Phenotypic variation in a Chinese family with 46,XY and 46,XX 17α-hydroxylase deficiency.

BACKGROUND: 17α-hydroxylase deficiency is a rare autosomal recessive disorder characterized by sexual infantilism, amenorrhea, hypertension and hypokalemia, which is caused by mutations in the CYP17A1 gene. To date, more than 50 mutations in this gene have been described.

METHODS: The clinical features and biochemical data of a pair of 46,XY and 46,XX Chinese siblings with 17α-hydroxylase deficiency from Singapore were studied. Direct DNA sequence analysis of the CYP17A1 gene was performed.

RESULTS: There was significant phenotypic variation between the siblings. The proband (46,XY) presented classically with sexual infantilism, amenorrhea and hypertension. The younger sibling (46,XX) also presented with amenorrhea, but she had breast development and absence of hypokalemic hypertension. The same compound heterozygous mutations in CYP17A1 gene were identified in both patients. A missense mutation (P409R) was detected in exon 7, and a 9-bp deletion (D487-S488-F489del) was detected in exon 8.

CONCLUSION: We confirmed the diagnosis of 17α-hydroxylase deficiency in these two patients. Both P409R and D487-S488-F489del have been described previously and are widely propagated in the Chinese population in East and Southeast Asia. We propose that the phenotypic expression of affected individuals with 17α-hydroxylase deficiency is karyotype-dependent, with individuals having the 46,XX karyotype having less pronounced clinical symptoms.