High prevalence of Bardet-Biedl syndrome in La Réunion Island is due to a founder variant in ARL6/BBS3
| Autor: | Sophie Scheidecker, Hugues Flodrops, Jean-Luc Alessandri, Corinne Stoetzel, Aurélie Gouronc, Hélène Dollfus, Manuela Antin, Paul Gueguen, Marie-Line Jacquemont, Bérénice Doray, Françoise Darcel, Frédérique Payet, Hanitra Randrianaivo, Vincent Zilliox, Jean Muller, Elsa Nourisson, Anne-Sophie Leuvrey |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities Adolescent Genotype Genetic counseling 030105 genetics & heredity Biology Polymorphism Single Nucleotide 03 medical and health sciences Bardet–Biedl syndrome Genetics medicine Humans Genetic Predisposition to Disease Child Genotyping Bardet-Biedl Syndrome Genetics (clinical) Alleles Polydactyly ADP-Ribosylation Factors Haplotype medicine.disease Founder Effect Pedigree Ciliopathy 030104 developmental biology Haplotypes Child Preschool Mutation Female Founder effect SNP array |
| Zdroj: | Clinical geneticsREFERENCES. 98(2) |
| ISSN: | 1399-0004 |
| Popis: | Bardet-Biedl syndrome (BBS) is a rare ciliopathy with variable retinal dystrophy, polydactyly, renal abnormalities, obesity, cognitive impairment, and hypogonadism. Biallelic pathogenic variants have been identified in 24 genes, leading to BBS in an autosomal recessive inheritance pattern. In this study, we investigated a cohort of 16 families (20 individuals) presenting with typical BBS originating from La Reunion Island using sequencing (Sanger and high-throughput methods) and SNP array. In eight families (12 individuals) we identified the same ARL6/BBS3 variation [c.535G > A, p.(Asp179Asn)]. Bioinformatics and functional analyses revealed an effect of this variant on the splicing of ARL6/BBS3. Owing to the relatively high frequency of this variant, a possible founder effect was suspected. Genotyping of six individuals revealed a common 3.8-Mb haplotype and estimated the most recent common ancestor to about eight generations confirmed by the known genealogy. Knowledge of this founder effect modifies our diagnostic strategy and enables a personalized genetic counseling for patients from La Reunion Island. Being the first description of BBS patients from La Reunion Island, we could estimate its prevalence between ~1/45000 and ~ 1/66000 individuals. |
| Databáze: | OpenAIRE |
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