Genetic analysis and novel variation identification in Chinese patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency is an autosomal-recessive disorder caused by mutations in the CYP21A2 gene. The aim of the study was to analyze the molecular data of 155 21-OHD patients and retrospectively investigated the common allelic mutations of CYP21A2 in 1442 Chinese 21-OHD patients. Clinical features and mutations of CYP21A2 gene in 155 unrelated 21-OHD patients were examined. Of the 155 patients, 103 cases were salt-wasting (SW) forms, 38 were simple virilizing (SV) forms and 14 were non-classical (NC) forms. In general, two types of mutations including common allelic mutations (281/310, 90.6%) and rare mutations (29/310, 9.4%) were detected, among them four novel variants c.835G>T, c.1081C>T, c.1423C>T and c.651 + 2 T > G were identified. In 1442 Chinese 21-OHD patients, the most frequently mutations were I2G (36.2%), large deletion/conversion (20.7%) and p.I173N (17.8%), while p.V282L has the lowest frequency. In this study, we provided detailed clinical data and mutation spectrum in Chinese 21-OHD patients. Moreover, four novel CYP21A2 variants (c.835G>T, c.1081C>T, c.1423C>T and c.651 +2 T > G) were identified and computational structural modeling indicated that these novel variations probably affect structural stability. Our findings improve the understanding of CYP21A2 mutational spectrum and contribute to the precise diagnosis and prenatal counseling.