Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency
Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency
复制标题
中国 5α-还原酶 2 缺乏症患者中三种新的 SRD5A2 突变的鉴定
DOI：
10.4103/aja.aja_113_18
复制
发表时间：
2019-11-01
影响因子：
2.9
通讯作者：
Qiao, Jie
中科院分区：
文献类型：
--
作者：
Cheng, Tong;Wang, Hao;Qiao, Jie
在这项研究中，我们调查了中国14例5 α-还原酶缺乏症患者的遗传学、临床特征和治疗方法。通过类固醇5 α-还原酶2型基因（SRD 5A 2）的PCR产物直接测序进行基因分型分析。通过诱变和体外转染试验研究了三种新突变的5 α-还原酶活性。大多数患者表现为小阴茎、不同程度的尿道下裂和隐睾。14例患者中有8例（57.1%）最初被作为女性抚养，青春期后社会性别由女性变为男性。在14名患者中发现了9种突变。p.G203S、p.Q6X和p.R227Q是最常见的突变。有三个突变（p.K35N、p.H162P和p.Y136X）以前没有报道过。无义突变p.Y136X消除了酶活性，而p.K35N和p.H162P保留了部分酶活性。在婴儿期或儿童早期局部应用双氢睾酮联合尿道下裂修复术具有良好的治疗效果。总之，我们扩大了SRD 5A 2在中国人群中的突变谱。合理的临床治疗方法需要早期和准确的诊断，特别是遗传学诊断。
In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5 alpha-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5 alpha-reductase type 2 gene (SRD5A2). The 5 alpha-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.