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Val C Sheffield - One of the best experts on this subject based on the ideXlab platform.
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Inactivation of Bardet-Biedl Syndrome genes causes kidney defects
American journal of physiology. Renal physiology, 2010Co-Authors: Deng-fu Guo, Val C Sheffield, Andreas M. Beyer, Baoli Yang, Darryl Y. Nishimura, Kamal RahmouniAbstract:Bardet-Biedl Syndrome (BBS) is a rare hereditary autosomal recessive disease associated with several features including obesity, hypertension, and renal abnormalities. The underlying mechanisms of ...
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Recurrence risks for Bardet-Biedl Syndrome: Implications of locus heterogeneity
Genetics in Medicine, 2010Co-Authors: Julie C Sapp, Edwin M. Stone, Val C Sheffield, Elise Héon, Darryl Nishimura, Jennifer J Johnston, Leslie G BieseckerAbstract:Purpose: Bardet-Biedl Syndrome is a pleiotropic multiple anomaly Syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl Syndrome. Methods: Mutation data from 187 probands affected with Bardet-Biedl Syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Results: Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Conclusion: Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results.
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Ocular phenotypes of three genetic variants of Bardet-Biedl Syndrome.
American journal of medical genetics. Part A, 2004Co-Authors: Elise Héon, Edwin M. Stone, Carol Westall, Rivka Carmi, Khalil Elbedour, Carole Panton, Leslie Mackeen, Val C SheffieldAbstract:Bardet-Biedl Syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl Syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl Syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond Syndrome.
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Ocular phenotypes of three genetic variants of Bardet–Biedl Syndrome
American Journal of Medical Genetics Part A, 2004Co-Authors: Elise Héon, Edwin M. Stone, Carol Westall, Rivka Carmi, Khalil Elbedour, Carole Panton, Leslie Mackeen, Val C SheffieldAbstract:Bardet-Biedl Syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl Syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl Syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond Syndrome.
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The molecular genetics of Bardet-Biedl Syndrome.
Current opinion in genetics & development, 2001Co-Authors: Val C Sheffield, Darryl Y. Nishimura, Edwin M. StoneAbstract:Bardet–Biedl Syndrome (BBS) has been shown to be a genetically heterogeneous disorder involving genes mapping to at least six known loci. One BBS gene (MKKS) has been identified and the form of the disorder caused by this gene is allelic to McKusick–Kaufman Syndrome. MKKS codes for a putative chaperonin, suggesting that other BBS genes may also code for components of chaperone complexes or be substrates of chaperone function.
Edwin M. Stone - One of the best experts on this subject based on the ideXlab platform.
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Recurrence risks for Bardet-Biedl Syndrome: Implications of locus heterogeneity
Genetics in Medicine, 2010Co-Authors: Julie C Sapp, Edwin M. Stone, Val C Sheffield, Elise Héon, Darryl Nishimura, Jennifer J Johnston, Leslie G BieseckerAbstract:Purpose: Bardet-Biedl Syndrome is a pleiotropic multiple anomaly Syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl Syndrome. Methods: Mutation data from 187 probands affected with Bardet-Biedl Syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Results: Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Conclusion: Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results.
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Ocular phenotypes of three genetic variants of Bardet-Biedl Syndrome.
American journal of medical genetics. Part A, 2004Co-Authors: Elise Héon, Edwin M. Stone, Carol Westall, Rivka Carmi, Khalil Elbedour, Carole Panton, Leslie Mackeen, Val C SheffieldAbstract:Bardet-Biedl Syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl Syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl Syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond Syndrome.
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Ocular phenotypes of three genetic variants of Bardet–Biedl Syndrome
American Journal of Medical Genetics Part A, 2004Co-Authors: Elise Héon, Edwin M. Stone, Carol Westall, Rivka Carmi, Khalil Elbedour, Carole Panton, Leslie Mackeen, Val C SheffieldAbstract:Bardet-Biedl Syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl Syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl Syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond Syndrome.
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The molecular genetics of Bardet-Biedl Syndrome.
Current opinion in genetics & development, 2001Co-Authors: Val C Sheffield, Darryl Y. Nishimura, Edwin M. StoneAbstract:Bardet–Biedl Syndrome (BBS) has been shown to be a genetically heterogeneous disorder involving genes mapping to at least six known loci. One BBS gene (MKKS) has been identified and the form of the disorder caused by this gene is allelic to McKusick–Kaufman Syndrome. MKKS codes for a putative chaperonin, suggesting that other BBS genes may also code for components of chaperone complexes or be substrates of chaperone function.
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Bardet-Biedl Syndrome
Retinal Degenerative Diseases and Experimental Therapy, 1999Co-Authors: Alessandro Iannaccone, Edwin M. Stone, Neena B Haider, Benedetto Falsini, Giuseppe Del Porto, Val C SheffieldAbstract:Herein reported are the systemic and ophthalmologic features of four patients with Bardet-Biedl Syndrome (BBS) from a consanguineous pedigree. Molecular genetic analyses showed linkage with the BBS4 locus (chromosome 15), and excluded linkage to the other known loci on chromosome 3 (BBS3), 11 (BBS1), and 16 (BBS2), respectively. Patients were 15 to 26 years old (M = 3; F = 1) at last examination, and followup was up to 10 years. An array of clinical and functional tests were performed to characterize the ocular phenotype of this pedigree.
Elise Héon - One of the best experts on this subject based on the ideXlab platform.
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Recurrence risks for Bardet-Biedl Syndrome: Implications of locus heterogeneity
Genetics in Medicine, 2010Co-Authors: Julie C Sapp, Edwin M. Stone, Val C Sheffield, Elise Héon, Darryl Nishimura, Jennifer J Johnston, Leslie G BieseckerAbstract:Purpose: Bardet-Biedl Syndrome is a pleiotropic multiple anomaly Syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl Syndrome. Methods: Mutation data from 187 probands affected with Bardet-Biedl Syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Results: Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Conclusion: Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results.
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Ocular phenotypes of three genetic variants of Bardet-Biedl Syndrome.
American journal of medical genetics. Part A, 2004Co-Authors: Elise Héon, Edwin M. Stone, Carol Westall, Rivka Carmi, Khalil Elbedour, Carole Panton, Leslie Mackeen, Val C SheffieldAbstract:Bardet-Biedl Syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl Syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl Syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond Syndrome.
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Ocular phenotypes of three genetic variants of Bardet–Biedl Syndrome
American Journal of Medical Genetics Part A, 2004Co-Authors: Elise Héon, Edwin M. Stone, Carol Westall, Rivka Carmi, Khalil Elbedour, Carole Panton, Leslie Mackeen, Val C SheffieldAbstract:Bardet-Biedl Syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl Syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl Syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond Syndrome.
Nicholas Katsanis - One of the best experts on this subject based on the ideXlab platform.
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eLS - Bardet‐Biedl Syndrome, an Oligogenic Disease
Encyclopedia of Life Sciences, 2007Co-Authors: Yangfan Liu, Norann A. Zaghloul, Nicholas KatsanisAbstract:Bardet-Biedl Syndrome (BBS) is a rare multisystemic disorder characterized by defects in renal function, obesity, mental retardation, retinal degeneration and polydactyly. The disease is transmitted primarily in an autosomal recessive fashion but can also exhibit oligogenic inheritance. Twelve BBS genes have been identified to date. Based on localization and functional studies of their protein products, the underlying cause of the disease phenotype is defects in ciliary function which accounts for the pleiotropic nature of the disease. Though it is still unclear exactly how these genes function in cellular signalling pathways, evidence suggests that they are important in a number of fundamental pathways, including the Wnt signalling pathway. Keywords: Bardet-Biedl Syndrome; cilium; basal body; oligogenic; Wnt
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Dissection of epistasis in oligogenic Bardet–Biedl Syndrome
Nature, 2006Co-Authors: Jose L. Badano, Philip L. Beales, Carmen C Leitch, Stephen J. Ansley, Helen May-simera, Shaneka Lawson, Richard Alan Lewis, Harry C. Dietz, Shannon Fisher, Nicholas KatsanisAbstract:Epistasis, a phenomenon in which one gene influences the expression of a second gene at a different locus, is a major source of genetic variation, but the mechanisms involved have not been analysed in detail. Now Badano et al . have succeeded in demonstrating and closely examining epistasis in Bardet–Biedl Syndrome, an illness often characterized by obesity and learning deficits. The severity of symptoms varies dramatically among patients with this disorder, in line with different combinations of mutations at different genes. A modifier gene called MGC1203 interacts with other genes known to be mutated in Bardet–Biedl Syndrome, leading to a more severe form of the disease. Epistatic interactions have an important role in phenotypic variability, yet the genetic dissection of such phenomena remains challenging^ 1 . Here we report the identification of a novel locus, MGC1203 , that contributes epistatic alleles to Bardet–Biedl Syndrome (BBS), a pleiotropic, oligogenic disorder^ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . MGC1203 encodes a pericentriolar protein that interacts and colocalizes with the BBS proteins. Sequencing of two independent BBS cohorts revealed a significant enrichment of a heterozygous C430T mutation in patients, and a transmission disequilibrium test (TDT) showed strong over-transmission of this variant. Further analyses showed that the 430T allele enhances the use of a cryptic splice acceptor site, causing the introduction of a premature termination codon (PTC) and the reduction of steady-state MGC1203 messenger RNA levels. Finally, recapitulation of the human genotypes in zebrafish shows that modest suppression of mgc1203 exerts an epistatic effect on the developmental phenotype of BBS morphants. Our data demonstrate how the combined use of biochemical, genetic and in vivo tools can facilitate the dissection of epistatic phenomena, and enhance our appreciation of the genetic basis of phenotypic variability.
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The oligogenic properties of Bardet-Biedl Syndrome.
Human molecular genetics, 2004Co-Authors: Nicholas KatsanisAbstract:Bardet-Biedl Syndrome (BBS: OMIM 209900) is a rare developmental disorder that exhibits significant clinical and genetic heterogeneity. Although modeled initially as a purely recessive trait, recent data have unmasked an oligogenic mode of disease transmission, in which mutations at different BBS loci can interact genetically in some families to cause and/or modify the phenotype. Here, I will review and discuss recent advances in elucidating both genetic and cellular aspects of this phenotype and their potential application in understanding the genetic basis of phenotypic variability and oligogenic inheritance.
Habiba Chaabouni-bouhamed - One of the best experts on this subject based on the ideXlab platform.
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Prevalence of Bardet–Biedl Syndrome in Tunisia
Journal of Community Genetics, 2011Co-Authors: Oussama M’hamdi, Ines Ouertani, Faouzi Maazoul, Habiba Chaabouni-bouhamedAbstract:Bardet–Biedl Syndrome (BBS, OMIM 209900) is a ciliopathy causing multivisceral abnormalities. This disease is mainly characterized by obesity, post-axial polydactyly, hypogenitalism, intellectual disabilities, pigmentary retinopathy, and renal deficiency. The prevalence of BBS has been estimated in different populations, ranging from 1 in 160,000 in European populations to 1 in 13,000 in Bedouins from Kuwait. In the present report, we present the first epidemiological study of Bardet–Biedl Syndrome in Tunisia. From 1984 to 2009, 46 Tunisian families, including 67 affected members, were diagnosed as BBS. The patients’ ages ranged between 6 months and 37 years, with median age of 10.4 years. High level of consanguinity was noted in our cohort (93.47%). The overall minimum prevalence in our population was estimated to be approximately 1 in 156,000 individuals. Our study reflects the actual frequency of BBS in North Africa and showed that this disease seems uncommon.
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Prevalence of Bardet-Biedl Syndrome in Tunisia.
Journal of community genetics, 2011Co-Authors: Oussama M’hamdi, Ines Ouertani, Faouzi Maazoul, Habiba Chaabouni-bouhamedAbstract:Bardet–Biedl Syndrome (BBS, OMIM 209900) is a ciliopathy causing multivisceral abnormalities. This disease is mainly characterized by obesity, post-axial polydactyly, hypogenitalism, intellectual disabilities, pigmentary retinopathy, and renal deficiency. The prevalence of BBS has been estimated in different populations, ranging from 1 in 160,000 in European populations to 1 in 13,000 in Bedouins from Kuwait. In the present report, we present the first epidemiological study of Bardet–Biedl Syndrome in Tunisia. From 1984 to 2009, 46 Tunisian families, including 67 affected members, were diagnosed as BBS. The patients’ ages ranged between 6 months and 37 years, with median age of 10.4 years. High level of consanguinity was noted in our cohort (93.47%). The overall minimum prevalence in our population was estimated to be approximately 1 in 156,000 individuals. Our study reflects the actual frequency of BBS in North Africa and showed that this disease seems uncommon.