Analysis of the phenotypes and genotypes of patients with 21-hydroxylase deficiency in Xuzhou

Objective To analyze the mutation frequency of genotypes and phenotypes of children with 21-hydroxylase deficiency (21-OHD) in Xuzhou, and investigate the phenotype-genotype correlation of these patients. Methods A total of 16 21-OHD patients who were admitted into Xuzhou Maternity and Child Health Care Hospital from June 2016 to June 2019 were enrolled and their clinical data were retrospectively analyzed. Their 21-hydroxylase encoding gene CYP21A2 was detected by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) and the relationship between the phenotypes and genotypes was analyzed. Results Two mutated alleles were detected in each of the 16 patients, with a total of 8 types of mutation sites which were known to be lethally mutated, namely c.293-13C>G, c.518T>A, Exon1-7del, Exon1-3del, c.1451_1452delinsC, c.1333C>T, E6 Cluster, and c.1273G>A. Notably, c.1333C>T has not been reported among domestic Chinese populations. All the mutation was inherited from child patients' parents, where the mutation with the highest mutation frequency was c.293-13C>G (33.1%), followed by c.518T>A (28.1%) and Exon1-7del (15.6%). Among these patients, there were 8 children whose genotype was predicted as salt wasting (SW) form, with a consistent rate of 100% with their actual phenotypes. Furthermore, there were another 8 children whose phenotypes was predicted as simple virilizing (SV) form, with a consistent rate of 87.5% with their actual phenotypes in 7 children. Conclusions The 21-OHD children in Xuzhou are SW or SV form, with the common mutation sites of c.293-13C>G, c.518T>A, and Exon1-7del. Their predicted genotypes are well consistent with their actual phenotypes.