In this study,we investigated the genetics,clinical features,and therapeutic approach of 14 patients with 5a-reductase deficiency in China.Genotyping analysis was performed by direct sequencing of PCR products of the ...In this study,we investigated the genetics,clinical features,and therapeutic approach of 14 patients with 5a-reductase deficiency in China.Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene(SRD5A2).The 5a-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay.Most patients presented with a microphallus,variable degrees of hypospadias,and cryptorchidism.Eight of 14 patients(57.1%)were initially reared as females and changed their social gender from female to male after puberty.Nine mutations were identified in the 14 patients.p.G203S,p.Q6X,and p.R227Q were the most prevalent mutations.Three mutations(p.K35N,p.H162P,and p.Y136X)have not been reported previously.The nonsense mutation p.Y136X abolished enzymatic activity,whereas p.K35N and p.H162P retained partial enzymatic activity.Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results.In conclusion,we expand the mutation profile of SRD5A2 in the Chinese population.A rational clinical approach to this disorder requires early and accurate diagnosis,especially genetic diagnosis.展开更多
基金This study is supported by grants from the National Natural Science Foundation(No.81570753,81430019 and 81873652)the Shanghai Jiao Tong University Medical and Engineering Intersection Foundation(No.YG2015QN03).
文摘In this study,we investigated the genetics,clinical features,and therapeutic approach of 14 patients with 5a-reductase deficiency in China.Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene(SRD5A2).The 5a-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay.Most patients presented with a microphallus,variable degrees of hypospadias,and cryptorchidism.Eight of 14 patients(57.1%)were initially reared as females and changed their social gender from female to male after puberty.Nine mutations were identified in the 14 patients.p.G203S,p.Q6X,and p.R227Q were the most prevalent mutations.Three mutations(p.K35N,p.H162P,and p.Y136X)have not been reported previously.The nonsense mutation p.Y136X abolished enzymatic activity,whereas p.K35N and p.H162P retained partial enzymatic activity.Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results.In conclusion,we expand the mutation profile of SRD5A2 in the Chinese population.A rational clinical approach to this disorder requires early and accurate diagnosis,especially genetic diagnosis.
