Genotype-phenotype correlation in 27 pediatric patients in congenital adrenal hyperplasia due to 21-hydroxylase deficiency in a single center

PURPOSE The purpose of the study was to evaluate endocrine patterns of patients with congenital adrenal hyperplasia and each gene mutation and to analyze the correlation between each phenotype and genotype. METHODS This was a retrospective study of the patients with congenital adrenal hyperplasia in the pediatric outpatient clinic at the Samsung Medical Center from November 1994 to December 2012. We analyzed the medical records of 27 patients (male, 19; female, 8) with congenital adrenal hyperplasia who had been diagnosed by genetic testing to have 21-hydroxylase deficiency. RESULTS In genetic analysis of 54 alleles from 27 patients, 13 types of mutations were identified. The distribution of 21-hydroxylase deficiency gene mutations revealed that intron 2 splice site (c.293-13A/C>G) mutations and large deletions were the most common, at 31.5% and 22.2% respectively, followed by p.I173N, p.R356W, and p.I172N mutations at 11.1%, 9.3%, and 9.3%, respectively. Other mutations were observed at 1.9-3.7%. No novel mutations were detected. CONCLUSION The analysis of 54 alleles revealed 13 types of mutation. The salt wasting form showed a good correlation between genotype and phenotype, but the simple virilizing and nonclassic forms showed inconsistencies between genotype and phenotype. The distribution of CYP21A2 mutations was evaluated for 21-hydroxylase deficiency patients from a single center. This study provides limited data on mutation spectrum and genotype-phenotype correlation of 21-hydroxylase deficiency in Korea.