Yanase T
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):153-7. doi: 10.1016/0960-0760(95)00029-y.
Congenital adrenal hyperplasia due to 17 alpha-hydroxylase/17/20-lyase deficiency is caused by genetic defects in the gene encoding P450c17 (CYP17). To date, 18 different mutations in 27 individuals have been identified and all of them are located in the coding region of CYP17. Several mutations have been reconstructed in human P450c17 cDNA and expressed in COS cells to characterize the kinetic properties of 17 alpha-hydroxylase and 17,20-lyase activities. The molecular bases of cases clinically reported as 17 alpha-hydroxylase deficiency have turned out to result from complete or partial combined deficiencies of 17 alpha-hydroxylase/17,20-lyase. The elucidation of the molecular bases generally explains the patient's clinical profiles including the sexual phenotype of the external genitalia. In one case initially reported as isolated 17,20-lyase deficiency, the molecular basis was found to be partial combined deficiency of both activities, somewhat discordant with the patient's clinical profile. However, the patient was subsequently found to have 17 alpha-hydroxylase deficiency, suggesting involvements of age-dependent unknown factors affecting P450c17 activity.
由17α-羟化酶/17,20-裂解酶缺乏引起的先天性肾上腺皮质增生症是由编码P450c17（CYP17）的基因中的遗传缺陷所致。迄今为止，已在27名个体中鉴定出18种不同的突变，所有这些突变均位于CYP17的编码区域。已在人P450c17 cDNA中重建了几种突变，并在COS细胞中表达，以表征17α-羟化酶和17,20-裂解酶活性的动力学特性。临床上报告为17α-羟化酶缺乏症病例的分子基础已证明是由17α-羟化酶/17,20-裂解酶的完全或部分联合缺乏所致。分子基础的阐明通常解释了患者的临床特征，包括外生殖器的性表型。在一例最初报告为孤立性17,20-裂解酶缺乏症的病例中，发现分子基础是两种活性的部分联合缺乏，这与患者的临床特征有些不一致。然而，该患者随后被发现患有17α-羟化酶缺乏症，提示年龄依赖性未知因素影响P450c17活性。
