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