Abstract
Bardet–Biedl syndrome is a rare ciliopathy characterized by retinal dystrophy, obesity, intellectual disability, polydactyly, hypogonadism and renal impairment. Patients are at high risk of cardiovascular disease. Mutations in BBS1 and BBS10 account for more than half of those with molecular confirmation of the diagnosis. To elucidate genotype–phenotype correlations with respect to cardiovascular risk indicators 50 patients with mutations in BBS1 were compared with 19 patients harbouring BBS10 mutations. All patients had truncating, missense or compound missense/truncating mutations. The effect of genotype and mutation type was analysed. C-reactive protein was higher in those with mutations in BBS10 and homozygous truncating mutations (p = 0.013 and p = 0.002, respectively). Patients with mutations in BBS10 had higher levels of C peptide than those with mutations in BBS1 (p = 0.043). Triglyceride levels were significantly elevated in patients with homozygous truncating mutations (p = 0.048). Gamma glutamyl transferase was higher in patients with homozygous truncating mutations (p = 0.007) and heterozygous missense and truncating mutations (p = 0.002) than those with homozygous missense mutations. The results are compared with clinical cardiovascular risk factors. Patients with missense mutations in BBS1 have lower biochemical cardiovascular disease markers compared with patients with BBS10 and other BBS1 mutations. This could contribute to stratification of the clinical service.
Highlights
As C-reactive protein (CRP) is a physiological marker of inflammation and infection, it is notable that there was no statistically significant difference in white cell count or weight between patients with different genes or mutation types. This suggests that patients with missense mutations in BBS1 may be at lower risk of cardiovascular disease than patients with BBS10 or other mutations in BBS1
Our results demonstrate that patients with mutations in BBS10 have significantly higher levels of C-peptide indicating insulin resistance, supporting the suggestion that they are at higher risk of cardiovascular disease than patients with mutations in BBS1
We demonstrated a statistically significant increase in gamma glutamyl transferase (GGT) in patients with homozygous truncating mutations and heterozygous truncating and missense mutations compared with patients with homozygous missense mutations
Summary
Two hundred and thirty nine patients attending the national Bardet-Biedl Syndrome clinics in London and Birmingham were assessed for height, weight, blood pressure, BBS mutation analysis, full blood count, renal function, liver function, inflammatory markers, endocrine and lipid profile. Information on cardiovascular risk factors was collected retrospectively from patient notes. Referrals were made primarily via the British national patient support group and clinical geneticists in the United Kingdom. Sequencing of the four most common mutations: M390R in BBS1, and Y24X and R275X in BBS2 and C91LfsX5 in BBS10. Where only one mutation was found, full sequencing of the relevant gene was performed to identify a second mutation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
