order to better characterize streamflow recession curves, new methodologies combining multiple approaches have been recommended. The HYDRORECESSION toolbox, presented here, is a Matlab graphical user interface developed to analyse streamflow recession time series with the support of different tools allowing to parameterize linear and nonlinear storage-outflow relationships through four of the most useful recession models (Maillet, Boussinesq, Coutagne and Wittenberg). The toolbox includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error) and three different methods to extract hydrograph recessions segments (Vogel, Brutsaert and Aksoy). In addition, the toolbox has a module that separates the baseflow component from the observed hydrograph using the inverse reservoir algorithm. Potential applications provided by HYDRORECESSION include model parameter analysis, hydrological regionalization and classification, baseflow index estimates, catchment-scale recharge and low-flows modelling, among others. HYDRORECESSION is freely available for non-commercial and academic purposes.

  1. Performance Analysis of High-Speed Deep/Shallow Recessed Hybrid Bearing

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2013-01-01

    Full Text Available The present paper proposes a theoretical analysis of the performance of deep/shallow recessed hybrid bearing. It is intended that, on the basis of the numerical results drawn from this study, appropriate shallow recess depth and width can be determined for use in the bearing design process. By adopting bulk flow theory, the turbulent Reynolds equation and energy equation are modified and solved numerically including concentrated inertia effects at the recess edge with different depth and width of shallow recess. The results indicate that the load capacity, drag torque increases as the depth of shallow recess is shallower and the width ratio (half angle of deep recess versus half angle of shallow recess is smaller. In contrast, the flow rate decreases as the depth of shallow recess is shallower and the width ratio is smaller. Nevertheless, the appropriate design of the depth and width of shallow recess might well induce the performance of high-speed deep/shallow recessed hybrid bearing.

  2. Prognostic Indicators of Gingival Recession in Nigeria: Preliminary Findings

    Directory of Open Access Journals (Sweden)

    Michael Adedigba

    2010-06-01

    Full Text Available AIM: Literature is replete with studies on gingival recession, the apical shift of the gingival margin from the cemento-enamel junction. Chronic periodontitis and frequent toothbrushing are among its aetiological factors. Many of these were however prevalence studies. The current study was therefore aimed at separating prognostic indicators from determinants of the number of recessions. METHOD: 650 consecutive adult patients visiting a Nigerian teaching hospital were examined using a checklist including plaque, calculus, Miller’s class of recession and other parameters.. A total of 408 recession sites were identified. RESULTS: The mean age of the patients with recession was 42.3 years; mean number of recession was 4.74 Incisors had the highest number of recessions (35.7%. While a factor such as age was related both to the number and prognosis of recession sites, abrasion and plaque were only related to prognosis. Again, some of the factors previously significantly related to prognosis on univariate analysis like calculus and smoking, lost their significance on regression analysis. CONCLUSION: The three strongest predictors of prognosis (Miller’s class of recession were age, plaque and abrasion. [TAF Prev Med Bull 2010; 9(3.000: 187-194

  3. Tricho-Dento-Osseous Syndrome: Diagnosis and Dental Management

    Directory of Open Access Journals (Sweden)

    Ola B. Al-Batayneh

    2012-01-01

    Full Text Available Tricho-dento-osseous (TDO syndrome is a rare, autosomal dominant disorder principally characterised by curly hair at infancy, severe enamel hypomineralization and hypoplasia and taurodontism of teeth, sclerotic bone, and other defects. Diagnostic criteria are based on the generalized enamel defects, severe taurodontism especially of the mandibular first permanent molars, an autosomal dominant mode of inheritance, and at least one of the other features (i.e., nail defects, bone sclerosis, and curly, kinky or wavy hair present at a young age that may straighten out later. Confusion with amelogenesis imperfecta is common; however, taurodontism is not a constant feature of any of the types of amelogenesis imperfecta. Management of TDO requires a team approach, proper documentation, and a long-term treatment and follow-up plan. The aim of treatment is to prevent problems such as sensitivity, caries, dental abscesses, and loss of occlusal vertical dimension through attrition of hypoplastic tooth structure. Another aim is to restore function of the dentition and enhance the esthetics and self-esteem of the patient. This paper proposes treatment approaches that include preventive, restorative, endodontic, prosthetic, and surgical options to management. In addition, it sheds light on the difficulties faced during dental treatment of such cases.

  4. The Great Recession and America's Geography of Unemployment.

    Science.gov (United States)

    Thiede, Brian C; Monnat, Shannon M

    The Great Recession of 2007-2009 was the most severe and lengthy economic crisis in the U.S. since the Great Depression. The impacts on the population were multi-dimensional, but operated largely through local labor markets. To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. The local consequences of macroeconomic trends are associated with county population characteristics, as well as the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state inequality between local labor market conditions. To present new estimates of the recession's impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately large recession-related increases in unemployment.

  5. Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations.

    Science.gov (United States)

    Yamaguti, Paulo Marcio; Neves, Francisco de Assis Rocha; Hotton, Dominique; Bardet, Claire; de La Dure-Molla, Muriel; Castro, Luiz Claudio; Scher, Maria do Carmo; Barbosa, Maristela Estevão; Ditsch, Christophe; Fricain, Jean-Christophe; de La Faille, Renaud; Figueres, Marie-Lucile; Vargas-Poussou, Rosa; Houillier, Pascal; Chaussain, Catherine; Babajko, Sylvie; Berdal, Ariane; Acevedo, Ana Carolina

    2017-01-01

    Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control the paracellular passage of calcium and magnesium. FHHNC can be linked to mutations in both genes. Claudin-16 was shown to be expressed during amelogenesis; however, no data are available on claudin-19. Moreover, the enamel phenotype of patients with CLDN19 mutations has never been described. In this study, we describe the clinical and genetic features of nine patients with FHHNC carrying CLDN19 mutations and the claudin-19 expression profile in rat ameloblasts. Six FHHNC Brazilian patients were subjected to mutational analysis. Three additional French patients were recruited for orodental characterisation. The expression profile of claudin-19 was evaluated by RT-qPCR and immunofluorescence using enamel epithelium from rat incisors. All patients presented AI at different degrees of severity. Two new likely pathogenic variations in CLDN19 were found: p.Arg200Gln and p.Leu90Arg. RT-qPCR revealed low Cldn19 expression in ameloblasts. Confocal analysis indicated that claudin-19 was immunolocalised at the distal poles of secretory and maturing ameloblasts. For the first time, it was demonstrated that AI is associated with FHHNC in patients carrying CLDN19 mutations. The data suggest claudin-19 as an additional determinant in enamel formation. Indeed, the coexistence of hypoplastic and hypomineralised AI in the patients was consistent with claudin-19 expression in both secretory and maturation stages. Additional indirect systemic effects cannot be excluded. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Three novel GJB2 (connexin 26) variants associated with autosomal dominant syndromic and nonsyndromic hearing loss.

    Science.gov (United States)

    DeMille, Desiree; Carlston, Colleen M; Tam, Oliver H; Palumbos, Janice C; Stalker, Heather J; Mao, Rong; Zori, Roberto T; Viskochil, David H; Park, Albert H; Carey, John C

    2018-04-01

    Connexin 26 (Cx26), encoded by the GJB2 gene, is a key protein involved in the formation of gap junctions in epithelial organs including the inner ear and palmoplantar epidermis. Pathogenic variants in GJB2 are responsible for approximately 50% of inherited sensorineural deafness. The majority of these variants are associated with autosomal recessive inheritance; however, rare reports of dominantly co-segregating variants have been published. Since we began offering GJB2 testing in 2003, only about 2% of detected GJB2 variants from our laboratory have been classified as dominant. Here we report three novel dominant GJB2 variants (p.Thr55Ala, p.Gln57_Pro58delinsHisSer, and p.Trp44Gly); two associated with syndromic sensorineural hearing loss and one with nonsyndromic hearing loss. In the kindred with the p.Thr55Ala variant, the proband and his father present with only leukonychia as a cutaneous finding of their syndromic hearing loss. This phenotype has been previously documented in conjunction with palmoplantar hyperkeratosis, but isolated leukonychia is a novel finding likely associated with the unique threonine to alanine change at codon 55 (other variants at this codon have been reported in cases of nonsyndromic hearing loss). This report contributes to the short list of GJB2 variants associated with autosomal dominant hearing loss, highlights the variability of skin and nail findings associated with such cases, and illustrates the occurrence of both syndromic and nonsyndromic presentations with changes in the same gene. © 2018 Wiley Periodicals, Inc.

  7. Disease: H00214 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00214 Hypophosphatemic rickets, including: X-Linked dominant hypophosphatemia (XL...H); X-Linked recessive hypophosphatemia (XLRH); Autosomal dominant hypophosphatemic rickets (ADHR); Autosoma...l recessive hypophosphatemic rickets (ARHR); Hereditary hypophophatemic rickets with hypercalciuria (HHRH) Hypophosphataemic rickets..., also known as vitamin D resistant rickets, is a group o...ulting in hypophosphatemia and rickets associated with mineralization defect. Fibroblast growth factor-23 (F

  8. Estimation of the frequency of occult mutations for an autosomal recessive disease in the presence of genetic heterogeneity: application to genetic hearing loss disorders.

    Science.gov (United States)

    Kimberling, William J

    2005-11-01

    The routine testing for pathologic mutation(s) in a patient's DNA has become the foundation of modern molecular genetic diagnosis. It is especially valuable when the phenotype shows genetic heterogeneity, and its importance will grow as treatments become genotype specific. However, the technology of mutation detection is imperfect and mutations are often missed. This can be especially troublesome when dealing with a recessive disorder where the combination of genetic heterogeneity and missed mutation creates an imprecision in the genotypic assessment of individuals who do not appear to have the expected complement of two pathologic mutations. This article describes a statistical approach to the estimation of the likelihood of a genetic diagnosis under these conditions. In addition to providing a means of testing for missed mutations, it also provides a method of estimating and testing for the presence of genetic heterogeneity in the absence of linkage data. Gene frequencies as well as estimates of sensitivity and specificity can be obtained as well. The test is applied to GJB2 recessive nonsyndromic deafness, Usher syndrome types Ib and IIa, and Pendred-enlarged vestibular aqueduct syndrome. Copyright 2005 Wiley-Liss, Inc.

  9. The Great Recession and America's geography of unemployment

    Directory of Open Access Journals (Sweden)

    Brian Thiede

    2016-09-01

    Full Text Available Background: The Great Recession of 2007-2009 was the most severe and lengthy economic crisis in the US since the Great Depression of the 1930s. The impacts on the population were multi-dimensional, but operated largely through local labor markets. Objective: To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. Methods: We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. Results: The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. Conclusions: The local consequences of macroeconomic trends are associated with county population characteristics, and the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state disparities in local labor market conditions. Contribution: To present new estimates of the recession's impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately

  10. Recessive Dystrophic Epidermolysis Bullosa and Pregnancy.

    Science.gov (United States)

    Boria, F; Maseda, R; Martín-Cameán, M; De la Calle, M; de Lucas, R

    2017-12-01

    Dystrophic epidermolysis bullosa is a rare inherited disease caused by mutations in the COL7A1 gene. Its recessive variant (recessive dystrophic epidermolysis bullosa) is characterized by the absence or considerably reduced expression of type VII collagen, which leads to marked fragility of the skin and mucous membranes and subsequent blister formation, whether spontaneously or following minimal injury. There have been very few reports of this disease in pregnant women. We present 2 cases of pregnant women with recessive dystrophic epidermolysis bullosa managed in our High-Risk Pregnancy Unit at Hospital Universitario La Paz, Madrid, Spain. Both patients underwent full-term cesarean delivery, with no further complications for mother or child. Although recessive dystrophic epidermolysis bullosa increases the risk of maternal complications, a patient is not advised against pregnancy. With adequate monitoring, these patients can fulfil their desire to become mothers. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Bond return predictability in expansions and recessions

    DEFF Research Database (Denmark)

    Engsted, Tom; Møller, Stig Vinther; Jensen, Magnus David Sander

    We document that over the period 1953-2011 US bond returns are predictable in expansionary periods but unpredictable during recessions. This result holds in both in-sample and out-of-sample analyses and using both univariate regressions and combination forecasting techniques. A simulation study...... but negative in recessions. The results are also consistent with tests showing that the expectations hypothesis of the term structure holds in recessions but not in expansions. However, the results for bonds are in sharp contrast to results for stocks showing that stock returns are predictable in recessions...... but not in expansions. Thus, our results indicate that there is not a common predictive pattern of stock and bond returns associated with the state of the economy....

  12. Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis

    DEFF Research Database (Denmark)

    Siemiatkowska, Anna M; van den Born, L Ingeborgh; van Genderen, Maria M

    2014-01-01

    , were screened in 532 additional patients with retinal dystrophies. This cohort encompassed 108 persons with isolated or autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well as 104 persons with LCA...... and associated phenotypes in different types of inherited retinal dystrophies. METHODS: DNA samples of 161 patients with LCA without genetic diagnosis were analyzed for variants in NMNAT1 using Sanger sequencing. Variants in exon 5 of NMNAT1, which harbors the majority of the previously identified mutations...

  13. MMP20 Promotes a Smooth Enamel Surface, a Strong DEJ, and a Decussating Enamel Rod Pattern

    Science.gov (United States)

    Bartlett, John D.; Skobe, Ziedonis; Nanci, Antonio; Smith, Charles E.

    2012-01-01

    Mutations of the Matrix metalloproteinase-20 (MMP20, enamelysin) gene cause autosomal recessive amelogenesis imperfecta and Mmp20 ablated mice also have malformed dental enamel. Here we show that Mmp20 null mouse secretory stage ameloblasts maintained a columnar shape and were present as a single layer of cells. However, the null maturation stage ameloblasts covered extraneous nodules of ectopic calcified material formed at the enamel surface. Remarkably, nodule formation occurs in null mouse enamel when MMP20 is normally no longer expressed. The malformed enamel in Mmp20 null teeth was loosely attached to the dentin and the entire enamel layer tended to separate from the dentin indicative of a faulty DEJ. The enamel rod pattern was also altered in Mmp20 null mice. Each enamel rod is formed by a single ameloblast and is a mineralized record of the migration path of the ameloblast that formed it. The Mmp20 null mouse enamel rods were grossly malformed or were absent indicating that the ameloblasts do not migrate properly when backing away from the DEJ. Thus, MMP20 is required for ameloblast cell movement necessary to form the decussating enamel rod patterns, for the prevention of ectopic mineral formation, and to maintain a functional DEJ. PMID:22243247

  14. Gingival Recessions and Biomechanics

    DEFF Research Database (Denmark)

    Laursen, Morten Godtfredsen

    Gingival recessions and biomechanics “Tissue is the issue, but bone sets the tone.“ A tooth outside the cortical plate can result in loss of bone and development of a gingival recession. The presentation aims to show biomechanical considerations in relation to movement of teeth with gingival...... by moving the root back in the alveolus. The tooth movement is accompanied by bone gain and thus increase the success rate for soft tissue augmentation. The choice of biomechanical system influences the treatment outcome. If a standard straight wire appliance is used, a biomechanical dilemma can arise...

  15. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome.

    Science.gov (United States)

    Burrage, Lindsay C; Charng, Wu-Lin; Eldomery, Mohammad K; Willer, Jason R; Davis, Erica E; Lugtenberg, Dorien; Zhu, Wenmiao; Leduc, Magalie S; Akdemir, Zeynep C; Azamian, Mahshid; Zapata, Gladys; Hernandez, Patricia P; Schoots, Jeroen; de Munnik, Sonja A; Roepman, Ronald; Pearring, Jillian N; Jhangiani, Shalini; Katsanis, Nicholas; Vissers, Lisenka E L M; Brunner, Han G; Beaudet, Arthur L; Rosenfeld, Jill A; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Xia, Fan; Lalani, Seema R; Lupski, James R; Bongers, Ernie M H F; Yang, Yaping

    2015-12-03

    Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. American undergraduate students' value development during the Great Recession.

    Science.gov (United States)

    Park, Heejung; Twenge, Jean M; Greenfield, Patricia M

    2017-02-01

    The Great Recession's influence on American undergraduate students' values was examined, testing Greenfield's and Kasser's theories concerning value development during economic downturns. Study 1 utilised aggregate-level data to investigate (a) population-level value changes between the pre-recession (2004-2006: n = 824,603) and recession freshman cohort (2008-2010: n = 662,262) and (b) overall associations of population-level values with national economic climates over long-term periods by correlating unemployment rates and concurrent aggregate-level values across 1966-2015 (n = 10 million). Study 2 examined individual-level longitudinal value development from freshman to senior year, and whether the developmental trajectories differed between those who completed undergraduate education before the Great Recession (freshmen in 2002, n = 12,792) versus those who encountered the Great Recession during undergraduate years (freshmen in 2006, n = 13,358). Results suggest American undergraduate students' increased communitarianism (supporting Greenfield) and materialism (supporting Kasser) during the Great Recession. The recession also appears to have slowed university students' development of positive self-views. Results contribute to the limited literature on the Great Recession's influence on young people's values. They also offer theoretical and practical implications, as values of this privileged group of young adults are important shapers of societal values, decisions, and policies. © 2016 International Union of Psychological Science.

  17. Bimedial faden recession versus augmented medial rectus recession in the treatment of high ac/a ratio partially accommodative esotropia with large distant near disparity

    Directory of Open Access Journals (Sweden)

    Mohammed F Farid

    2016-01-01

    Faden recession achieves marginal superior control of DND and high AC/A ratio in convergence excess partially accommodative ET. Augmented recession also works well with the possible development of consecutive exotropia in cases with extremely high DND. This study recommends Augmented recession for cases with mild to moderate DND and Faden recession for cases with extremely large DND.

  18. Autosomal dominant adult neuronal ceroid lipofuscinosis

    NARCIS (Netherlands)

    Nijssen, Peter C.G.

    2011-01-01

    this thesis investigates a family with autosomal dominant neuronal ceroid lipofuscinosis, with chapters on clinical neurology, neuropathology, neurogenetics, neurophysiology, auditory and visual aspects.

  19. Genetics Home Reference: dyskeratosis congenita

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. When dyskeratosis congenita is caused by mutations in other genes, it can be inherited in an autosomal dominant or autosomal recessive pattern. Autosomal dominant means one ...

  20. The Great Recession and Workers' Health Benefits.

    Science.gov (United States)

    Koh, Kanghyock

    2018-03-01

    During a recession, cost-sharing of employer-sponsored health benefits could increase to reduce labor costs in the U.S. Using a variation in the severity of recession shocks across industries, I find evidence that the enrollment rate of high deductible health plans (HDHPs) among workers covered by employer-sponsored health benefits increased more among firms in industries that experienced severe recession shocks. As potential mechanisms, I study employer-side and worker-side mechanisms. I find that employers changed health benefit offerings to force or incentivize workers to enroll in HDHPs. But I find little evidence of an increase in workers' demand for HDHPs due to a reduction in income. These results suggest that the HDHP enrollment rate increased during the Great Recession, as employers tried to save costs of offering health benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Measurement of the lateral recess angle as a possible alternative for evaluation of the lateral recess stenosis on a CT scan

    International Nuclear Information System (INIS)

    Strojnik, T.

    2001-01-01

    Stenosis of the lateral recess in the lumbar spinal canal is a clinical problem, especially in terms of surgical management. Criteria for the diagnosis and surgical treatment of lateral recess stenosis (LRS) are not clearly defined. Several authors have suggested measurement of the lateral recess height (LRH) on computed tomography (CT) scans as a helpful tool for making decisions in regard of management. The present study is based an the assumption that measurement of the lateral recess angle (LRA) may be useful in the clinical management of lateral recess stenosis. The reliability and significance of the results have been analyzed. In 35 patients, the stenosis was confirmed by intraoperative measurement of the lateral recess height. Fifty-three affected lateral recesses were analyzed. Before surgery, the heights on CT scans were measured. The mean value was 3.3 mm (SD = 0.9 mm), while 41 of them were 3.6 mm or less. Furthermore, the angles on CT scans were evaluated. The mean value was 25.9 degrees (SD = 4.9 degrees), 48 of them were 30 degrees or less and only 5 of them achieved more than 30 degrees. Results reveal that the best quantitative determination of a lateral recess stenosis is a CT scan angle measurement with a critical value of 30 degrees. A CT scan height of 3.6 mm or less is also indicative of stenosis. Statistical evaluation of the data by multiple regression analysis revealed agreement between intraoperative findings and measured heights (p = 0.02), while even better results were noted for angles (p < 0.01). Interfacet distance (IF) was found to be least predictive (p = 0.04). (author)

  2. Recessed floating pier caps for highway bridges.

    Science.gov (United States)

    1973-01-01

    Presented are alternate designs for two existing bridges in Virginia - one with steel beams and the other with prestressed concrete beams - whereby the pier caps are recessed within the depth of the longitudinal beams. The purpose of this recession i...

  3. Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy.

    Directory of Open Access Journals (Sweden)

    Cécile Méjécase

    Full Text Available GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying progressive inherited retinal disorders, by targeted next generation sequencing, a 32 year-old male sporadic case with severe rod-cone dystrophy and his unaffected parents were investigated by whole exome sequencing. This led to the identification of a homozygous nonsense variant, c.963C>A p.(Cys321* in GNAT1, which was confirmed by Sanger sequencing. The mother was heterozygous for this variant whereas the variant was absent in the father. c.963C>A p.(Cys321* is predicted to produce a shorter protein that lacks critical sites for the phototransduction cascade. Our work confirms that the phenotype and the mode of inheritance associated with GNAT1 variants can vary from autosomal dominant, autosomal recessive congenital stationary night blindness to autosomal recessive rod-cone dystrophy.

  4. Genetic dissection of hybrid incompatibilities between Drosophila simulans and D. mauritiana. I. Differential accumulation of hybrid male sterility effects on the X and autosomes.

    Science.gov (United States)

    Tao, Yun; Chen, Sining; Hartl, Daniel L; Laurie, Cathy C

    2003-08-01

    The genetic basis of hybrid incompatibility in crosses between Drosophila mauritiana and D. simulans was investigated to gain insight into the evolutionary mechanisms of speciation. In this study, segments of the D. mauritiana third chromosome were introgressed into a D. simulans genetic background and tested as homozygotes for viability, male fertility, and female fertility. The entire third chromosome was covered with partially overlapping segments. Many segments were male sterile, while none were female sterile or lethal, confirming previous reports of the rapid evolution of hybrid male sterility (HMS). A statistical model was developed to quantify the HMS accumulation. In comparison with previous work on the X chromosome, we estimate that the X has approximately 2.5 times the density of HMS factors as the autosomes. We also estimate that the whole genome contains approximately 15 HMS "equivalents"-i.e., 15 times the minimum number of incompatibility factors necessary to cause complete sterility. Although some caveats for the quantitative estimate of a 2.5-fold density difference are described, this study supports the notion that the X chromosome plays a special role in the evolution of reproductive isolation. Possible mechanisms of a "large X" effect include selective fixation of new mutations that are recessive or partially recessive and the evolution of sex-ratio distortion systems.

  5. Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    ... NIH Director Organization Budget History NIH Almanac Public Involvement Outreach & Education Visitor Information RePORT NIH Fact Sheets Home > Autosomal ... other than the observation that 50 percent of children born to an affected parent would develop the disease. Diagnosis of well-established ...

  6. Clinical spectrum of early onset cerebellar ataxia with retained tendon reflexes: an autosomal recessive ataxia not to be missed Espectro clínico da ataxia cerebelar de início precoce com reflexos mantidos: uma ataxia autossômica recessiva para não ser esquecida

    Directory of Open Access Journals (Sweden)

    José Luiz Pedroso

    2013-06-01

    Full Text Available Autosomal recessive cerebellar ataxias are a heterogeneous group of neurological disorders. In 1981, a neurological entity comprised by early onset progressive cerebellar ataxia, dysarthria, pyramidal weakness of the limbs and retained or increased upper limb reflexes and knee jerks was described. This disorder is known as early onset cerebellar ataxia with retained tendon reflexes. In this article, we aimed to call attention for the diagnosis of early onset cerebellar ataxia with retained tendon reflexes as the second most common cause of autosomal recessive cerebellar ataxias, after Friedreich ataxia, and also to perform a clinical spectrum study of this syndrome. In this data, 12 patients from different families met all clinical features for early onset cerebellar ataxia with retained tendon reflexes. Dysarthria and cerebellar atrophy were the most common features in our sample. It is uncertain, however, whether early onset cerebellar ataxia with retained tendon reflexes is a homogeneous disease or a group of phenotypically similar syndromes represented by different genetic entities. Further molecular studies are required to provide definitive answers to the questions that remain regarding early onset cerebellar ataxia with retained tendon reflexes.As ataxias cerebelares autossômicas recessivas são um grupo heterogêneo de doenças neurológicas. Em 1981, foi descrita uma entidade neurológica incluindo ataxia cerebelar progressiva de início precoce, disartria, liberação piramidal e manutenção ou aumento dos reflexos tendíneos nos membros superiores e inferiores. Essa síndrome é conhecida como ataxia cerebelar de início precoce com reflexos mantidos. Neste artigo, o objetivo foi chamar a atenção para o diagnóstico de ataxia cerebelar de início precoce com reflexos mantidos como a segunda causa mais comum de ataxia cerebelar autossômica recessiva, após a ataxia de Friedreich, e também realizar um estudo do espectro cl

  7. Genetics Home Reference: autosomal recessive primary microcephaly

    Science.gov (United States)

    ... microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet. 2005 May;76( ... genome editing and CRISPR-Cas9? What is precision medicine? What is newborn screening? New Pages Alopecia areata ...

  8. The First Survey of Distribution of Inherited Deafness Patterns in Individuals Referred to Genetic Center of Ahvaz Welfare Organization, Southern Iran

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohammadian

    2011-09-01

    Full Text Available Background and Aim: Deafness is a heterogeneous disorder induced by genetic and environmental factors. It is the most common hereditary sensory-neural disorder that affects 1/1000 to 1/2000 of the newborns. More than 70% of hearing loss cases are caused by genetic disorders, 85% of which result from nonsyndromic autosomal recessive sensory-neural hearing loss. Up to now, more than 100 genes contributing in hearing loss have been determined. Alteration of these genes may result in hearing loss.This study was performed to identify the inheritance patterns of deafness and its relation with ethnicity, gender and consanguineous marriages.Methods: In this survey, data from 356 families affected by hearing loss and referred to welfare organization of Ahvaz during the time were collected based on sex, ethnic groups and relativeness.Results: The results state a high frequency of autosomal recessive deafness caused by consanguineous marriages within Arab and non-Arab ethnic groups (p<0.05. But no significant difference in gender."nConclusion: In conclusion, the high frequency of autosomal recessive deafness among the population with a high frequency of consanguineous marriages is considerable. The dominant pattern of deafness observed in this population was autosomal recessive.

  9. Hospital Capital Investment During the Great Recession.

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal.

  10. Hospital Capital Investment During the Great Recession

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal. PMID:28617202

  11. Comparison of results of medial rectus muscle recession using augmentation, Faden procedure, and slanted recession in the treatment of high accommodative convergence/accommodation ratio esotropia.

    Science.gov (United States)

    Gharabaghi, Davoud; Zanjani, Leila Kazemi

    2006-01-01

    According to the literature, accommodative esotropia has an unpredictable course when nonsurgical treatment is considered, especially in cases with a high accommodative convergence/accommodation ratio (AC/A). The aim of this study was to compare the results of augmented recession, slanted recession, and recession with posterior fixation suture of the medial rectus muscles in the treatment of high AC/A esotropia. Twenty-eight children (4 to 14 years old) with high AC/A esotropia with a near-distance disparity greater than 10 PD were included in a prospective, randomized, blinded clinical trial. Nine children underwent recession of both medial rectus muscles and posterior fixation suture (Faden procedure), 9 children underwent augmented recession of the medial rectus muscles, and 10 children underwent slanted recession of both medial rectus muscles. The amount of esodeviation was measured before strabismus surgery and at least 6 months postoperatively. In the augmented recession group, the mean near-distance disparity was reduced from 16.33 +/- 2.17 PD preoperatively to 7.55 +/- 3.87 PD postoperatively (54.21%; P = .056). In the Faden procedure group, it was reduced from 15.22 +/- 4.08 PD to 2.55 +/- 4.03 PD (80.7%; P = .056). In the slanted recession group, it was reduced from 15.50 +/- 4.30 PD to 4.10 +/- 4.80 PD (67.55%; P = .056). The Faden procedure had the best outcome, but slanted recession also was successful. Because of our good results and an easy, non-invasive approach without any additional complications, we recommend slanted recession to treat high AC/A esotropia.

  12. Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect.

    Science.gov (United States)

    Barashkov, Nikolay A; Dzhemileva, Lilya U; Fedorova, Sardana A; Teryutin, Fedor M; Posukh, Olga L; Fedotova, Elvira E; Lobov, Simeon L; Khusnutdinova, Elza K

    2011-09-01

    Hereditary forms of hearing impairment (HI) caused by GJB2 (Cx26) mutations are the frequent sensory disorders registered among newborns in various human populations. In this study, we present data on the molecular, audiological and population features of autosomal recessive deafness 1A (DFNB1A) associated with the donor splicing site IVS1+1G>A mutation of GJB2 gene in Yakut population isolate of the Sakha Republic (Yakutia) located in Eastern Siberia (Russian Federation). The Yakut population exhibits high frequency of some Mendelian disorders, which are rare in other populations worldwide. Mutational analysis of GJB2 gene in 86 unrelated Yakut patients with congenital HI without other clinical features has been performed. In this study, we registered a large cohort of Yakut patients homozygous for the IVS1+1G>A mutation (70 unrelated deaf subjects in total). Detailed audiological analysis of 40 deaf subjects with genotype IVS1+1G>A/IVS1+1G>A revealed significant association of this genotype with mostly symmetrical bilateral severe to profound HI (85% severe-to-profound HI versus 15% mild-to-moderate HI, PA mutation (11.7%) has been found in Yakut population. Reconstruction of 140 haplotypes with IVS1+1G>A mutation demonstrates the common origin of all mutant chromosomes found in Yakuts. The age of mutation was estimated to be approximately 800 years. These findings characterize Eastern Siberia as the region with the most extensive accumulation of the IVS1+1G>A mutation in the world as a result of founder effect.

  13. Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth.

    Science.gov (United States)

    Li, Li-Li; Liu, Pei-Hong; Xie, Xiao-Hua; Ma, Su; Liu, Chao; Chen, Li; Qin, Chun-Lin

    2016-06-30

    FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20A(flox/flox) mice, we created K14-Cre;Fam20A(flox/flox) (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

  14. The specific role of FAM20C in amelogenesis.

    Science.gov (United States)

    Wang, X; Jung, J; Liu, Y; Yuan, B; Lu, Y; Feng, J Q; Qin, C

    2013-11-01

    Previously, we showed that Sox2-Cre;Fam20C(fl/fl) mice in which Fam20C was ubiquitously inactivated had severe defects in dentin, enamel, and bone, along with hypophosphatemia. It remains to be determined if the enamel defects in the mice with universal inactivation of Family with sequence similarity 20-C (FAM20C) were associated with the dentin defects and whether hypophosphatemia in the knockout mice contributed to the enamel defects. In this study, we crossed Fam20C(fl/fl) mice with keratin 14-Cre (K14-Cre) transgenic mice to specifically inactivate Fam20C in the epithelial cells, including the dental epithelial cells that are responsible for forming tooth enamel. X-ray, backscattered scanning electron microscopic, and histological analyses showed that the K14-Cre;Fam20C(fl/fl) mice had severe enamel and ameloblast defects, while their dentin and alveolar bone were not significantly affected. Accordingly, serum biochemistry of the K14-Cre;Fam20C(fl/fl) mice showed normal phosphate and FGF23 levels in the circulation. Analysis of these data indicates that, while FAM20C is a molecule essential to amelogenesis, its inactivation in the dental epithelium does not significantly affect dentinogenesis. Hypophosphatemia makes no significant contribution to the enamel defects in the mice with the ubiquitous deletion of Fam20C.

  15. Autosomal dominant inheritance of Weaver syndrome.

    OpenAIRE

    Fryer, A; Smith, C; Rosenbloom, L; Cole, T

    1997-01-01

    Most report of Weaver syndrome have been sporadic cases and the genetic basis of the syndrome is uncertain. This report of an affected father and daughter provides evidence for autosomal dominant inheritance.

  16. State Government Revenue Recovery from the Great Recession

    OpenAIRE

    James Alm; David L. Sjoquist

    2014-01-01

    The "Great Recession" lasted from December 2007 to June 2009, and it wreaked havoc on the revenues of state (and local) governments. While the U.S. economy has improved since the end of the Great Recession, state government revenues have in most cases still not completely recovered. We use various indicators to measure how different states have -- or have not -- recovered in the aftermath of the Great Recession, and we also attempt to explain why these different patterns of recovery have emer...

  17. Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy

    Science.gov (United States)

    Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.

    2016-01-01

    Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753

  18. Development of Web-Based RECESS Model for Estimating Baseflow Using SWAT

    Directory of Open Access Journals (Sweden)

    Gwanjae Lee

    2014-04-01

    Full Text Available Groundwater has received increasing attention as an important strategic water resource for adaptation to climate change. In this regard, the separation of baseflow from streamflow and the analysis of recession curves make a significant contribution to integrated river basin management. The United States Geological Survey (USGS RECESS model adopting the master-recession curve (MRC method can enhance the accuracy with which baseflow may be separated from streamflow, compared to other baseflow-separation schemes that are more limited in their ability to reflect various watershed/aquifer characteristics. The RECESS model has been widely used for the analysis of hydrographs, but the applications using RECESS were only available through Microsoft-Disk Operating System (MS-DOS. Thus, this study aims to develop a web-based RECESS model for easy separation of baseflow from streamflow, with easy applications for ungauged regions. RECESS on the web derived the alpha factor, which is a baseflow recession constant in the Soil Water Assessment Tool (SWAT, and this variable was provided to SWAT as the input. The results showed that the alpha factor estimated from the web-based RECESS model improved the predictions of streamflow and recession. Furthermore, these findings showed that the baseflow characteristics of the ungauged watersheds were influenced by the land use and slope angle of watersheds, as well as by precipitation and streamflow.

  19. Economic recession and suicidal behaviour: Possible mechanisms and ameliorating factors.

    Science.gov (United States)

    Haw, Camilla; Hawton, Keith; Gunnell, David; Platt, Stephen

    2015-02-01

    A growing body of research evidence from countries around the world indicates that economic recession is associated with increases in suicide, particularly in males of working age. To explore contributory and ameliorating factors associated with economic recession and suicide and thereby stimulate further research in this area and encourage policy makers to consider how best to reduce the impact of recession on mental health and suicidal behaviour. We conducted a selective review of the worldwide literature focusing on possible risk factors, mechanisms and preventative strategies for suicidal behaviour linked to economic recession. A model of how recession might affect suicide rates is presented. A major and often prolonged effect of recession is on unemployment and job insecurity. Other important effects include those exerted by financial loss, bankruptcy and home repossession. It is proposed these factors may lead directly or indirectly to mental health problems such as depression, anxiety and binge drinking and then to suicidal behaviour. Countries with active labour market programmes and sustained welfare spending during recessions have less marked increases in suicide rates than those that cut spending on welfare and job-search initiatives for the unemployed. Other measures likely to help include targeted interventions for unemployed people, membership of social organisations and responsible media reporting. Good primary care and mental health services are needed to cope with increased demand in times of economic recession but some governments have in fact reduced healthcare spending as an austerity measure. The research evidence linking recession, unemployment and suicide is substantial, but the evidence for the other mechanisms we have investigated is much more tentative. We describe the limitations of the existing body of research as well as make suggestions for future research into the effects of economic recession on suicidal behaviour. © The Author

  20. The Great Recession and America’s Geography of Unemployment

    Science.gov (United States)

    Thiede, Brian C.; Monnat, Shannon M.

    2017-01-01

    Background The Great Recession of 2007–2009 was the most severe and lengthy economic crisis in the U.S. since the Great Depression. The impacts on the population were multi-dimensional, but operated largely through local labor markets. Objective To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. Methods We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. Results The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. Conclusions The local consequences of macroeconomic trends are associated with county population characteristics, as well as the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state inequality between local labor market conditions. Contribution To present new estimates of the recession’s impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately large recession

  1. Effects of combined gate and ohmic recess on GaN HEMTs

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2016-09-01

    Full Text Available AlGaN/GaN, because of their superior material properties, are most suitable semiconductor material for High Electron Mobility Transistors (HEMTs. In this work we investigated the hidden physics behind these materials and studied the effect of recess technology in AlGaN/GaN HEMTs. The device under investigation is simulated for different recess depth using Silvaco-Atlas TCAD. Recess technology improves the performance of AlGaN/GaN HEMTs. We considered three kinds of recess technology gate, ohmic and combination of gate and ohmic. Gate recess improves transconductance gm but it reduces the drain current Id of the device under investigation. Ohmic recess improves the transconductance gm but it introduces leakage current Ig in the device. In order to use AlGaN/GaN for high voltage operation, both the transconductance and the drain current should be reasonably high which is obtained by combining both gate and ohmic recess technologies. A good balance in transconductance and drain current is achieved by combining both gate and ohmic recess technologies without any leakage current.

  2. Allele frequency distribution for 21 autosomal STR loci in Bhutan.

    Science.gov (United States)

    Kraaijenbrink, Thirsa; van Driem, George L; Tshering of Gaselô, Karma; de Knijff, Peter

    2007-07-20

    We studied the allele frequency distribution of 21 autosomal STR loci contained in the AmpFlSTR Identifiler (Applied Biosystems), the Powerplex 16 (Promega) and the FFFL (Promega) multiplex PCR kits among 936 individuals from the Royal Kingdom of Bhutan. As such these are the first published autosomal DNA results from this country.

  3. Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta.

    Science.gov (United States)

    Santos, Maria C L G; Hart, P Suzanne; Ramaswami, Mukundhan; Kanno, Cláudia M; Hart, Thomas C; Line, Sergio R P

    2007-01-31

    Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

  4. POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kitano

    Full Text Available A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants were successfully identified in 15 probands (2.5% among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants

  5. The Role of Credit in Predicting US Recessions

    DEFF Research Database (Denmark)

    Pönkä, Harri

    are useful predictors of US recessions over and above the control variables both in and out of sample. Especially the excess bond premium, capturing the cyclical changes in the relationship between default risk and credit spreads, is found to be a powerful predictor. Overall, models that combine credit......We study the role of credit in forecasting US recession periods with probit models. We employ both classical recession predictors and common factors based on a large panel of financial and macroeconomic variables as control variables. Our findings suggest that a number of credit variables...

  6. Genetics Home Reference: hypohidrotic ectodermal dysplasia

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... EDARADD gene. EDAR mutations can have an autosomal dominant or autosomal recessive pattern of inheritance, and EDARADD ...

  7. Genetics Home Reference: autosomal dominant hypocalcemia

    Science.gov (United States)

    ... individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include ... sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V. There are two ...

  8. The Recession Squeezes Training.

    Science.gov (United States)

    Geber, Beverly

    1991-01-01

    Recession is having an impact on training departments. Besides a slowdown, it provides managers with a chance to reevaluate programs to ensure they are attuned to the specific goals of the company. (JOW)

  9. Health Impacts of the Great Recession: A Critical Review.

    Science.gov (United States)

    Margerison-Zilko, Claire; Goldman-Mellor, Sidra; Falconi, April; Downing, Janelle

    2016-03-01

    The severity, sudden onset, and multipronged nature of the Great Recession (2007-2009) provided a unique opportunity to examine the health impacts of macroeconomic downturn. We comprehensively review empirical literature examining the relationship between the Recession and mental and physical health outcomes in developed nations. Overall, studies reported detrimental impacts of the Recession on health, particularly mental health. Macro- and individual-level employment- and housing-related sequelae of the Recession were associated with declining fertility and self-rated health, and increasing morbidity, psychological distress, and suicide, although traffic fatalities and population-level alcohol consumption declined. Health impacts were stronger among men and racial/ethnic minorities. Importantly, strong social safety nets in some European countries appear to have buffered those populations from negative health effects. This literature, however, still faces multiple methodological challenges, and more time may be needed to observe the Recession's full health impact. We conclude with suggestions for future work in this field.

  10. A case of peeling skin syndrome

    OpenAIRE

    Anil K Singhal; Devendra K Yadav; Bajrang Soni; Savita Arya

    2017-01-01

    Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparin...

  11. Child Poverty and the Great Recession in the United States

    OpenAIRE

    Marianne Bitler; Hilary Hoynes; Elira Kuka

    2014-01-01

    In the midst of the Great Recession, median real household income fell from $61,597 in 2007 to $57,025 in 2010 and $51,007 in 2012. Given that the effects of the Great Recession on unemployment were greater for less skilled workers the authors expect the effects of the Great Recession on household incomes to be larger in relative terms for individuals in the lower end of the income distribution. To explore this issue, in this paper, they comprehensively examine the effects of the Great Recess...

  12. Aeroacoustical Study of the Tgv Pantograph Recess

    Science.gov (United States)

    NOGER, C.; PATRAT, J. C.; PEUBE, J.; PEUBE, J. L.

    2000-03-01

    The general focus of this aerodynamic noise research, induced by turbulent incompressible flow, is to improve our knowledge of acoustic production mechanisms in the TGV pantograph recess in order to be able to reduce the radiated noise. This work is performed under contract with SNCF as a part of the German-French Cooperation DEUFRAKO K2, and is supported by French Ministries for Transport and Research. Previous studies on TGV noise source locations (DEUFRAKO K) have identified the pantograph recess as one of the important aerodynamic noise sources, for speeds higher than 300 km/h, due to flow separation. The pantograph recess is a very complex rectangular cavity, located both on the power car and the first coach roofs of the TGV, and has not been studied before due to the complex shapes. Its aeroacoustic features are investigated experimentally in a low-subsonic wind tunnel, on a realistic 1/7th scale mock-up both with and without pantographs. Flow velocities, estimated with hot-wire anemometry, and parietal visualizations show the flow to reattach on the recess bottom wall and to separate again at the downstream face. Wall pressure fluctuations and “acoustic” measurements using 14 and 12 in microphones respectively are also measured to qualify the flow: no aerodynamic or acoustic oscillations are observed. The study indicates that the pantograph recess has a different behaviour compared to the usual cavity grazing flows.

  13. Sequence analysis of tyrosinase gene in ocular and oculocutaneous albinism patients: introducing three novel mutations.

    Science.gov (United States)

    Khordadpoor-Deilamani, Faravareh; Akbari, Mohammad Taghi; Karimipoor, Morteza; Javadi, Gholamreza

    2015-01-01

    Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented eyes (in patients with ocular albinism) or hair, skin, and eyes (in individuals with oculocutaneous albinism). It is associated with decreased visual acuity, nystagmus, strabismus, and photophobia. The tyrosinase gene is known to be involved in both oculocutaneous albinism and autosomal recessive ocular albinism. In this study, we aimed to screen the mutations in the TYR gene in the nonsyndromic OCA and autosomal recessive ocular albinism patients from Iran. The tyrosinase gene was examined in 23 unrelated patients with autosomal recessive ocular albinism or nonsyndromic OCA using DNA sequencing and bioinformatics analysis. TYR gene mutations were identified in 14 (app. 60%) albinism patients. We found 10 mutations, 3 of which were novel. No mutation was found in our ocular albinism patients, but one of them was heterozygous for the p.R402Q polymorphism.

  14. Non-Overweight and Overweight Children's Physical Activity during School Recess

    Science.gov (United States)

    Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer L.

    2014-01-01

    Objective: Little research has investigated children's physical activity levels during school recess and the contribution of recess to school day physical activity levels by weight status. The aims of this study were to examine non-overweight and overweight children's physical activity levels during school recess, and examine the contribution of…

  15. Systematic review of recess interventions to increase physical activity.

    Science.gov (United States)

    Ickes, Melinda J; Erwin, Heather; Beighle, Aaron

    2013-08-01

    With the rapid increase in obesity rates among youth, efforts to increase physical activity (PA) have become a priority. School-based strategies for PA promotion must be cost-effective, unobtrusive, and linked to improved academic performance. Efforts to maximize recess PA are advocated because of both health and academic benefits. The purpose of this manuscript was to review recess interventions aimed to improve PA among youth, and make recommendations to develop related best practices. An extensive literature search was conducted to include all primary research articles evaluating any recess intervention with PA as an outcome. The included 13 interventions represented both settings within the U.S and internationally, among preschools and elementary/primary schools. A variety of strategies were used within the design and implementation of each of the interventions including: added equipment/materials, markings, zones, teacher involvement, active video games, activity of the week, and activity cards. Of the included studies, 95% demonstrated positive outcomes as a result of the recess intervention. A number of simple, low-cost strategies can be implemented to maximize the amount of recess time students are allotted. Long-term follow-up studies are warranted for each of the recess strategies identified to be effective.

  16. The differences in physical activity levels in preschool children during free play recess and structured play recess

    Directory of Open Access Journals (Sweden)

    Megan L. Frank

    2018-04-01

    Full Text Available Background/Objective: Physical activity (PA is important in reducing childhood obesity, yet a majority of children are not meeting PA guidelines. Schools have been identified as a place to promote childhood PA. The purpose of this study was to determine the best type of physically active recess period to increase preschool-aged children's PA. Methods: PA was measured via accelerometers in preschool-aged children (n = 29 during three, 30-min recess conditions (control; structured play; free play on separate school days. Tertile splits were performed based on PA during the free play condition and children were divided into three groups: highly, moderately and least active. Results: For the aggregated sample, children were more (p ≤ 0.001 active during the free play (1282 ± 662 counts. min−1 and structured play (1416 ± 448 counts. min−1 recess versus the control condition (570 ± 460 counts. min−1 and activity was not different between the free play and structured conditions. However, children who were the most active during free play (1970 ± 647 counts·min−1 decreased (p ≤ 0.05 activity during structured play (1462 ± 535 counts·min−1, whereas children who were moderately active (1031 ± 112 counts·min−1 or the least (530 ± 239 counts·min−1 active during free play increased activity during structured play (1383 ± 345 counts·min−1 moderately active, 1313 ± 413 counts·min−1 least active. Conclusion: Providing a physically-active recess period will contribute to preschool-aged children meeting the recommended PA guidelines; however, different children may respond in a different way based upon the structure of the recess period.

  17. The Effect of Recessions on Firms’ Boundaries

    DEFF Research Database (Denmark)

    Knudsen, Eirik Sjåholm; Foss, Kirsten

    2014-01-01

    The economic theory of the firm offers conflicting predictions of how the two major effects of recessions, changes in demand and access to credit, affect firm boundaries. Using data on Norwegian firms in the recent recession, we find support for both increased and reduced vertical integration...... explanation for the conflicting theoretical predictions regarding vertical integration in response to demand and credit shocks....

  18. Haemochromatosis gene frequency in a control and diabetic Irish population.

    LENUS (Irish Health Repository)

    Kirk, L

    2009-03-01

    Hereditary haemochromatosis is inherited in an autosomal recessive manner. Two major mutations have been identified and the condition is emerging as one of the most common recessive mutations among subjects of Northern European descendants.

  19. Academic Performance and the Great Recession

    OpenAIRE

    Adamopoulou, Effrosyni; Tanzi, Giulia M.

    2014-01-01

    In this paper we study how the Great Recession affected university students in terms of performance, with a special focus on the dropout probability. To do so, we use individual-level data on a representative sample of university students in Italy in 2007 and 2011. We measure the severity of the recession in terms of increases in adult and youth unemployment rate and we exploit geographical variation to achieve identification. On the one hand, an increase in adult male unemployment rate deter...

  20. Recession-An issue for organizations

    Directory of Open Access Journals (Sweden)

    Daniel GEORGESCU

    2009-12-01

    Full Text Available The reality in all organization is that the directors and board are in the position of highest influence and their primary responsibility is leadership. As such, considering the consequences of a recession such as we currently face is not the time for directors to abdicate their responsibilities – it is time for governance leadership. The directors and the board must think and respond strategically. The article shows a matrix for positioning the general manager in recession that is similarly with BCG matrix and in the final a table with a set of essential questions for helping the board in new strategies building.

  1. Recent declines in cancer incidence: related to the Great Recession?

    Science.gov (United States)

    Gomez, Scarlett Lin; Canchola, Alison J; Nelson, David O; Keegan, Theresa H M; Clarke, Christina A; Cheng, Iona; Shariff-Marco, Salma; DeRouen, Mindy; Catalano, Ralph; Satariano, William A; Davidson-Allen, Kathleen; Glaser, Sally L

    2017-02-01

    In recent years, cancer case counts in the U.S. underwent a large, rapid decline-an unexpected change given population growth for older persons at highest cancer risk. As these declines coincided with the Great Recession, we examined whether they were related to economic conditions. Using California Cancer Registry data from California's 30 most populous counties, we analyzed trends in cancer incidence during pre-recession (1996-2007) and recession/recovery (2008-2012) periods for all cancers combined and the ten most common sites. We evaluated the recession's association with rates using a multifactorial index that measured recession impact, and modeled associations between case counts and county-level unemployment rates using Poisson regression. Yearly cancer incidence rate declines were greater during the recession/recovery (3.3% among males, 1.4% among females) than before (0.7 and 0.5%, respectively), particularly for prostate, lung, and colorectal cancers. Lower case counts, especially for prostate and liver cancer among males and breast cancer, melanoma, and ovarian cancer among females, were associated with higher unemployment rates, irrespective of time period, but independent of secular effects. The associations for melanoma translated up to a 3.6% decrease in cases with each 1% increase in unemployment. Incidence declines were not greater in counties with higher recession impact index. Although recent declines in incidence of certain cancers are not differentially impacted by economic conditions related to the Great Recession relative to pre-recession conditions, the large recent absolute declines in the case counts of some cancer may be attributable to the large declines in unemployment in the recessionary period. This may occur through decreased engagement in preventive health behaviors, particularly for clinically less urgent cancers. Continued monitoring of trends is important to detect any rises in incidence rates as deferred diagnoses come to

  2. Results after gastrocnemius recession in 73 patients.

    Science.gov (United States)

    Molund, Marius; Paulsrud, Øyvind; Ellingsen Husebye, Elisabeth; Nilsen, Fredrik; Hvaal, Kjetil

    2014-12-01

    Very few studies describe the clinical results and complications following the surgical procedure of gastrocnemius recession. To survey the patient reported outcomes in patients operated with gastrocnemius recession as single procedure for various foot conditions. 93 patients operated with gastrocnemius recession as single procedure between 2006 and 2011 were detected in the database. 73 patients responded to the invitation for study participation. Questionnaires containing patient reported satisfaction, complications, plantar flexion power and visual analog pain score were used for evaluation of the postoperative result. 45/73 (62%) patients reported a good or excellent result. 8/73 (11%) patients reported a significant postoperative complication. 16/73 (22%) patients noted reduced or severely reduced plantar flexion power after surgery. VAS pain score significantly decreased from 7.0 before surgery to 1.8 (p=0.015) after surgery for patients with plantar fasciitis (n=18) and from 5.6 to 2.3 (p<0.01) for patients with metatarsalgia (n=28). Patients treated with gastrocnemius recession for plantar fasciitis demonstrated good clinical results. The complication rate was higher than reported by others. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  3. Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    Full Text Available To explore gene therapy strategies for amelogenesis imperfecta (AI, a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5 vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including "pK7" and/or "RGD" motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3 fiber "knob" domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both α(vβ3/α(vβ5 integrins and heparan sulfate proteoglycans (HSPGs highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI.

  4. Genetics Home Reference: Aarskog-Scott syndrome

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Evidence suggests that Aarskog-Scott syndrome is inherited in an autosomal dominant or autosomal recessive pattern in some families, although ...

  5. Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

    KAUST Repository

    Alsemari, Abdulaziz

    2017-11-14

    Most mitochondrial and cytoplasmic aminoacyl-tRNA synthetases (aaRSs) are encoded by nuclear genes. Syndromic disorders resulting from mutation of aaRSs genes display significant phenotypic heterogeneity. We expand aaRSs-related phenotypes through characterization of the clinical and molecular basis of a novel autosomal-recessive syndrome manifesting severe mental retardation, ataxia, speech impairment, epilepsy, short stature, microcephaly, hypogonadism, and growth hormone deficiency.A G>A variant in exon 29 of VARS2 (c.3650G>A) (NM_006295) was identified in the index case. This homozygous variant was confirmed by Sanger sequencing and segregated with disease in the family studied. The c.3650G>A change results in alteration of arginine to histidine at residue 1217 (R1217H) of the mature protein and is predicted to be pathogenic.These findings contribute to a growing list of aaRSs disorders, broadens the spectrum of phenotypes attributable to VARS2 mutations, and provides new insight into genotype-phenotype correlations among the mitochondrial synthetase genes.

  6. Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

    KAUST Repository

    Alsemari, Abdulaziz; Al-Younes, Banan; Goljan, Ewa; Jaroudi, Dyala; BinHumaid, Faisal; Meyer, Brian F.; Arold, Stefan T.; Monies, Dorota

    2017-01-01

    Most mitochondrial and cytoplasmic aminoacyl-tRNA synthetases (aaRSs) are encoded by nuclear genes. Syndromic disorders resulting from mutation of aaRSs genes display significant phenotypic heterogeneity. We expand aaRSs-related phenotypes through characterization of the clinical and molecular basis of a novel autosomal-recessive syndrome manifesting severe mental retardation, ataxia, speech impairment, epilepsy, short stature, microcephaly, hypogonadism, and growth hormone deficiency.A G>A variant in exon 29 of VARS2 (c.3650G>A) (NM_006295) was identified in the index case. This homozygous variant was confirmed by Sanger sequencing and segregated with disease in the family studied. The c.3650G>A change results in alteration of arginine to histidine at residue 1217 (R1217H) of the mature protein and is predicted to be pathogenic.These findings contribute to a growing list of aaRSs disorders, broadens the spectrum of phenotypes attributable to VARS2 mutations, and provides new insight into genotype-phenotype correlations among the mitochondrial synthetase genes.

  7. Purification, crystallization and preliminary crystallographic analysis of the CBS pair of the human metal transporter CNNM4

    International Nuclear Information System (INIS)

    Gómez García, Inmaculada; Oyenarte, Iker; Martínez-Cruz, Luis Alfonso

    2011-01-01

    This work describes the purification and preliminary crystallographic analysis of the CBS-pair regulatory domain of the human ancient domain protein 4 (ACDP4), also known as CNNM4. This work describes the purification and preliminary crystallographic analysis of the CBS-pair regulatory domain of the human ancient domain protein 4 (ACDP4), also known as CNNM4. ACDP proteins represent the least-studied members of the eight different types of magnesium transporters that have been identified in mammals to date. In humans the ACDP family includes four members: CNNM1–4. CNNM1 acts as a cytosolic copper chaperone and has been associated with urofacial syndrome, whereas CNNM2 and CNNM4 have been identified as magnesium transporters. Interestingly, mutations in the CNNM4 gene have clinical consequences that are limited to retinal function and biomineralization and are considered to be the cause of Jalili syndrome, which consists of autosomal recessive cone-rod dystrophy and amelogenesis imperfecta. The truncated protein was overexpressed, purified and crystallized in the orthorhombic space group C222. The crystals diffracted X-rays to 3.6 Å resolution using synchrotron radiation. Matthews volume calculations suggested the presence of two molecules in the asymmetric unit, which were likely to correspond to a CBS module of the CBS pair of CNNM4

  8. A etiologia multifatorial da recessão periodontal The etiologic factors of periodontal recession

    Directory of Open Access Journals (Sweden)

    Karen Ferreira Gazel Yared

    2006-12-01

    Full Text Available A literatura apresenta vários fatores relacionados na etiologia da recessão periodontal, além do processo inflamatório induzido pelo biofilme bacteriano, os quais incluem fatores externos e anatômicos locais. Por meio deste estudo, revistou-se a literatura sobre tais fatores, cujo conhecimento é de grande importância para o ortodontista, contribuindo durante o diagnóstico, planejamento e tratamento ortodôntico propriamente dito.The literature shows that besides dental plaque, some external and anatomic local factors are still related to gingival recession etiology. This study reviewed the literature about those factors, which knownledge is of great benefit to the orthodontist, contributing during diagnostic, planning and orthodontic treatment.

  9. A systematic search for linkage with nonsyndromic recessive deafness in two large Middle Eastern inbred kindreds excludes more than 30% of the genome

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, S.; Korostishevsky, M. [Sackler Faculty of Medicine, Ramat-Aviv (Israel); Frydman, M. [Haim Sheba Medical Center, Tel-Hashomer (Israel)] [and others

    1994-09-01

    It has been estimated that as many as 35 loci may individually cause autosomal recessive non-syndromic deafness. The extreme genetic heterogeneity, limited clinical differentiation and phenotypic assortative mating in many western countries make many families unsuitable for genetic linkage studies. Recently the first of those loci was mapped (to 13q) in two consanguineous families from northern Tunisia. We are studying two large highly consanguineous Middle Eastern kindreds (a total of 26 deaf in 98 sampled individuals). Examination in each family showed no evidence of clinical heterogeneity and indicated an uncomplicated profound bilateral sensorineural deafness. We have been able to exclude the 13q locus as the cause of deafness in each kindred and have also excluded such `candidate` loci as regions as those causing Usher`s syndrome type 1 (11q13)(11p), Usher`s syndrome type II (1q32-q41), Waardenburg syndrome type I (2q37), branchio-oto-renal syndrome (8q12-q13), Monge`s deafness (5q31), and Treacher Collins syndrome (5q31.3-q33.3). To date, no lod scores greater than 1 have been obtained in either kindred using 150 RFLT`s, VNTR`s and highly polymorphic microsatellite markers (CA repeats and tetranucleotides). By Morton`s criterion a minimum of 30% of the autosomal genome can be excluded for each kindred separately.

  10. A familial disorder with low bone density and renal phosphate wasting.

    NARCIS (Netherlands)

    Grondel, I.M.; Deure, J. van der; Zanen, A.L.; Dogger, M.; Heuvel, L.P.W.J. van den

    2009-01-01

    Hereditary forms of renal phosphate wasting have been studied thoroughly in the past years. X-linked Hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets (ARHR) are known genetic disorders in which a

  11. Gingival recession is likely associated with tongue piercings.

    Science.gov (United States)

    Reynolds, Mark A

    2012-09-01

    A convenience sample of 60 subjects (27 male; 33 female) with tongue piercings (case group) and 120 subjects (43 male; 77 female) without tongue piercings (control group), ranging in age from 13 to 28 years, were identified from a mix of races living in a geographic area of low socioeconomic status in Brazil. Subjects were recruited from school groups and university centers between January 2008 and March 2009. For each case, 2 controls were selected on a consecutive basis from the same school according to criteria that included age, gender, smoking, and previous orthodontic treatment. Exclusion criteria included individuals with systemic diseases that might compromise the immune system, as well as antibiotics within 3 months or other medications that could affect the gingival tissues. The key study factor was the use or nonuse of tongue piercings (jewelry). The analysis compared periodontal parameters, such as the occurrence, location, and severity of gingival recession, in subjects with and without tongue jewelry. Gingival recession in the anterior lingual mandibular region was assessed as the primary outcome measure. The study sample was divided according to the presence or absence of gingival recession as well as the severity (1-2, 3, and ≥ 4 mm) of gingival recession. The average age of subjects was similar in the case and control groups (18.9 versus 17.7 years, respectively). Fractures of the anterior teeth were present significantly more frequently in cases than controls (26.7% versus 11.7%, respectively; P piercings (OR = 11.0, 95% confidence interval [CI] 5.02-24.09, P <.001). The severity of recession in this region was also significantly higher (calculated using an ordinal scale) in cases than in controls (P < .001). The final multivariate logistic regression model for occurrence of gingival recession included the variables tongue jewelry (yes/no), age, male gender, and the presence of bleeding on probing in the anterior region. Subjects with tongue

  12. Microtensile bond strength to enamel affected by hypoplastic amelogenesis imperfecta.

    Science.gov (United States)

    Yaman, Batu Can; Ozer, Fusun; Cabukusta, Cigdem Sozen; Eren, Meltem M; Koray, Fatma; Blatz, Markus B

    2014-02-01

    This study compared the microtensile bond strengths (μTBS) of two different self-etching (SE) and etchand- rinse (ER) adhesive systems to enamel affected by hypoplastic amelogenesis imperfecta (HPAI) and analyzed the enamel etching patterns created by the two adhesive systems using scanning electron microscopy (SEM). Sixteen extracted HPAI-affected molars were used for the bond strength tests and 2 molars were examined under SEM for etching patterns. The control groups consisted of 12 healthy third molars for μTBS tests and two molars for SEM. Mesial and distal surfaces of the teeth were slightly ground flat. The adhesive systems and composite resin were applied to the flat enamel surfaces according to the manufacturers' instructions. The tooth slabs containing composite resin material on their mesial and distal surfaces were cut in the mesio-distal direction with a slow-speed diamond saw. The slabs were cut again to obtain square, 1-mm-thick sticks. Finally, each stick was divided into halves and placed in the μTBS tester. Bond strength tests were performed at a speed of 0.5 mm/min. Data were analyzed with two-way ANOVA and Tukey's tests. There was no significant difference between the bond strength values of ER and SE adhesives (p > 0.05). However, significant differences were found between HPAI and control groups (p systems provide similar bond strengths to HPAI-affected enamel surfaces.

  13. Gingival recession: prevalence and risk indicators among young greek adults.

    Science.gov (United States)

    Chrysanthakopoulos, Nikolaos A

    2014-07-01

    The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults.

  14. Gingival recession in smokers and non-smokers with minimal periodontal disease.

    Science.gov (United States)

    Müller, Hans-Peter; Stadermann, Sabine; Heinecke, Achim

    2002-02-01

    Smoking is a major risk factor for destructive periodontal disease. There is limited information with regard to effects of smoking in subjects with minimal periodontal destruction. The aim of the present investigation was to assess the development of gingival recession in young adult smokers and non-smokers. 61 systemically healthy young adults, 19 to 30 years of age completed the final examination. 30 volunteers smoked at least 20 cigarettes per day, whereas 31 subjects were non-smokers. Clinical periodontal conditions were assessed 4x within a time period of 6 months. Site-specific analyses considering the correlated structure of data were performed. At the outset, 50% of subjects presented with gingival recession at 1 or more sites. There was no significant difference in the prevalence of gingival recession between non-smokers and smokers. Severe recession in excess of 2 mm affected about 23% non-smokers but only 7% smokers. Some further gingival recession developed during the 6-month observation period. In a multivariate logistic regression analysis, the risk for recession development appeared not to be influenced by smoking status after adjusting for periodontal probing depth, recession at baseline, tooth brushing frequency, gender, jaw, tooth type and site. Present data did not support the hypothesis that smokers are at an increased risk for the development of gingival recession.

  15. Interdisciplinary management for restoration of function and esthetics in a patient with hereditary amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Sushma Dhiman

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a type of the hereditary disorder which is expressed as a group of conditions causing developmental alterations in the structure of enamel. It is associated with a reduction of oral health-related quality-of-life, has an impact on psychological well-being, and leads to various physiological problems. Children or adults with AI express varying degree of malocclusions either in the form of crowding, impacted teeth, spacing, retained teeth, reduced vertical height due to abnormal tooth structure or undue tooth loss. Orthodontic treatment should precede esthetic rehabilitation. Proper diagnosis of the case is quintessential to provide durable functional and esthetic result to these patients, improving the quality of their lives. We present a case of interdisciplinary management for restoring function and esthetics in a patient with hereditary AI of the hypoplastic type accompanied with tooth impaction and some other dental anomalies.

  16. Disease: H01019 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available by mutations in the cardiac ryanodine receptor gene (RYR2) accounting for an autosomal dominant form (CPVT1)... or mutations in the cardiac calsequestrin gene CASQ2 accounting for an autosomal recessive form (CPVT2). It

  17. Pattern of Glacier Recession in Indian Himalaya

    Science.gov (United States)

    Singh, Ajay; Patwardhan, Anand

    All currently available climate models predict a near-surface warming trend under the influence of rising levels of greenhouse gases in the atmosphere. In addition to the direct effects on climate — for example, on the frequency of heat waves — this increase in surface temperatures has important consequences for the cryosphere subsequently hydrological cycle, particularly in regions where water supply is currently dominated by melting snow or ice. The Indian Himalayan region occupies a special place in the mountain ecosystems of the world. These geodynamically young mountains are not only important from the standpoint of climate and as a provider of life, giving water to a large part of the Indian subcontinent, but they also harbor a rich variety of flora, fauna, human communities and cultural diversity. Glaciers in this region are changing in area as well as in volume like those in other parts of the world. Studies have been carried out for recession in some of these glaciers using remote sensing as well as field observation techniques. Spatiotemporal pattern in the recession rate of the studied glaciers has been presented in this paper. Plausible causes for the recession have been also discussed. Finally, future scopes for observation and analysis in glaciers recession have been suggested.

  18. Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Smith, Claire E L; Murillo, Gina; Brookes, Steven J; Poulter, James A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2016-08-15

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI. However, no AMTN mutations have yet been associated with human AI. Using whole exome sequencing, we identified an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues. Exfoliated primary teeth from an affected family member had enamel that was of a lower mineral density compared to control enamel and exhibited structural defects at least some of which appeared to be associated with organic material as evidenced using elemental analysis. This study demonstrates for the first time that AMTN mutations cause non-syndromic human AI and explores the human phenotype, comparing it with that of mice with disrupted Amtn function. © The Author 2016. Published by Oxford University Press.

  19. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Maria Carolina Salomé Marquezin

    2015-01-01

    Full Text Available The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child’s psychosocial development.

  20. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    Science.gov (United States)

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526