A new compound heterozygous mutation in theCYP17A1gene in a female with 17α-hydroxylase/17,20-lyase deficiency

Background: Congenital adrenal hyperplasia due to 17α-hydroxylase/17,20-lyase deficiency (OMIM #202110) is a rare autosomal recessive disorder, which is caused by mutations of the CYP17A1 gene located on chromosome 10q24.3. It has been reported that the type of mutation of the CYP17A1 gene was associated with the extent of 17α-hydroxylase/17,20-lyase deficiency, and the prevalence of common mutation was different among ethnic groups.Case: A 21-year-old Korean female presented with primary amenorrhea and sexual infantilism, and intermittent hypokalemic episodes. Laboratory test was consistent with hypergonadotropic hypogonadism. The karyotype was 46,XX[20]. Genomic DNA was extracted from peripheral blood leukocytes. All the eight exons of the CYP17A1 gene including flanking regions of introns were amplified by PCR. The mutations of the CYP17A1 gene were detected by direct sequencing. A compound heterozygous mutation was identified; one allele had a missense mutation of c.1118A>T (p.His373Leu), which was reported previously and induced the complete loss of both 17α-hydroxylase/17,20-lyase activity. This mutation has been known to be one of the common mutation types in East Asia. The other allele had a novel 1-bp deletion c.1148delA causing frameshift, premature termination codon (p.Glu383fs) and induced truncated enzymes.Conclusion: Our experience for stepwise clinical, laboratory and molecular approach would be helpful to diagnose these patients accurately and understand the genetic events in 17α-hydroxylase/17,20-lyase deficiency patients.