Correlation Analysis Of Genotype And Clinical Phenotype Of 21-hydroxylase Deficiency In Shanxi Province

Objective:(1)Analysis of 21-hydroxylase deficiency(21-OHD)in children with clinical features andrelated biochemical examination,improve the understanding and diagnosis of this disease.(2)To investigate gene mutations in children with 21-hydroxylase deficiency(21-OHD)in Shanxi province.(3)Study of the gene sequencing results of 21-OHD children,to explore the relationshipbetween genotype and clinical phenotype,and to provide basis for prenatal diagnosis and genetic counseling.Methods:(1)Retrospective analysis of the clinical data of Shanxi nationality patients with 21-OHD in children's Hospital of Shanxi from October 2014-October2016.The clinical features and laboratory examinations of 21-OHD were summarized.(2)CYP21A2 gene mutation was analyzed by Sanger sequencing and other molecular biological techniques in 21-OHD children.(3)To analyze the CYP21A2 gene detection results and compare with the clinical classification,and to analyze the correlation between genotype and clinical phenotype.Results:(1)The clinical features and biochemical indexes of 21-OHD children: in this group,there were 15 cases,all Classic type,which include 8 cases of Salt losing type(SW),7 cases of simple virilizing(SV).Among them 7 caseshospitalized with adrenal crisis,boys over the age of 2hospitalized with precocious puberty,masculine sign.girlswere born with genital ambiguity.3 cases of SV with true precocious puberty,follicle stimulating hormone(FSH),luteinizing hormone(LH)significantly increased.17-OHP,ACTH were increased in different degrees;sodium ions in most children were decreased;but potassium normal or even decreased.(2)CYP21A2 gene test results: a total of 7 mutations were detected in 15 cases,including IVS2-13A/C>G,I172 N,R356W,E3? 8bp,c.1064G>A,c.141C>A,c.121C>T.the most common mutation was IVS2-13A/C>G(40%),and the other common mutations were R356W(16.7%),I172N(16.7%)and E3?8bp(6.7%).the most common mutations in SWCAH were IVS2-13A/C>G and R356 W,the allele frequencies were 50% and 18.8%.The most common mutation in SVCAH patientswas I172 N,and the allele frequency was 35.7%.(3)The correlation between genotype and clinical phenotype: the overall correlation between genotype and clinical phenotype was larger,the positive predictive value of genotype and clinical phenotype in SW,SV were 87.5%,100%.Conclusion:(1)The most common type of 21-OHD was classic type.Salt losing type often with vomiting,antifeedant,weight does not increase or decrease,electrolyte disorder treatment,seroiu person suffer from life-threatening;simple virilizing,female children often manifested aspseudohermaphroditism;children with precocious puberty,often with masculine signs,if not diagnosed in time,will develop into true precocious puberty.Biochemical indicators of 17-OHP,ACTH increased,combined with clinical manifestations can be diagnosed.(2)The IVS2-13A/C>G,R356 W and I172 N detected in this study were common mutations,and the hot spot mutation in Shanxi province was IVS2-13A/C>G.(3)There was a significant correlation between genotype and clinical phenotype,especially in patients with classical type,and the the genotype-phenotypecorrelation between thesalt wasting phenotype and simple virilizing typewere 87.5% and 100%,respectively.