Bahceci Mithat, Ersay Ahmet Resit, Tuzcu Alpaslan, Hiort Olaf, Richter-Unruh Annette, Gokalp Deniz
Department of Endocrinology, University of Dicle, School of Medicine, Diyarbakir, Turkey.
Urology. 2005 Aug;66(2):407-10. doi: 10.1016/j.urology.2005.02.021.
To analyze the steroid 5-alpha reductase type 2 gene (SRD5A2) in 2 siblings with severe male pseudohermaphroditism suspected to have 5-alpha reductase deficiency in a Turkish family.
Two female siblings of a family with 7 children were referred to the urology department because of bilateral inguinal masses. The patients had presented after birth with ambiguous genitalia, but no further diagnostic procedures had been performed, and they were raised as girls until the ages of 13 and 15 years. At this time, both had striking ambiguity of the genitalia, with a clitoris-like phallus, severely bifid scrotum, pseudovaginal perineoscrotal hypospadias, a rudimentary prostate, and inguinal testes. Karyotype was 46,XY. Basal and stimulated levels of serum testosterone (T), dihydrotestosterone (DHT), and T/DHT ratio indicated 5-alpha reductase deficiency. Molecular genetic analysis was performed on deoxyribonucleic acid from peripheral blood leukocytes by single-stranded conformational polymorphism analysis and direct sequencing.
Analysis of the SRD5A2 gene revealed a new homozygous missense mutation in exon 2. At codon 123, we identified a GGA to AGA change resulting in a missense amino acid change from glycine to arginine (G123R). Both parents and the 2 healthy sisters and 3 brothers were all heterozygous at codon 123 for the same mutation.
We report a novel homozygous missense mutation in exon 2 of the 5-alpha reductase type 2 gene that led to severe undervirilization in 2 siblings.
对一个土耳其家庭中2名疑似患有5α-还原酶缺乏症的严重男性假两性畸形的同胞进行类固醇5α-还原酶2型基因（SRD5A2）分析。
一个有7个孩子的家庭中的2名女性同胞因双侧腹股沟肿块被转诊至泌尿外科。这两名患者出生时生殖器模糊，但未进行进一步的诊断程序，直到13岁和15岁一直被当作女孩抚养。此时，两人的生殖器均有明显的模糊特征，有类似阴蒂的阴茎、严重的阴囊分裂、会阴阴囊型假阴道尿道下裂、发育不全的前列腺和腹股沟睾丸。核型为46,XY。血清睾酮（T）、双氢睾酮（DHT）的基础水平和刺激水平以及T/DHT比值表明存在5α-还原酶缺乏。通过单链构象多态性分析和直接测序对来自外周血白细胞的脱氧核糖核酸进行分子遗传学分析。
SRD5A2基因分析显示外显子2中有一个新的纯合错义突变。在第123密码子处，我们鉴定出一个从GGA到AGA的变化，导致从甘氨酸到精氨酸的错义氨基酸变化（G123R）。父母以及2名健康的姐妹和3名兄弟在第123密码子处均为该相同突变的杂合子。
我们报告了5α-还原酶2型基因外显子2中的一种新的纯合错义突变，该突变导致2名同胞出现严重的男性化不足。
