Ishii T, Sato S, Kosaki K, Sasaki G, Muroya K, Ogata T, Matsuo N
Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan.
J Clin Endocrinol Metab. 2001 Nov;86(11):5372-8. doi: 10.1210/jcem.86.11.7999.
Various mutations of the AR gene and expanded CAG repeats at exon 1 of that gene have been reported in patients with hypospadias or genital ambiguity. However, the role of the AR gene has not been systemically studied in those with isolated micropenis lacking hypospadias or genital ambiguity. We studied 64 Japanese boys with isolated micropenis (age, 0-14 yr; median, 7 yr), whose stretched penile lengths were between -2.5 and -2.0 SD (borderline micropenis) in 31 patients (age, 0-13 yr; median, 8 yr) and below -2.5 SD (definite micropenis) in 33 patients (age, 0-14 yr; median, 6 yr). Mutation analysis of the AR gene was performed for exons 1-8 and their flanking introns, except for the CAG and GGC repeat regions at exon 1, by denaturing HPLC and direct sequencing, identifying a substitution of cytosine to thymine at a position -3 in the 3' splice site of intron 1 in a patient with definite micropenis. CAG repeat length at exon 1 was determined by electrophoresis with internal size markers and direct sequencing, revealing no statistically significant difference in the distribution of CAG repeat lengths [median (range) and mean +/- SE: total patients with isolated micropenis, 24 (14-34) and 23.5 +/- 0.38; patients with borderline micropenis, 24 (15-29) and 23.5 +/- 0.53; patients with definite micropenis, 23 (14-34) and 23.5 +/- 0.56; and 100 control males, 23 (16-32) and 23.5 +/- 0.29] or in the frequency of long CAG repeats (percentage of CAG repeats > or =26 and > or =28: total patients with isolated micropenis, 17.2 and 4.7%; patients with borderline micropenis, 19.4 and 6.5%; patients with definite micropenis, 15.2 and 3.0%; and 100 control males, 21.0 and 10.0%). These results suggest that an AR gene mutation is rare and that CAG repeat length is not expanded in children with isolated micropenis.
尿道下裂或生殖器模糊患者中已报道了雄激素受体（AR）基因的各种突变以及该基因第1外显子中CAG重复序列的扩增。然而，AR基因在单纯性小阴茎（无尿道下裂或生殖器模糊）患者中的作用尚未得到系统研究。我们研究了64名日本单纯性小阴茎男孩（年龄0 - 14岁；中位数7岁），其中31名患者（年龄0 - 13岁；中位数8岁）阴茎拉伸长度在-2.5至-2.0标准差之间（临界小阴茎），33名患者（年龄0 - 14岁；中位数6岁）阴茎拉伸长度低于-2.5标准差（明确小阴茎）。除第1外显子的CAG和GGC重复区域外，对AR基因的第1 - 8外显子及其侧翼内含子进行了突变分析，采用变性高效液相色谱法和直接测序法，在1名明确小阴茎患者的第1内含子3'剪接位点-3位置发现胞嘧啶替换为胸腺嘧啶。通过电泳结合内部大小标记物和直接测序法测定第1外显子的CAG重复长度，结果显示CAG重复长度的分布[中位数（范围）和均值±标准误：单纯性小阴茎患者总数，24（14 - 34）和23.5±0.38；临界小阴茎患者，24（15 - 29）和23.5±0.53；明确小阴茎患者，23（14 - 34）和23.5±0.56；100名对照男性，23（16 - 32）和23.5±0.29]或长CAG重复序列的频率（CAG重复序列≥26和≥28的百分比：单纯性小阴茎患者总数为17.2%和4.7%；临界小阴茎患者为19.4%和6.5%；明确小阴茎患者为15.2%和3.0%；100名对照男性为21.0%和10.0%）均无统计学显著差异。这些结果表明，AR基因突变在单纯性小阴茎儿童中罕见，且CAG重复长度未扩增。
