上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（临床研究） • 上一篇    下一篇

2例17α-羟化酶/17,20碳链裂解酶缺陷症患者临床及遗传学分析

虎子颖，赵志刚，汪艳芳，袁慧娟，张会峰，郑瑞芝   

  1. 郑州大学人民医院（河南省人民医院）内分泌科， 郑州 450003
  • 出版日期:2015-03-28 发布日期:2015-03-26
  • 通讯作者: 赵志刚, 电子信箱: zhaozhigang1957@126.com。
  • 作者简介:虎子颖(1973—)， 女， 回族， 副主任医师， 博士; 电子信箱: huziying828@126.com。
  • 基金资助:

    河南省基础与前沿研究计划项目（142300410071）

Clinical and genetic analysis of two patients with 17α-hydroxylase/17,20-lyase deficiency

HU Zi-ying, ZHAO Zhi-gang, WANG Yan-fang, YUAN Hui-juan, ZHANG Hui-feng, ZHENG Rui-zhi   

  1. Department of Endocrinology, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
  • Online:2015-03-28 Published:2015-03-26
  • Supported by:

    Henan Province Basic and Frontier Research Project, 142300410071

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摘要：

目的 分析2例17α-羟化酶/17,20碳链裂解酶缺陷症患者的临床特点和分子遗传学特征。方法 收集2007年9月—2008年7月在河南省人民医院内分泌科治疗的2例患者临床、基础激素测定和影像学检查资料，对患者进行CYP17A1基因检测。结果 2例患者血压高于正常值，血钾低于正常值，第二性征发育不良。激素测定示血皮质醇水平低于正常，促肾上腺皮质激素反馈性增高；肾素活性受抑制；睾酮、雌二醇低于正常值，而促性腺激素增高。CT示双侧肾上腺增生。CYP17A1基因检测显示, 2例患者基因第6外显子上发现c.1 045del和c.1 047C>A，329位密码子发生了TAC-AA纯合突变，引起Tyr329Lys错义突变及以后密码子的移码突变，并提前产生一个终止密码子(418TGA)。结论 高血压伴低血钾患者同时存在性发育不良，应考虑17α-羟化酶缺陷症的可能，CYP17A1基因突变导致的P450c17蛋白的结构改变是17α-羟化酶缺陷症的分子基础。

关键词: 17α-羟化酶/17,20碳链裂解酶缺陷症, CYP17A1基因, 突变

Abstract:

Objective To analyze the clinical and molecular genetic characteristics of 2 patients with 17α-hydroxylase/17, 20-lyase deficiency. Methods Clinical data and data of basal hormone determinations and imaging examinations of two patients who were treated at the Department of Endocrinology, People's Hospital of Zhengzhou University from September 2007 to July 2008 were collected and CYP17A1 gene of patients were detected. Results The 2 patients had typical clinical presentations of hypertension, hypokalemia, and sexual infantilism. Hormone determination revealed that the blood cortisol level was below the normal, the feedback effect of adrenocorticotropic hormone (ACTH) increased, the activity of renin was inhibited, testosterone and estrogen levels were significantly lower than the normal, and the gonadotropin level increased. CT scan showed bilateral adrenal hyperplasia.  Detection of CYP17A1 gene revealed that there was a compound mutation c.1 045del and c.1 047C>A in the exon 6 of CYP17A1 gene of the two patients, which resulted in a base deletion and a base transversion (TAC/AA) at codon 329, caused a missense mutation of Tyr-Lys and the open reading frame shift following this codon, and produced a termination codon 418TGA in advance. Conclusion For patients with hypertension, hypokalemia, and dysplasia, the possibility of 17 alpha-hydroxylase deficiency should be considered. The alternation of P450c17 structure caused by the mutation of CYP17A1 gene is the molecular basis of 17α-hydroxylase deficiency.

Key words: 17α-hydroxylase/17,20-lyase deficiency, CYP17A1 gene, mutation