10例17α羟化酶/17,20碳链裂解酶缺陷症临床和遗传学研究

Clinical and Genetic Analysis for 10 Patients with 17α Hydroxylase/17, 20 Lyase Deficiency

目的回顾10例17α羟化酶/17,20碳链裂解酶缺陷症(17OHD)患者的资料,分析17OHD的临床特征和分子遗传学特点。方法收集患者临床、基础激素测定和影像学检查资料,对患者及其直系亲属的基因型采用PCR扩增产物直接测序方法明确;对于杂合突变,采用亚克隆方法进一步明确。结果10例患者均存在第二性征不发育、高血压、低血钾;基础激素测定示睾酮、雌二醇、17羟孕酮、皮质醇明显低于正常,而促性腺激素和促肾上腺皮质激素反馈性增高,双侧肾上腺增生。基因诊断共检测到5种基因型;替代和缺失的复合突变占80%;其中D487_F489del3个氨基酸的缺失累及到了4个家系7例患者(70%),共有45%的等位基因受累,是频率最高的突变。结论对于第二性征不发育的患者,应注意该病的鉴别诊断;D487_F489del是中国人的17OHD最常见的突变类型。

Objective To analyze the clinical and lase/17,20 lyase deficiency （17OHD）. Methods genetic characteristics of 10 Chinese patients with 17α hydroxyClinical features and laboratory data were collected from 7 kindreds with 17OHD. PCR products and subclone sequencing were performed to screen the mutation of CYP17A1 gene. Results All patients had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. The laboratory examinations indicated decreased plasma cortisol, 17-hydroxy progesterone, estradiol and testosterone, and elevated blood adrenocorticotrophic hormone （ACTH）, follcie-stimulating hormone （FSH） and luteinizing hormone （LH）. CT scan showed bilateral adrenal hyperplasia. 5 CYP17A1 mutations were identified, 4 of which are novel types D487_F489del, the most frequent mutation, was identified in 4 families and 45% alleles. Conclusion Our study indicates that 17OHD should be considered in the diagnosis of patients with sexual infantilism. D487_F489del is the most frequent mutation in Chinese 17OHD patients.