Two novel heterozygous mutations in the CYP17A1 gene in a Chinese patient with 17α-hydroxylase 17,20-lyase deficiency.

Congenital adrenal hyperplasia (CAH) resulting from 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is an uncommon autosomal recessive disease. 17-OHD is caused by mutations in the cytochrome P450c17 gene (CYP17A1), and characterized by hypertension, hypokalemia, female sexual infantilism, or male pseudohermaphroditism. Here we report a case of a 19-year-old Chinese girl (46,XX) with 17-OHD, and analyze her clinical and molecular genetic characteristics. The patient had high blood pressure (147/102 mmHg), irregular menstruation, hypomenorrhea, and normal serum potassium. Physical examination showed that she had normal breasts, armpit hair, pubic hair, and a normal external genital formation. Laboratory investigations revealed low levels of serum cortisol, estradiol, and adrenal androgen, and high levels of adrenocorticotropic hormone (ACTH), progesterone, prolactin (PRL), and renin. However, the levels of blood luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), aldosterone, and aldosterone/rennin (ARR) were normal. Genomic DNA from the patient and her parents was amplified and sequenced. DNA sequence analysis revealed two novel heterozygous mutations (Ile381Thr/Ser168del) in CYP17A1. The novel heterozygous Ile381Thr mutation (c.1142T>C) was detected in the patient's mother, whereas another novel heterozygous Ser168del mutation (c.503_505delCCT) was detected in her father. In conclusion, we discovered two novel heterozygous CYP17A1 mutations Ile381Thr (c.1142T>C) and Ser168del (c.503_505delCCT) in a Chinese patient with 17-OHD.