The New Mutation Of CYP21A2 Gene And Congenital Adrenal Hyperplasia:A Case Report

Background:Congenital adrenal hyperplasia?CAH?is a group of autosomal recessive diseases,which is one of the most common hereditary endocrine diseases.This disease is due to deficiency of certain enzyme in congenital steroidal hormonal biosynthesis,with a variety of clinical manifestations.The common forms of CAH are caused by deficiency in 21-hydroxylase enzymes,11?-hydroxylase,3?-steroid dehydrogenase,17a-hydroxylase,and so on,among which 21-hydroxylase deficiency is the most common form,accounting for about 95%of CAH cases.The 21-hydroxylase is encoded by a gene named CYP21A2.CYP21A2 locates on the short arm of chromosome 6?6p21.3?in human leukocyte antigen ? gene region,which consists of inactived CYP21A1?pseudogene?and actived CYP21A2?true gene?.Pseudogene and true gene have the same number of exons and introns?ten and nine respectively?,with homologies of 98%and 95%respectively.This study aimed to reveal the mutation sites and their origins of a patient who was diagnosed with 21-hydroxylase deficiency and her parents and older sister,and then to explore the molecular genetic basis of 21-hydroxylase deficiency.Subjects and methods:This patient was a six-year-old girl who was admitted to our hospital for surgery because of malformation of external genitalia.Primers for PCR were designed according to the sequences of CYP21A2 in gene database to amplify the ten exons and the boundary sequences of the patient,her parents and her older sister.The PCR products were sequenced.The sequencing results were compared to CYP21A2 in normal subjects.Results:By comparing the sequencing results and chromatograms with the reference sequences in normal subjects,we found that there were two compound heterozygous mutations in the CYP21A2 of patient.They were at position 6118,heterozygous A replaced T?NG₀07941.2:g.6119T>A?and at position 6698,heterozygous A deleted?NG₀07941.2:g.6699de1A?.Heterozygous g.6119T>A and heterozygous g.6699delA mutations were found in her mother and father respectively.Heterozygous g.6119T>A and heterozygous g.6699delA mutation were also found in her sister,who was diagnosed with CAH and had clitoroplasty.The g.6119T>A mutation is a known mutation in patients with CAH,while g.6699delA is novel mutation.Conclusions:This study identified two compound heterozygous mutations of CYP21A2.The g.6699delA mutation had not been reported so far,which is worthy of further study.