Details

Autor(en) / Beteiligte

• Karam, Adella
• Delvallée, Clarisse
• Estrada-Cuzcano, Alejandro
• Geoffroy, Véronique
• Lamouche, Jean-Baptiste
• Leuvrey, Anne-Sophie
• Nourisson, Elsa
• Tarabeux, Julien
• Stoetzel, Corinne
• Scheidecker, Sophie
• Porter, Louise Frances
• Génin, Emmanuelle
• Redon, Richard
• Sandron, Florian
• Boland, Anne
• Deleuze, Jean-François
• Le May, Nicolas
• Dollfus, Hélène
• Muller, Jean

Titel

WGS Revealed Novel BBS5 Pathogenic Variants, Missed by WES, Causing Ciliary Structure and Function Defects

Ist Teil von

• International journal of molecular sciences, 2023-05, Vol.24 (10), p.8729

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.