Molecular modeling and clinical characterization of a CYP17A1 variant (p.Asp298Asn) causing 17α-hydroxylase/17,20-lyase deficiency in two siblings

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases resulting from defects in enzymes involved in steroidogenesis. One of the rare causes of CAH, 17α-hydroxylase/17,20-lyase deficiency, occurs due to pathogenic variants in the CYP17A1 gene. The CYP17A1 gene encodes the enzymes 17α-hydroxylase and 17,20-lyase which play critical roles in steroidogenesis and androgenesis. (1) This case report presents a previously uncharacterized homozygous variant, c.892G>A(p.Asp298Asn), in the CYP17A1 gene (NM_000102.4), classified as “likely pathogenic” according to ACMG criteria, detected in two siblings diagnosed with 17α-hydroxylase/17,20-lyase deficiency.