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
目的探讨类固醇5α-还原酶2型缺乏症(SRD5A2)的临床特点、基因突变特征。方法回顾分析1例以外阴异常为初诊表现的SRD5A2患儿的临床资料。结果患儿,2岁5个月,社会性别为女性。基础促黄体生成素(LH)0.07 m IU/mL、促卵泡激素(FSH)0.39 m I...目的探讨类固醇5α-还原酶2型缺乏症(SRD5A2)的临床特点、基因突变特征。方法回顾分析1例以外阴异常为初诊表现的SRD5A2患儿的临床资料。结果患儿,2岁5个月,社会性别为女性。基础促黄体生成素(LH)0.07 m IU/mL、促卵泡激素(FSH)0.39 m IU/mL;人绒毛膜促性腺激素(HCG)刺激试验前后,睾酮分别是0.06 ng/mL、3.65ng/mL,双氢睾酮(DHT)分别是19.67 pg/mL、68.25 pg/mL;17-羟孕酮(17-OHP)1.20 ng/mL,雄烯二酮(A 2)0.07 ng/mL;HCG试验后T/DHT为51.72、T/A 2为14.70;抗苗勒管激素(AMH)22.97 ng/mL,抑制素B(INH-B)274.4 pg/mL。盆腔超声和磁共振均未探及子宫及卵巢。染色体为46,XY;性别决定(SRY)基因检测无异常;雄激素受体(AR)基因结果阴性。患儿及父母外周血均检测到2型5α-还原酶(SRD5A2)基因的致病性突变。应用2.5%DHT凝胶涂抹阴茎4个月后阴茎增长2 cm。结论 SRD5A2的诊断以HCG试验后T/DHT增高为主要依据,检测到致病性的SRD5A2基因突变可确诊。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.
