Low prevalence of MYOC mutations in UK primary open-angle glaucoma patients limits the utility of genetic testing
Low prevalence of MYOC mutations in UK primary open-angle glaucoma patients limits the utility of genetic testing
复制标题
DOI：
10.1007/s00439-004-1171-1
复制
发表时间：
2004-10-01
期刊：
影响因子：
5.3
通讯作者：
Trembath, RC
中科院分区：
文献类型：
--
作者：
Aldred, MA;Baumber, L;Trembath, RC
原发性开角型青光眼（POAG）影响了1%的40岁以上人群。早期发现和治疗可以预防失明，但这种疾病通常是无症状的，直到晚期。阳性家族史是一个重要的危险因素，先前的研究表明，大约5%的POAG是由心肌蛋白（MYOC）基因突变引起的，这增加了识别遗传易感性青光眼个体的可能性。我们收集了426名未选择的英国POAG患者的DNA样本，并分析了他们的MYOC突变。6例患者（1.4%）发现Q368X突变。未发现其他突变，这表明在未选择家族史的患者中，英国MYOC突变的患病率低于其他人群。对这6名先证者的一级亲属（第一组）和年龄/性别匹配的突变阴性对照（第二组）进行遗传和青光眼筛查。在11名1组亲属中，有3人携带Q368X基因，其中一人已经患有青光眼。值得注意的是，在两组突变阴性的13名亲属中，有一人已经在接受高眼压治疗。因此，我们警告不要改变这些个体的青光眼监测方案，并建议在确定其他重要的遗传风险因素之前，对POAG患者进行MYOC突变的常规非靶向基因检测价值有限。
Primary open angle glaucoma (POAG) affects 1% of people over age 40. Early detection and treatment can prevent blindness, but the disease is often asymptomatic until a late stage. Positive family history is an important risk factor and previous studies indicate that approximately 5% of POAG results from mutations in the myocilin (MYOC) gene, raising the possibility of identifying individuals genetically predisposed to glaucoma. We collected DNA samples from 426 unselected UK POAG patients and analyzed them for MYOC mutations. The Q368X mutation was found in six patients (1.4%). No other mutations were identified, suggesting that amongst patients unselected for family history, the prevalence of MYOC mutations in the UK is lower than in other populations. Genetic and glaucoma screening was offered to first-degree relatives of these six probands (group 1) and of age/sex-matched mutation-negative controls (group 2). Of 11 group-1 relatives, three carried Q368X, one of whom already had glaucoma. Notably, of the 13 relatives in both groups who were mutation negative, one was already being treated for ocular hypertension. We therefore caution against changing glaucoma surveillance regimens in such individuals and suggest that routine untargeted genetic testing for MYOC mutations in patients with POAG would be of limited value until additional significant genetic risk factors are identified.