Bardet Biedl syndrome is a genetically heterogeneous ciliopathy with fourteen genes currently identified. To date, mutations in BBS7 and TTC8 (BBS8) were reported in 4.2% and 2.8% of BBS families respectively. We sequenced the coding regions of BBS7 and TTC8 in 35 BBS families of diverse ancestral backgrounds. In addition, the role of putative modifier genes on phenotype severity; NXNL1 and MGC1203 c.430C>T, was assessed. Genotype-phenotype correlation was explored in patients with identified mutations. Four novel pathogenic BBS7 changes were identified in 2/35 families (5.7%). In one family with two affected individuals with BBS7 mutations, a more severe phenotype was observed in association with a third mutation in BBS4. The overall retinal phenotype appeared more severe than that seen in patients with BBS1 mutations. This study confirms the small role of BBS7 and TTC8 in the overall mutational load of BBS patients. The variability of the ocular phenotype observed, could not be explained by the putative modifier genes; NXNL1 and MGC1203 c.430C>T.
(c) 2009 Wiley-Liss, Inc.