High prevalence of Bardet-Biedl syndrome in La Réunion Island is due to a founder variant in ARL6/BBS3.

Clinical genetics 2020 Aug

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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 Réunion 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 Réunion Island. Being the first description of BBS patients from La Réunion Island, we could estimate its prevalence between ~1/45000 and ~ 1/66000 individuals. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

Aurélie Gouronc, Vincent Zilliox, Marie-Line Jacquemont, Françoise Darcel, Anne-Sophie Leuvrey, Elsa Nourisson, Manuela Antin, Jean-Luc Alessandri, Bérénice Doray, Paul Gueguen, Frédérique Payet, Hanitra Randrianaivo, Corinne Stoetzel, Sophie Scheidecker, Hugues Flodrops, Hélène Dollfus, Jean Muller. High prevalence of Bardet-Biedl syndrome in La Réunion Island is due to a founder variant in ARL6/BBS3. Clinical genetics. 2020 Aug;98(2):166-171