In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 6 ( 2022-05-17), p. e2610-e2618
Abstract:
17α-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by a human CYP17A1 gene mutation and has the classical phenotype of hypertension, hypokalemia, sexual infantilism, and primary amenorrhea in females (46,XX) and disorders of sexual development in males (46,XY). To date, few cases of 17OHD have been reported, and the likelihood of pregnancy has rarely been explored. Objective To study the clinical characteristics, phenotype heterogeneity, genotyping, and the likelihood of pregnancy of patients with 17OHD. Design Genotype analysis was performed by direct sequencing of the CYP17A1 gene and next-generation sequencing in nonclassical patients. In vitro enzyme activity assays and 3-dimensional structure observations were used to assess the function of 3 missense mutations of the CYP17A1 gene. Progestin-primed ovarian stimulation (PPOS) was chosen for ovulation induction in 2 patients. Results Eight mutations were identified from 13 patients, including the homozygous mutations p. N395D and p. R496C and compound heterozygous mutations p. Y329fs/p. A421A and p. I332T/p. D487_F489del in 4 nonclassical patients. For the 3 missense mutations, an in vitro functional study showed mild impairment of 17α-hydroxylase activities 15.3-25.0% but residual 17,20-lyase activities 6.6%-9.4%. Two 46,XX females succeeded in pregnancy and delivery by combined PPOS, in vitro fertilization embryo transfer (IVF-ET), and the use of low-dose glucocorticoids. Conclusions Partial 17OHD present nonclassical clinical features, without hypertension and hypokalemia. Successful pregnancy in such 46,XX patients could be attained by the appropriate choice of ovulation induction regimen, precise dose of glucocorticoid to reduce progesterone levels, and the use of IVF-ET.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/clinem/dgac029
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2022
detail.hit.zdb_id:
2026217-6
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