New, recurrent, and prevalent mutations: Clinical and molecular characterization of 26 Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency

Abstract Background Combined 17alpha-hydroxylase/17,20-lyase deficiency (17OHD), caused by mutations in the CYP17A1 gene, is a rare autosomal recessive form of congenital adrenal hyperplasia and characterized by hyporeninemic hypokalemic hypertension, primary amenorrhea and absence of secondary sexual characteristics. Subjects and methods Twenty six 17OHD subjects from 23 Chinese families were recruited. The CYP17A1 gene was sequenced and 17alpha-hydroxylase/17,20-lyase enzymatic activities were assessed in vitro. Results Eight CYP17A1 mutations were identified in 23 patients. Of eight mutations, c.985-987delinsAA/p.Y329Kfs and c.1460-1469del/p.D487-F489del mutations accounted for 60.8% (28/46) and 21.7% (10/46) of the mutant alleles, respectively. The enzymatic activities for both mutations were completely abolished. We also identified three novel mutations c.971-972insG/p.K325Afx, c.1464-1466delT/p.F489Sfx and c.1386G>T/p.R462S. The enzymatic activities for c.971-972insG/p.K325Afx and c.1464-1466delT/p.F489Sfx mutations were almost completely abolished, whereas the mutation c.1386G>T/p.R462S only resulted in partial reduction of 17alpha-hydroxylase (34.6%) and 17,20 lyase activities (27.0%), which is correlated with the partial 17OHD phenotype in this patient. Conclusion The c.985-987delinsAA/p.Y329Kfs and c.1460-1469del/p.D487-F489del mutations are prevalent in Chinese 17OHD patients. The genetic defects are well correlated with the phenotypes in both complete and partial forms of 17OHD.