复合杂合突变致部分性17α-羟化酶／17，20碳链裂解酶缺陷症的临床和遗传分析

A compound heterozygous mutation in CYP17A1 gene in a female subject with partial 17α- hydroxylase/17,20 lyase deficiency

目的通过对1例部分性17α-羟化酶／17，20碳链裂解酶缺陷症（170HD）的女性患者及其母亲的临床特点和基因突变研究，初步探讨部分性170HD患者临床表现的基因分子生物学机制。方法收集患者临床资料，提取患者及其母亲的外周血白细胞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。结果患者临床表现为高血压及轻度低钾血症，有不规律月经，CYP17A1基因序列分析发现患者为复合杂合突变，其中1个等位基因突变为编码P450c17蛋白的53或54位苯丙氨酸的密码子TTc缺失，即Delp．53／54F；另1个等位基因突变为编码329位氨基酸的密码子由TAC变成从，使酪氨酸变为赖氨酸，之后的序列发生移码突变并提前终止，产生截短蛋白，即P．Y329K，418X。患者母亲是携带P．Y329K，418X突变的杂合子。结论CYP17A1基因的复合杂合突变是该部分性170HD患者临床表现的基因分子基础。

Objective To explore the clinical and molecular genetic characteristics of a Chinese female patient with partial 17α- hydroxylase/17, 20 lyase deficiency （170HD）, a rare type of congenital adrenal hyperplasia. Methods Her clinical features and laboratory data were collected. Genomic DNA was extracted from leukocytes of peripheral blood of her and her mother. All eight exons of CYP17A1 gene, including flanking regions of introns, were amplified by PCR. The mutations of CYP17A1 gene were identified by direct sequencing or cloning and sequencing the amplified DNA fragments. Results The patient presented with hypertension, hypokalemia and irregular menstruation. DNA sequencing results demonstrated a compound heterozygous mutation in CYP17A1 gene. One allele of her had the deletion of phenylalanine （TYC） at either codon 53 or 54 and the other allele contained a base transversion at codon 329 （TAC/AA） and leading to a missense mutation of tyrosine to lysine and the open reading frame shift following this codon to produce a truncated enzyme with 417 amino acids and without activity site. Her mother was a heterozygous carrier of the latter allele. Conclusion The partial 170HD in this patient is caused by a compound heterozygous mutation in CYP17A1 gene.