Genotype-Phenotype Correlations in Bardet-Biedl Syndrome

Daniels, Anthony B.; Sandberg, Michael A.; Chen, Jianjun; Weigel-DiFranco, Carol; Hejtmancik, J. Fielding; Berson, Eliot L.

doi:10.1001/archophthalmol.2012.89

Cited by 66 publications

(69 citation statements)

References 29 publications

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“…[8,9] An age-related evolution of the phenotype is well documented in BBS, [1,6] and the younger age distribution of our cohort may have influenced this. Primary enuresis was common into late childhood and adolescence in our cohort, and likely reflects the recognised urinary concentration deficits that occur in BBS.…”

Section: The New Millenniummentioning

confidence: 81%

“…In the remaining 22 families testing negative for this single mutation, 3 coloured patients have subsequently had causative mutations in other BBS genes identified: 1 with compound heterozygosity in BBS 2 and 2 brothers heterozygous for novel BBS 10 mutations predicted to be disease causing. [6] From the limited information available, a number of patients testing negative did not have more than one or two primary diagnostic criteria, suggesting that the diagnosis may be uncertain. Ethnicity was not documented for all patients, but where available, confirmed that all further positive analyses were found in patients of indigenous black SA descent, with white and coloured patients accounting for a significant number of negative analyses.…”

Section: Resultsmentioning

confidence: 99%

“…[5] Additional reports have expanded both the ocular and systemic phenotype. [6][7][8][9] BBS is typically an autosomal recessive disorder. Although oligogenic inheritance is described, it is a highly heterogeneous condition and to date 21 genes (BBS 1-19, NPHP1 and IFT172) that account for more than 80% of affected individuals have been implicated.…”

Section: To Prof Peter Beighton 'Do Genetics and See The World ' …mentioning

confidence: 99%

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Bardet Biedl syndrome in South Africa: A single founder mutation

et al. 2016

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Background. Bardet Biedl syndrome (BBS) is a multisystem disorder characterised by obesity, polydactyly, intellectual disability and loss of vision due to a progressive retinopathy. Although typically a highly heterogeneous autosomal recessive disease, homozygosity for single mutation in BBS 10 has been identified in a significant number of affected individuals tested in South Africa (SA). Objectives. To delineate the ethnic distribution and clinical phenotype in a cohort of SA BBS patients with the K243IfsX15 mutation in BBS 10 and discuss the implications for genetic testing of and counselling for this disorder in SA.Method. This was a descriptive cross-sectional study collating clinical and laboratory data retrospectively in a genetically homogenous subgroup of BBS patients from SA. Results. A total of 76 patients from 74 families were tested. Homozygosity for the K243IfsX15 BBS 10 mutation was found in 50 families (67%) and heterozygosity for the same mutation in an additional two affected individuals. With the exception of one patient of mixed ancestry, all were black South Africans from different language groups. This is in keeping with the observation that BBS is more common in this ethnic group compared with white and coloured patients in SA, first made by Prof. Beighton nearly 3 decades ago. A subset of 15 patients available for detailed phenotyping confirmed consistency with well-described features of the disorder, with some overlap with other ciliopathies. The onset of visual impairment was early in our cohort, before the age of 8 years, cognitive impairment was significant, and renal and cardiac abnormalities were infrequently encountered. Conclusion. The high frequency of homozygosity for a single mutation in an ethnic subset of the SA population is strongly suggestive of a founder effect. This has allowed establishment of a diagnostic test with a high yield in our local population. Better understanding of the phenotype will improve earlier recognition of the disorder to allow for appropriate intervention. Testing can confirm but not negate a clinical diagnosis, and can permit carrier and prenatal testing in informative families.

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Section: The New Millenniummentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: To Prof Peter Beighton 'Do Genetics and See The World ' …mentioning

confidence: 99%

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Bardet Biedl syndrome in South Africa: A single founder mutation

et al. 2016

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“…For instance, a milder phenotype has been associated with the recurrent mutation p.M390R (BBS1) [Hjortshoj et al, 2010]. Further, in a recent study, ocular phenotype evaluation for 37 BBS patients revealed that patients with BBS1 mutations had a milder phenotype than patients with mutations in other BBS genes [Daniels et al, 2012]. Other reports suggested the association between mutations in BBS1 , BBS2 , BBS3 , and BBS4 and specific ocular phenotypes and digital malformations [Heon et al, 2005].…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

Update on the Genetics of Bardet-Biedl Syndrome

2013

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Bardet-Biedl syndrome (BBS) is an autosomal recessive disease characterized by retinal dystrophy, obesity, postaxial polydactyly, learning disabilities, renal involvement, and male hypogenitalism. BBS is genetically heterogeneous, and to date 18 genes (BBS1-18) have been described. Mutations in known BBS genes account for approximately 70-80% of cases, and triallelic inheritance has been suggested in about 5%. Many minor features can be helpful in making the clinical diagnosis. Recently, the use of next-generation sequencing technologies has accelerated the identification of novel genes and causative disease mutations in known genes. This report presents a concise overview of the current knowledge on clinical data in BBS and the progress in molecular genetics research. A future objective will be the development of BBS diagnosis kits in order to offer genetic counseling for families at risk.

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“…These sensational observations were defined as a 'triallelic inheritance' and became a subject of intensive studies [Katsanis et al, 2001]. Some data sets confirm increased coincidence of homozygous and heterozygous BBS gene mutations in BBS patients, while others deny this relationship [Katsanis et al, 2002;Badano et al, 2003a;Beales et al, 2003;Fauser et al, 2003;Mykytyn et al, 2003;Hichri et al, 2005;Laurier et al, 2006;Smaoui et al, 2006;Hjortshøj et al, 2010;Abu-Safieh et al, 2012;Daniels et al, 2012;Redin et al, 2012]. Furthermore, the mechanistic basis for the pathogenic impact of heterozygous mutations remains largely elusive.…”

Section: Mode Of Inheritancementioning

confidence: 99%

Bardet-Biedl Syndrome

Suspitsin

Imyanitov²

2016

Mol Syndromol

111

122

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Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder. It is characterized by heterogeneous clinical manifestations including primary features of the disease (rod-cone dystrophy, polydactyly, obesity, genital abnormalities, renal defects, and learning difficulties) and secondary BBS characteristics (developmental delay, speech deficit, brachydactyly or syndactyly, dental defects, ataxia or poor coordination, olfactory deficit, diabetes mellitus, congenital heart disease, etc.); most of these symptoms may not be present at birth but appear and progressively worsen during the first and second decades of life. At least 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning. Genetic diagnosis of BBS is complicated due to lack of gene-specific disease symptoms; however, it is gradually becoming more accessible with the invention of multigene sequencing technologies. Clinical management of BBS is largely limited to a symptomatic treatment. Mouse experiments demonstrate that the most debilitating complication of BBS, blindness, can be rescued by topical gene therapy. There is a published case report describing the delay of BBS symptoms by nutritional compensation of the disease-related biochemical deficiencies. Progress in DNA testing technologies is likely to rapidly resolve all limitations in BBS diagnosis; however, much slower improvement is expected with regard to BBS treatment.

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Genotype-Phenotype Correlations in Bardet-Biedl Syndrome

Abstract: These phenotypic differences can help guide genetic testing and genetic counseling for patients with this syndrome.

Cited by 66 publications

References 29 publications

Bardet Biedl syndrome in South Africa: A single founder mutation

Bardet Biedl syndrome in South Africa: A single founder mutation

Update on the Genetics of Bardet-Biedl Syndrome

Bardet-Biedl Syndrome

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