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. Epub 2013 Sep 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bardet-Biedl Syndrome / genetics*
  • Bardet-Biedl Syndrome / metabolism
  • Base Sequence
  • Carrier Proteins / genetics*
  • Codon, Nonsense*
  • Consanguinity
  • DNA Mutational Analysis
  • Exome*
  • Fibroblasts / metabolism
  • Genetic Association Studies
  • Genetic Linkage
  • HEK293 Cells
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Zebrafish

Substances

  • BBIP1 protein, human
  • Carrier Proteins
  • Codon, Nonsense