Silver R I, Russell D W
Department of Surgery, Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA.
J Urol. 1999 Sep;162(3 Pt 2):1142-5. doi: 10.1016/S0022-5347(01)68102-3.
We determined whether 5a-reductase type 2 mutations are present in boys with isolated hypospadias.
Penile skin tissues obtained at surgery during hypospadias repair were examined for 5alpha-reductase type 2 mutations by single strand conformational polymorphism and deoxyribonucleic acid sequence analysis. Clinical data, including family history of hypospadias and preoperative position of the urethral meatus, were correlated with the genetic findings.
Of the 81 specimens examined 7 (8.6%) involved a mutation in at least 1, 5alpha-reductase type 2 gene, while 2 patients had mutations in both alleles. The mutations identified were A49T, L113V and H231R. The A49T mutation in 5 patients was the most common (71%) and it was generally present in less severe forms of hypospadias. To our knowledge neither the A49T nor the L113V mutation has been previously reported in association with 5alpha-reductase type 2 deficiency and to date they have only been identified in cases of isolated hypospadias. Family history was negative in the 7 patients with 5a-reductase type 2 mutations but positive in 5 without mutations.
Some boys with isolated hypospadias have a mutation in at least 1 gene for 5alpha-reductase type 2. This finding suggests that a partial deficiency of 5alpha-reductase activity and inadequate levels of dihydrotestosterone in the fetal urethra may be sufficient to cause the phenotype of hypospadias without other clinical features of 5alpha-reductase deficiency. Family history may not be reliable for determining which boys with hypospadias are likely to have such mutations.
我们确定了孤立性尿道下裂男孩中是否存在2型5α-还原酶突变。
在尿道下裂修复手术中获取阴茎皮肤组织，通过单链构象多态性和脱氧核糖核酸序列分析检测2型5α-还原酶突变。将临床数据，包括尿道下裂家族史和术前尿道口位置，与基因检测结果进行关联分析。
在检测的81个样本中，7个（8.6%）至少有1个2型5α-还原酶基因突变，2例患者两个等位基因均发生突变。鉴定出的突变有A49T、L113V和H231R。5例患者中的A49T突变最为常见（71%），且通常存在于较轻类型的尿道下裂中。据我们所知，A49T和L113V突变此前均未被报道与2型5α-还原酶缺乏相关，迄今为止仅在孤立性尿道下裂病例中被发现。7例2型5α-还原酶基因突变患者的家族史为阴性，而5例无突变患者的家族史为阳性。
一些孤立性尿道下裂男孩至少有1个2型5α-还原酶基因突变。这一发现表明，胎儿尿道中5α-还原酶活性部分缺乏和双氢睾酮水平不足可能足以导致尿道下裂的表型，而无5α-还原酶缺乏的其他临床特征。家族史对于确定哪些尿道下裂男孩可能存在此类突变可能并不可靠。
