Novel homozygous mutations in the genes ARL6 and BBS10 underlying Bardet–Biedl syndrome

Bardet–Biedl syndrome (BBS) is an autosomal recessive disorder resulting from structural and functional defects in numerous organs. Frequent manifestations reported in the syndrome include obesity, renal dysplasia, cognitive impairment, postaxial polydactyly, pigmentary retinal degeneration and hypogonadism. To date, 17 genes causing BBS have been identified. Two of these BBS1 and BBS10 are the most frequently mutated genes.The present report describes two consanguineous families (A, B) with clinical manifestations of BBS. Linkage in the family A was established to ARL6 on chromosome 3q11.2, while family B showed linkage to BBS10 on chromosome 12q21.2. Sequence analysis revealed a novel homozygous missense mutation (c.281T>C, p.Ile94Thr) in the gene ARL6 in family A and a nonsense mutation (c.1075C>T, p.Gln359*) in the gene BBS10 in family B. Mutations identified in the present study extend the body of evidence implicating the genes ARL6 and BBS10 in causing Bardet–Biedl syndrome.

► Characterization of BBS in two families of Pakistani origin ► Mapping of the families to BBS3 and BBS10 genes ► Novel homozygous mutations in BBS3 and BBS10 genes