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Phenotypic heterogeneity and fertility potential of patients with 17-hydroxylase/17,20-lyase deficiency

Journal of Clinical Endocrinology and MetabolismXu Y, Jiang S, Yan Z, et al. | January 24, 2022


Analyzing the clinical features, phenotype heterogeneity, genotyping and the likelihood of pregnancy of patients with 17OHD (17α-Hydroxylase/17,20-lyase deficiency), it was found that partial 17OHD gives rise to nonclassical clinical features, without hypertension and hypokalemia. Appropriate choice of ovulation induction regimen, precise dose of glucocorticoid to reduce progesterone levels, and the use of IVF-ET could allow successful pregnancy in such 46,XX patients.

  • In nonclassical patients, genotype analysis was conducted, and through in vitro enzyme activity assays and three-dimensional structure observations, the function of 3 missense mutations of the CYP17A1 gene was assessed.

  • In 13 patients, eight mutations were found, including the homozygous mutation p. N395D and p. R496C, compound heterozygous mutation p. Y329fs/p. A421A and p. I332T/p. D487_F489del in 4 nonclassical patients.

  • An in vitro functional analysis demonstrated mild impairment of 17α-hydroxylase activities 15.3-25.0% but residual 17,20-lyase activities 6.6%-9.4%, for the three missense mutations.

  • The combined progestin-primed ovarian stimulation, IVF-ET and the use of low-dose dexamethasone resulted in successful pregnancy in two 46,XX females.

  • Birth of a healthy baby was successfully achieved in one case.