Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18)

Sophie Scheidecker (1) , Christelle Etard , Nathan W. Pierce , Véronique Geoffroy (1) , Elise Schaefer (1) , Jean Muller (2, 1) , Kirsley Chennen , Elisabeth Flori (1) , Valérie Pelletier , Olivier Poch (2) , Vincent Marion (1) , Corinne Stoetzel (1) , Uwe Strahle , Maxence V. Nachury , Helene Dollfus (1)

1 LGM - Laboratoire de Génétique Médicale
2 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie

BACKGROUND: Bardet-Biedl syndrome (BBS) is a recessive and genetically heterogeneous ciliopathy characterised by retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioural dysfunction and hypogonadism. 7 of the 17 BBS gene products identified to date assemble together with the protein BBIP1/BBIP10 into the BBSome, a protein complex that ferries signalling receptors to and from cilia. METHODS AND RESULTS: Exome sequencing performed on a sporadic BBS case revealed for the first time a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. This mutation is pathogenic since no BBIP1 protein could be detected in fibroblasts from the patient, and BBIP1[Leu58*] is unable to associate with the BBSome subunit BBS4. CONCLUSIONS: These findings identify BBIP1 as the 18th BBS gene (BBS18) and suggest that BBSome assembly may represent a unifying pathomechanism for BBS.

Domaines: Génétique

Sophie Scheidecker, Christelle Etard, Nathan W. Pierce, Véronique Geoffroy, Elise Schaefer, et al.. Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). Journal of Medical Genetics, 2014, 51 (2), pp.132-136. ⟨10.1136/jmedgenet-2013-101785⟩. ⟨hal-04255333⟩