A prevalent and three novel mutations in CYP11B1 gene identified in Chinese patients with 11-beta hydroxylase deficiency
A prevalent and three novel mutations in CYP11B1 gene identified in Chinese patients with 11-beta hydroxylase deficiency
复制标题
在中国 11-β 羟化酶缺乏症患者中发现了 CYP11B1 基因的一个常见突变和三个新突变
DOI：
10.1016/j.jsbmb.2012.08.011
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发表时间：
2013-01-01
影响因子：
4.1
通讯作者：
Li, Xiaoying
中科院分区：
文献类型：
--
作者：
Zhang, Manna;Liu, Yanling;Li, Xiaoying
11 β -羟化酶缺乏症（11 β - ohd）是由CYP11B1突变引起的，以低肾上腺素血症、低钾血症性高血压和高雄激素症为特征。我们在9例经典11 β - ohd患者中发现了一种普遍的和三种新的CYP11B1基因突变。对象和方法：招募来自非亲属家庭的11例β - ohd患者9例。11 β - ohd的并发症发生在三名从未接受过糖皮质激素治疗的患者身上。对CYP11B1基因进行了测序，并测定了11种β -羟化酶的体外活性。采用单倍型分析确定携带相同p.R454C突变的受试者的共同祖先。结果：所有患者均发现CYP11B1基因突变，其中常见突变（p.R454C）和3个新突变（p.V148G, IVS7-9C> a, c.1359_1360insG）。p.R141X、p.V148G、c.1359_1360insG和p.R454C突变分别保留了4.9%、3.9%、3.7%和4.5%的残留酶活性。9例患者中有5例携带p.R454C突变，该突变仅在中国11OHD患者中报道。单倍型分析表明，这种突变可能遗传自一个共同的祖先。结论：p.R141X、p.V148G、c.1359_1360insG和p.R454C突变体的酶活性几乎完全消失，符合11 β - ohd的经典形式。1个流行突变和3个新突变的观察结果可能对中国11例β - ohd患者的遗传咨询和产前诊断具有潜在的临床应用价值。(C) 2012 Elsevier Ltd.版权所有。
11 beta-Hydroxylase deficiency (11 beta-OHD), caused by CYP11B1 mutations, is characterized by hyporenine-mic, hypokalemic hypertension and hyperandrogenism. We identified a prevalent and three novel mutations of CYP11B1 gene in nine patients with classic 11 beta-OHD.Subjects and methods: Nine patients with 11 beta-OHD from unrelated families were recruited. The complications of 11 beta-OHD occurred in three patients who never received glucocorticoid treatment. CYP11B1 gene was sequenced and 11 beta-hydroxylase enzymatic activities were assessed in vitro. A haplotype analysis was performed to determine a common ancestor for those subjects who carried the same p.R454C mutation.Results: CYP11B1 gene mutations were identified in all patients, with a prevalent (p.R454C) and three novel mutations (p.V148G, IVS7-9C>A, c.1359_1360insG). The p.R141X, p.V148G, c.1359_1360insG and p.R454C mutations retained 4.9%, 3.9%, 3.7%, 4.5% of residual enzymatic activity, respectively. Five of nine patients carried p.R454C mutation, which was only reported in Chinese 11OHD patients. Haplotype analysis showed that this mutation might be inherited from a common ancestor.Conclusion: The enzymatic activities for p.R141X, p.V148G, c.1359_1360insG and p.R454C mutants were almost completely abolished, which corresponds to classic form of 11 beta-OHD. The observations of a prevalent mutation and three novel mutations might have potential clinical utility for genetic counseling and prenatal diagnosis in Chinese 11 beta-OHD patients. (C) 2012 Elsevier Ltd. All rights reserved.