Phenotypical And Molecular Characteristics Of46,Xy Disorder Of Sex Development(46,XY DSD)

Objective: To explore the clinical and genetic features of 46,XY disorder of sex development(46 XY,DSD)by analyzing the relative data of 16 patients.Patients and methods: Clinical and biochemical characteristics in 16 cases from 14 unrelated families are described.According to clinical diagnosis,genotyping analysis of SRD5A2 or AR(Androgen Receptor)was performed in each patient.The deleterious effects of three novel mutations of SRD5A2 were assessed by mutagenesis,transfection and in-vitro enzymatic activity assay.Results: Sixteen patients present with microphallus,hypospadias and cryptorchidism,were diagnosed as 5?-reductase 2 deficiency(5?-RD2)and complete androgen receptor deficiency(CAIS).Fourteen SRD5A2 gene mutations were identified in thirteen patients and three have never been reported(p.K35 N,p.H162 P and p.Y136X).It was demonstrated that the nonsense mutation p.Y136 X abolished enzymatic activity,whereas p.H162 P and p.K35 N affected activity moderately.The p.Q6 X,one of the prevalent mutations,was not a founder gene effect in Chinese population.In addition,two mutations of AR gene were identified in 3 patients with CAIS.Conclusion: Our study describes the clinical and genetic characteristics of 16 patients with 46,XY DSD.The deleterious effects of three novel mutations of SRD5A2 gene were explored.We expand the mutations of SRD5A2 in the Chinese population.Clinical management of this disease requires early and accurate diagnosis,especially genetic diagnosis.