Mutationsanalysen in BBS1 bei Patienten mit Bardet-Biedl-Syndrom

Bardet-Biedl syndrome (BBS; OMIM 209900) is a genetically heterogeneous autosomal recessive disorder characterised by multiple features such as polydactyly, retinal degeneration, obesity, cognitive impairment, hypogenitalism and renal anomalies. BBS appears to be caused by ciliary dysfunction. Of the known 12 BBS genes, BBS1 is one of the most commonly mutated, and a single missense mutation (p.M390R) accounts for 18-32 % of BBS in Caucasian population. Fifty-one patients with BBS (39 German, 10 Turkish and 2 of other origin) were screened for mutations in BBS1 using the method of single strand conformational analysis (SSCA). Furthermore a questionnaire about the clinical symptoms of BBS was sent to all participating families. Thirty questionnaires were received and analysed. In comparison to the literature the primary symptoms polydactyly, retinal degeneration, obesity and cognitive impairment were the most frequently described features in BBS patients of this cohort. The mutation screening in BBS1 showed eight different sequence variations in 10 patients with BBS (2 polymorphisms and 6 mutations with propable pathogenic relevance). Four of the eight sequence variations are newly described in this work. The missense mutation (p.M390R) was found in 6 of the 51 BBS patients (2 heterogeneous and 4 homogeneous).The allele frequency of 10 % is consistent with the international data (14 %). The results of mutation screening in families of the analysed cohort showed that BBS is not only inherited in an autosomal recessive manner but in some cases a more complex fashion of inheritance like the oligogenic trait must be assumed.