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Published on: August 24, 2013
Genetic predictors of cardiovascular morbidity in Bardet-Biedl syndrome
E Forsythe1, K Sparks, B E Hoskins
1Molecular Medicine Unit, UCL Institute of Child Health, University College London, London, UK.
Insights
Bardet-Biedl syndrome (BBS) patients with BBS10 mutations show higher cardiovascular risk markers than those with BBS1 mutations. Missense mutations in BBS1 are associated with lower cardiovascular disease markers, aiding clinical stratification.
Area of Science:
- Genetics
- Cardiology
- Ciliopathies
Background:
- Bardet-Biedl syndrome (BBS) is a rare ciliopathy with diverse clinical manifestations, including significant cardiovascular disease risk.
- Mutations in BBS1 and BBS10 are the most common genetic causes of BBS.
- Understanding genotype-phenotype correlations is crucial for managing cardiovascular risk in BBS patients.
Purpose of the Study:
- To investigate genotype-phenotype correlations concerning cardiovascular risk indicators in BBS patients.
- To compare cardiovascular risk markers between patients with BBS1 mutations and those with BBS10 mutations.
- To analyze the impact of mutation type (missense, truncating) on cardiovascular risk markers.
Main Methods:
- Compared 50 patients with BBS1 mutations to 19 patients with BBS10 mutations.
- Analyzed cardiovascular risk indicators including C-reactive protein, C-peptide, triglycerides, and gamma-glutamyl transferase.
- Stratified analysis based on mutation type (truncating, missense, compound) and zygosity.
Main Results:
- Patients with BBS10 mutations exhibited higher C-reactive protein and C-peptide levels compared to BBS1 patients.
- Homozygous truncating mutations were linked to elevated C-reactive protein and triglycerides.
- Gamma-glutamyl transferase was higher in homozygous truncating and certain heterozygous mutations.
- Missense mutations in BBS1 were associated with lower biochemical cardiovascular disease markers.
Conclusions:
- Genotype, specifically mutations in BBS1 versus BBS10 and mutation type, influences cardiovascular risk markers in Bardet-Biedl syndrome.
- Patients with BBS1 missense mutations may have a comparatively lower cardiovascular disease risk profile.
- These findings can inform the stratification of clinical services and risk management for BBS patients.
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.
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