基础医学与临床 ›› 2009, Vol. 29 ›› Issue (3): 225-228.

• 研究论文 •    下一篇

1例17α-羟化酶/17, 20碳链裂解酶缺陷症的临床和分子遗传分析

曹彩霞 王鸥 聂敏 李玉秀 童安莉 卢琳 陆召麟   

  1. 中国医学科学院北京协和医学院北京协和医院内分泌科 中国医学科学院北京协和医学院北京协和医院内分泌科 中国医学科学院北京协和医学院北京协和医院内分泌科 中国医学科学院北京协和医学院北京协和医院内分泌科 中国医学科学院北京协和医学院北京协和医院内分泌科 中国医学科学院北京协和医学院北京协和医院内分泌科
  • 收稿日期:2008-04-23 修回日期:2008-06-06 出版日期:2009-03-25 发布日期:2009-03-25
  • 通讯作者: 聂敏

Clinical and Molecular Genetic Analysis on a Patient with 17 Hydroxylase /17, 20 Lyase Deficiency

Cai-xia CAO, Ou WANG, Min NIE, Yu-xiu LI, An-li TONG, Lin LU, Zhao-lin LU   

  1. Department of Endocrinology, Key laboratory of Ministry of Health, PUMC Hospital, CAMS & PUMC Department of Endocrinology, Key laboratory of Ministry of Health, PUMC Hospital, CAMS & PUMC Department of Endocrinology, Key laboratory of Ministry of Health, PUMC Hospital, CAMS & PUMC Department of Endocrinology, Key laboratory of Ministry of Health, PUMC Hospital, CAMS & PUMC Department of Endocrinology, Key laboratory of Ministry of Health, PUMC Hospital, CAMS & PUMC Department of Endocrinology, Key laboratory of Ministry of Health, PUMC Hospital, CAMS & PUMC
  • Received:2008-04-23 Revised:2008-06-06 Online:2009-03-25 Published:2009-03-25
  • Contact: Min NIE,

摘要: 目的 通过对1例17α-羟化酶/17,20碳链裂解酶缺陷症(17OHD)患者的临床特点和基因突变研究,初步探讨17OHD临床表现的基因分子机制。方法 收集患者临床资料,提取患者外周血白细胞DNA,PCR扩增CYP17A1基因的8个外显子及内含子边界,测序确定CYP17A1基因的突变位点。结果 患者临床表现及内分泌功能检查完全符合17OHD,PCR产物测序发现, CYP17A1基因第6外显子329位密码子发生了TAC→AA的纯合突变,引起Tyr329Lys错义突变及以后密码子的移码突变,并形成了一个只包含418个氨基酸的截短蛋白,从而使该蛋白完全缺乏17α-羟化酶和17,20碳链裂解酶活性。 结论 CYP17A1突变导致的P450c17蛋白的结构改变是该17OHD患者临床表现的基因分子基础。

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 a Chinese patient with 17α- hydroxylase/17, 20 Lyase deficiency(17OHD). Methods Clinical features and laboratory data were collected . Genomic DNA was extracted from leukocytes of peripheral blood of the patient. All eight exons of the CYP17 gene, including the flanking regions of introns, were amplified by PCR. The mutations of the CYP17A1 gene were analyzed by direct sequencing the amplified DNA fragments. Results The patient was diagnosed as 17OHD according to the clinical presentations , laboratory examinations and CYP17A1 mutation which was identified as a base deletion and a base transversion ( TAC/AA) at codon 329 and caused a missense mutation of Tyr→Lys at this codon and the open reading frame shift following this codon to produce a truncated enzyme without activity site. Conclusions Through CYP17A1 gene mutation analysis, the clinical diagnosis of 17OHD was confirmed . The alternation of P450c17 structure caused by CYP17A1 gene mutation is the molecular mechanisms of clinical manifestation of the patient.

Key words: 17α- hydroxylase/17, 20 Lyase deficiency, CYP17A1, Mutation

中图分类号: