Analysis of CYP21A2 gene mutation and phenotype in patients with 21-hydroxylase deficiency
10.3760/cma.j.issn.1000-6699.2019.01.004
- VernacularTitle:21-羟化酶缺乏症CYP21A2基因突变及表型分析
- Author:
Jianbo SHU
1
;
Xinjie ZHANG
;
Xiaowei XU
;
Qianqian ZOU
;
Chao WANG
;
Yingtao MENG
;
Chunquan CAI
;
Shuxiang LIN
;
Le HUANG
;
Ling LYU
Author Information
1. 天津市儿童医院天津市儿科研究所 300134
- Keywords:
21-Hydroxylase deficiency;
CYP21A2 gene;
Mutation
- From:
Chinese Journal of Endocrinology and Metabolism
2019;35(1):21-25
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the spectrum of CYP21A2 gene mutation and the correlation between genotype and phenotype in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas.Methods Genomic DNA was extracted from the peripheral blood samples of the proband.Locus-specific PCR,direct sequencing of PCR amplification products,and multiplex ligation-dependent probe amplification were applied to detect pathogenic gene CYP21A2 and the relationship between genotypes and phenotypes was analyzed.Results (1) Of 35 patients with 21-hydroxylase deficiency,25 were classified as salt-wasting phenotype and 10 were simple virilizing phenotype.(2) 69 mutant alleles were detected in a total of 70 alleles in 35 patients.Only one mutant allele was detected in one patient.Two mutant alleles were detected in all other patients,with the mutation detection rate 98.6％.(3) A total of 6 types of mutations were detected,of which c.293-13C/A＞G (I2G) was the most common,accounting for 57.1％ (40/70),followed by 18.6％ (13/70) for large gene deletion or conversion,and 14.3％ (10/70) for p.I173N.In addition,a novel mutation,c.949C＞T (p.R317X),which has not been reported previously,was detected as a pathogenic mutation.(4) Correlation analysis of genotype and phenotype in 35 children showed that the phenotype predicted by genotype was consistent with the actual salt-wasting phenotype in 31 children,and those in three children were inconsistent with the actual clinical phenotype.Conclusion The mutation characteristics of CYP21A2 gene in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas are slightly different from those reported in other regions in China.A mutation c.949C＞T has not been reported,which enriches the mutation spectrum of CYP21A2 gene and provide the foundation for genetic counseling and prenatal diagnosis.
