Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
Kaohsiung J Med Sci. 2012 Apr;28(4):231-5. doi: 10.1016/j.kjms.2011.10.011. Epub 2012 Feb 18.
The 5α-reductase type 2 deficiency is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5α-reductase type 2 (SRD5A2) gene. In this disease, defective conversion of testosterone to dihydrotestosterone leads to variable presentations of male ambiguous genitalia during fetal development. The most crucial clinical decision for the affected individual is proper gender assignment; therefore, a prompt and correct diagnosis is important. In this present study, we report a normal male karyotype manifesting microphallus, bifid scrotum/labia majora with bilateral palpable gonads, and a blind-ended pseudovagina. The mutation analysis of the SRD5A2 gene revealed one novel C to T transition changing glutamine to a stop codon at codon 71 (p.Q71X) in exon 1 and one known G to A transition changing arginine to glutamine at codon 227 (p.R227Q) in exon 4. The p.Q71X mutation presumably results in a truncated protein, while the p.R227Q mutation is conceived to impair enzyme function and has been reported in patients of East Asian descent. This report demonstrates the essential role of hormonal and molecular studies for genetic counseling and gender assignment in males with pseudovaginal disorder of sex development, and our report helps identify a novel SRD5A2 gene mutation in the Taiwanese population.
5α-还原酶 2 型缺乏症是一种罕见的常染色体隐性 46,XY 性发育障碍，由突变的 5α-还原酶 2 型（SRD5A2）基因引起。在这种疾病中，睾酮向二氢睾酮的转化缺陷导致胎儿发育过程中男性生殖器出现不同程度的模糊表现。对于受影响的个体来说，最重要的临床决策是正确的性别分配；因此，及时准确的诊断很重要。在本研究中，我们报告了一个正常男性核型表现为小阴茎、分叉阴囊/大阴唇伴双侧可触及的性腺和盲端假阴道。SRD5A2 基因突变分析显示，第 1 外显子中 71 号密码子的 C 到 T 颠换导致谷氨酰胺突变为终止密码子（p.Q71X），第 4 外显子中 227 号密码子的 G 到 A 颠换导致精氨酸突变为谷氨酰胺（p.R227Q）。p.Q71X 突变可能导致截短蛋白，而 p.R227Q 突变被认为会损害酶的功能，并已在东亚裔患者中报道过。本报告证明了激素和分子研究在有假阴道性发育障碍的男性进行遗传咨询和性别分配中的重要作用，我们的报告有助于确定台湾人群中存在新的 SRD5A2 基因突变。
