Identification of steroid biosynthetic defects in genotype-proven heterozygote individuals with 17α-hydroxylase/17,20-lyase deficiency
10.3760/cma.j.issn.1000-6699.2010.08.002
- VernacularTitle:基因型明确的17 α-羟化酶/17,20-裂解酶缺陷症杂合子肾上腺皮质功能的研究
- Author:
Jie QIAO
;
Bingli LIU
;
Jun LIANG
;
Xia CHEN
;
Chunlin ZUO
;
Yanyun GU
;
Jing GONG
;
Jinfeng TANG
;
Yixin WU
;
Yan JIN
;
Yingli LU
;
Wanling WU
;
Huaidong SONG
;
Mingdao CHEN
- Publication Type:Journal Article
- Keywords:
Adrenal glands;
Steroid;
P450c17 deficiency;
Heterozygous;
CYP17A1 gene;
Mutation
- From:
Chinese Journal of Endocrinology and Metabolism
2010;26(8):633-638
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the adrenal steroidogenic function in genotype-proven heterozygotes carrying mutations in CYP17A1 gene in vivo. Methods Eight patients and 14 family members from 5 families with 17-hydroxylase/17,20-lyase deficiency (17OHD) were recruited. The mutations of the CYP17A1 gene in these individuals were screened by direct sequencing of PCR products. The hormonal response to ACTH was evaluated in the 14 genotype-proven carriers and 45 age- and sex-matched normal subjects. Results Three mutations were found in 5 unrelated families. 14 carriers with CYP17A1 mutation were identified, including 7 heterozygotes with D487_F489del, 6 with Y329fs, and 1 for H373L. Compared to the normal subjects, the carriers exhibited lower basal and ACTH-stimulated cortisol levels, but higher ACTH-stimulated corticosterone level. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of normal individuals at baseline and following ACTH-stimulation. Similarly, progesterone level and ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than that of normal individuals before and after stimulation. No significant differences were observed in the hormone levels between two genotypes (D487_F489del vs Y329fs). Conclusions Genotype-proven carriers of 17OHD without apparent clinical symptoms exhibit decreased enzyme activity,analogous to mildly impaired adrenal 21-hydroxylase activity in the carriers of CYP21 A2 gene mutation.
