Fiche publication
Date publication
mai 2023
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LE MAY Nicolas
Tous les auteurs :
Karam A, Delvallée C, Estrada-Cuzcano A, Geoffroy V, Lamouche JB, Leuvrey AS, Nourisson E, Tarabeux J, Stoetzel C, Scheidecker S, Porter LF, Génin E, Redon R, Sandron F, Boland A, Deleuze JF, Le May N, Dollfus H, Muller J
Lien Pubmed
Résumé
Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy that affects multiple organs, leading to retinitis pigmentosa, polydactyly, obesity, renal anomalies, cognitive impairment, and hypogonadism. Until now, biallelic pathogenic variants have been identified in at least 24 genes delineating the genetic heterogeneity of BBS. Among those, is a minor contributor to the mutation load and is one of the eight subunits forming the BBSome, a protein complex implied in protein trafficking within the cilia. This study reports on a European patient with a severe BBS phenotype. Genetic analysis was performed using multiple next-generation sequencing (NGS) tests (targeted exome, TES and whole exome, WES), and biallelic pathogenic variants could only be identified using whole-genome sequencing (WGS), including a previously missed large deletion of the first exons. Despite the absence of family samples, the biallelic status of the variants was confirmed. The BBS5 protein's impact was confirmed on the patient's cells (presence/absence and size of the cilium) and ciliary function (Sonic Hedgehog pathway). This study highlights the importance of WGS and the challenge of reliable structural variant detection in patients' genetic explorations as well as functional tests to assess a variant's pathogenicity.
Mots clés
BBS5 gene, Bardet–Biedl syndrome, primary cilium, structural variation, whole-genome sequencing
Référence
Int J Mol Sci. 2023 05 13;24(10):
