Association between the genotype and the degree of virilization in girls with classic 21-hydroxylase deficiency / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the association between the CYP21A2 genotype and the virilization severity in girls with classic 21-hydroxylase deficiency (21-OHD), so as to further the understanding of virilization in females and provide guidance for prenatal diagnosis and genetic counseling. Methods:A total of 23 patients with two X chromosomes (46, XX) who were newly diagnosed with classic 21-OHD in Wuhan Children′s Hospital from August 2010 to March 2019 were included.These patients were divided into 3 groups according to the Prader grades of the degree of external genitalia masculinization.The 17-hydroxyprogesterone (17-OHP) level, androstenedione (AND) level, testosterone (T) level, dehydroepiandrosterone sulphate (DHEAS) level and genotypes were recorded.The gene mutations were divided into the Null group(the enzyme activity was completely impaired), group A(1% of the normal enzyme activity was retained), group B(2% of the normal enzyme activity was retained) and group C(20%-60% of the normal enzyme activity was retained). The correlation between the gene variation of different Prader grades and the corresponding gene groups were analyzed.Results:All 23 girls showed different degrees of external genitalia masculi-nization.There was a significant positive correlation between the Prader grades and the type of gene variation ( rs=0.696, P<0.001). The gene group A and Null group were highly matched with the Prader Ⅳ(the matching rate 77.8%). Eighty percent of girls with Prader Ⅱ and Prader Ⅲ were classified as the gene group B. The testosterone le-vel of girls with Prader Ⅳ at first diagnosis was significantly higher than that of girls with Prader Ⅱ [4.6(4.0, 15.0)μg/L vs.0.63(0.40, 1.39)μg/L]( χ2=15.117, P<0.05). Conclusions:There is a significantly positive and strong correlation between the degree of external genitalia masculinization and the degree of deficiency of enzyme activity caused by gene variation in girls with typical 21-OHD.It can provide reference for both parents carrying CYP21A2 gene in prenatal diagnosis, genetic counseling and individualized diagnosis and treatment.