May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Bardet-Biedl Syndrome: Identification of Two New Genes (Bbs10 and Bbs12) Defines a New Vertebrate Specific Chaperonine-Like Family
Author Affiliations & Notes
  • H. Dollfus
    Laboratoire EA 3941, Faculte de Medecine, Universite Louis Pasteur, Strasbourg, France
  • C. Stoetzel
    Laboratoire EA 3941, Faculte de Medecine, Universite Louis Pasteur, Strasbourg, France
  • J. Muller
    Bioinformatic Department,
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
  • E. Davies
    McKusick-Nathans Institute of Genetic Medicine and Molecular Biology and Genetics,, John Hopkins University, Baltimore, Maryland
  • D. Bonneau
    Service de génétique, CHU Angers, Angers, France
  • A. Mégarbané
    Laboratoire de génétique, Universite Saint Joseph, Beyrouth, Lebanon
  • P. Beales
    Molecular medecine unit, UCL Institute of Child Health, London, United Kingdom
  • O. Poch
    Bioinformatic Department,
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
  • N. Katsanis
    McKusick-Nathans Institute of Genetic Medicine and Molecular Biology and Genetics,, John Hopkins University, Baltimore, Maryland
  • J.-L. Mandel
    Laboratoire de génétique humaine,
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Collège de France, Paris, France
  • Footnotes
    Commercial Relationships H. Dollfus, None; C. Stoetzel, None; J. Muller, None; E. Davies, None; D. Bonneau, None; A. Mégarbané, None; P. Beales, None; O. Poch, None; N. Katsanis, None; J. Mandel, None.
  • Footnotes
    Support PHRc 2002, RETINA France, PNRV INSERM, , NICD,NIDDK, Polycystic kidney foundation,
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 6003. doi:
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      H. Dollfus, C. Stoetzel, J. Muller, E. Davies, D. Bonneau, A. Mégarbané, P. Beales, O. Poch, N. Katsanis, J.-L. Mandel; Bardet-Biedl Syndrome: Identification of Two New Genes (Bbs10 and Bbs12) Defines a New Vertebrate Specific Chaperonine-Like Family. Invest. Ophthalmol. Vis. Sci. 2007;48(13):6003.

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Abstract

Purpose:: The phenotype of Bardet-Biedl syndrome (BBS) is defined by the association of retinitis pigmentosa, obesity, polydactyly, hypogenitalism, renal disease and cognitive impairment. The significant genetic heterogeneity of this condition is supported by the identification, initially by classical linkage analysis and more recently by comparative genomics, of at least a dozen genes implicated in cilia assembly or function. We aimed to identify new genes responsible for BBS.

Methods:: SNP homozygosity mapping was performed on a large cohort of consanguineous BBS families. Bioinformatic analysis was used to select and study candidate genes.

Results:: This approach permitted the identification on chromosome 12 of a major BBS gene: BBS10 by way of the analysis of a large consanguineous Lebanese family. Further analysis of the cohort revealed that this gene is mutated in at least 20 % of families (extracted from the French, US and British BBS cohorts). Bioinformatic studies revealed that BBS10 encodes for a chaperonine-like protein. Using the same SNP homozygosity mapping strategy, by way of the analysis of two gypsy families, we were able to identify the BBS12 gene that accounts for about 5% of the mutational load in BBS.

Conclusions:: Unlike other BBBS genes, BBS10, BBS12 and the previously described BBS6 genes are vertebrate specific and would have been missed by comparative genomics approaches that were successful for other BBS genes. They define a new chaperonine-like family that is important for the pathogenesis of this syndromic form of retinitis pigmentosa.

Keywords: gene mapping • retinal degenerations: hereditary • proteins encoded by disease genes 
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