Molecular Characterization of Bardet–Biedl Syndrome in a Native Indian Dogrib Family.

Abstract

Abstract: : Purpose: Bardet–Biedl Syndrome(BBS) is a rare, genetically heterogeneous disease with variable phenotypic characteristics including retinal dystrophy, polydactyly, obesity, hypogonadism, and renal malformation. Eight loci for the disease have been described, and six genes have been characterized. The aim of this study is to determine the molecular characterization of a Native Indian family from the Northwest Territories affected with BBS. Methods: Linkage analysis was performed on a consanguineous Native Indian(Dogrib tribe) family from the Northwest Territories, consisting of 4 individuals affected with BBS and 12 unaffected individuals over two generations. Genotyping was done using polymorphic markers covering the eight BBS candidate loci; BBS1(D11S1238–D11S2371), BBS2(D16S3253–D16S3057), BBS3(D3S2465–D3S3045), BBS4(D15S153–D15S653), BBS5(D2S1353–D2S1391), BBS6(D20S851–D20S604), BBS7(D4S2392–D4S1615), and BBS8(D14S606–D14S617). Results: Affected individuals had a full blown BBS phenotype including impairment of renal function. Based on autosomal recessive inheritance, haplotype analysis provided exclusion of linkage to all BBS loci except for BBS2 (OMIM 606151). Mutational characterization is currently underway. Conclusions:This provides the first documentation of molecular characterization of BBS in a Native Indian family. Genotype/phenotype correlations will be examined further when mutational analysis is complete.

Keywords: genetics • linkage analysis • candidate gene analysis