Open AccessIdentification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency
Author(s) -
Tao Cheng,
Hao Wang,
Bing Han,
Hui Zhu,
Haijun Yao,
ShuangXia Zhao,
Weijun Zhu,
Hualing Zhai,
Fu-Guo Chen,
Hwangjun Song,
Kaixiang Cheng,
Yang Liu,
Jie Qiao
Publication year - 2019
Publication title -
asian journal of andrology/asian journal of andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 74
eISSN - 1745-7262
pISSN - 1008-682X
DOI - 10.4103/aja.aja_113_18
Subject(s) - nonsense mutation , mutation , genetics , reductase , genotyping , biology , hypospadias , medicine , gene , endocrinology , genotype , enzyme , missense mutation , biochemistry
In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-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.