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J Med Genet 51:132-136 doi:10.1136/jmedgenet-2013-101785
  • New disease loci
  • Short report

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

  1. Hélène Dollfus1,5
  1. 1Laboratoire de Génétique Médicale, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
  2. 2Institut für Toxikologie und Genetik Campus Nord, Karlsruher Institut für Technologie, Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen, Germany
  3. 3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA
  4. 4Plate-forme Bioinformatique de Strasbourg, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch, France
  5. 5Service de Génétique Médicale, Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  6. 6Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  7. 7Integrative Genomics and Bioinformatics Laboratory, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), CNRS UMR7104, INSERM U964, ICube UMR 7357, Université de Strasbourg, Illkirch, France
  8. 8Service de Cytogénétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  1. Correspondence to Professor Helene Dollfus, Faculté de Médecine, Université de Strasbourg, Laboratoire de Génétique Médicale, INSERM 1112, Faculté de Médecine, Bâtiment 3, 11 rue Humann, Strasbourg 67085, France; dollfus{at}unistra.fr
  • Received 26 April 2013
  • Revised 27 July 2013
  • Accepted 16 August 2013
  • Published Online First 11 September 2013

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.