Clinical and molecular manifestation of fifteen 17OHD patients: a novel mutation and a founder effect

17-hydroxylase deficiency (17OHD) has long been regarded as a rare form of congenital adrenal hyperplasia, inherited in an autosomal recessive pattern. Fifteen patients with 17OHD were described from clinical manifestations and hormone profile. Then, CYP17A1 gene was amplified and sequenced in a new patient. Heterozygous mutations c. 431_433del, p.K144del/c. 985_987delinsAA, p.Y329 fs were identified. Functional study indicated the novel mutation K144del completely abolished enzyme activity. In the three-dimensional model, the K144del mutation completely destroyed the alpha helix in the steroid binding domain. Sixteen SNPs within CYP17A1 gene were selected and genotyped in 7 unrelated families to determine whether Y329 fs had founder effect in China. Haplotyping study showed that all c. 985_987delinsAA mutation shared the same haplotype. However, from GWAS data of 2760 controls, this special haplotype was found only in one chromosome. In conclusion, we identified a novel (K144del) and a widely reported (Y329 fs) heterozygous mutations of CYP17A1 gene from a 17OHD patient. Haplotyping analysis showed the common mutation Y329 fs in China came from the same ancestor, which explains the reason that 17OHD was the second cause of CAH in China.