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

  • J Med Genet. 2014 Feb;51(2):132-6. doi: 10.1136/jmedgenet-2013-101785.
Sophie Scheidecker  1 ,  Christelle Etard ,  Nathan W Pierce ,  Véronique Geoffroy ,  Elise Schaefer ,  Jean Muller ,  Kirsley Chennen ,  Elisabeth Flori ,  Valérie Pelletier ,  Olivier Poch ,  Vincent Marion ,  Corinne Stoetzel ,  Uwe Strähle ,  Maxence V Nachury ,  Hélène Dollfus
Affiliations
  • 1. Laboratoire de Génétique Médicale, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
PMID: 24026985 DOI: 10.1136/jmedgenet-2013-101785
Abstract

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.

Keywords
Clinical Genetics; Diagnostics Tests; Genetic Screening/Counselling; Molecular Genetics; Ophthalmology.