Identification of a novel compound heterozygous mutation of the CYP21A2 gene causing 21-hydroxylase deficiency in a Chinese pedigree

21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia. Inherited in an autosomal recessive manner, 21-OHD is caused by mutations in the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene. The present study was designed to investigate the genetic characteristics of one Chinese pedigree and to identify the genotype-phenotype association, thereby facilitating the precise diagnosis of 21-OHD at the molecular level. Members of a Chinese family with 21-OHD were screened for mutations in the CYP21A2 gene. Clinical data and biochemical parameters, including androgen and derivatives, were collected. Complete DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were utilized to analyze the genetic variations in the full-length CYP21A2 gene. A C-T transition located in exon 8 of the CYP21A2 gene, leading to the predicted amino acid residue change from Arg to Trp at codon 342, was identified in the mother and four sisters. Additionally, heterozygous deletion mutations of exons 1, 3, 4, 6 and 7 of paternal origin were detected in the four sisters by MLPA analysis. During the one-year follow-up, the four sisters exhibited symptom improvement following treatment with glucocorticoids, and the proband and one sister successfully conceived. The results of the present study demonstrated that novel compound heterozygous variations in the CYP21A2 gene may be causative agents of 21-OHD, providing insights into the functions of this gene and a more comprehensive understanding of the disorder.