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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
17α-hydroxylase/17,20 carbon chain lyase deficiency caused by p.Tyr329fs homozygous mutation: Three case reports
Dai Zhang1, Jian-Ran Sun1, Jiang Xu1
1Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China.
Background:
p.Tyr329fs is a cytochrome P450c17 mutation among Chinese individuals. However, data on 17-α-hydroxylase deficiency caused by cytochrome P450c17 p.Tyr329fs homozygous mutation are lacking. This paper is a case report of three patients homozygous for p.Tyr329fs who were diagnosed with 17-α-hydroxylase deficiency between 2005 and 2019.
Case Summary:
Case 1 presented with hypertension, hypokalemia, sexual infantilism and delayed bone age. The patient had a 46, XY karyotype, was homozygous for p.Tyr329fs and was recently treated with dexamethasone 0.375 mg qn. Case 2 presented with hypokalemia, sexual infantilism, osteoporosis and delayed bone age. The patient had a 46, XY karyotype, was homozygous for p.Tyr329fs and was treated with dexamethasone 0.75 mg qn at the last follow-up. Serum potassium and blood pressure could be maintained within normal range for cases 1 and 2. Case 3 presented with amenorrhea, sexual infantilism, osteopenia and delayed bone age. The patient had a 46, XX karyotype, was homozygous for p.Tyr329fs and was treated with dexamethasone 0.75 mg qn and progynova 1 mg qd. Outpatient follow-up revealed an adrenocorticotropic hormone (8 AM) of < 5.00 pg/mL.
Conclusion:
The homozygous p.Tyr329fs mutation usually manifests as a combined deficiency, and definitive diagnosis depends primarily on genetic testing.
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