Genetic predictors of cardiovascular morbidity in Bardet-Biedl syndrome
Genetic predictors of cardiovascular morbidity in Bardet-Biedl syndrome
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DOI：
10.1111/cge.12373
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发表时间：
2015-04-01
影响因子：
3.5
通讯作者：
Beales, P. L.
中科院分区：
文献类型：
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作者：
Forsythe, E.;Sparks, K.;Beales, P. L.
Bardet-Biedl综合征是一种罕见的睫状体病，以视网膜营养不良、肥胖、智力障碍、多指（趾）畸形、性腺功能减退和肾损害为特征。患者患心血管疾病的风险很高。BBS 1和BBS 10的突变占分子诊断确认的一半以上。为了阐明基因型-表型与心血管风险指标的相关性，将50例BBS 1突变患者与19例携带BBS 10突变的患者进行了比较。所有患者都有截短、错义或复合错义/截短突变。分析了基因型和突变类型的影响。C-反应蛋白在BBS 10突变和纯合截短突变的患者中更高（分别为p=0.013和p=0.002）。BBS 10突变患者的C肽水平高于BBS 1突变患者（p=0.043）。纯合截短突变患者的甘油三酯水平显著升高（p=0.048）。与纯合错义突变患者相比，纯合截短突变患者（p=0.007）和杂合错义和截短突变患者（p=0.002）的γ谷氨酰转移酶更高。将结果与临床心血管危险因素进行比较。与BBS 10和其他BBS 1突变患者相比，BBS 1错义突变患者的生化心血管疾病标志物较低。这可能有助于临床服务的分层。
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.