Kanavakis E, Tzetis M, Antoniadi T, Pistofidis G, Milligos S, Kattamis C
First Department of Pediatrics, Athens University, St Sophia's Children's Hospital, Greece.
Mol Hum Reprod. 1998 Apr;4(4):333-7. doi: 10.1093/molehr/4.4.333.
Congenital bilateral absence of the vas deferens (CBAVD) found in otherwise healthy infertile males, is associated with a high incidence of mutated cystic fibrosis transmembrane conductance regulator (CFTR) alleles, and is considered a genital form of cystic fibrosis (CF). The CF gene may also be involved in the aetiology of male infertility in cases other than CBAVD. The present study was undertaken to test the involvement of CFTR gene mutations in 14 CBAVD males and additionally in cases of male infertility caused by obstructive azoospermia (n = 10) and severe oligozoospermia (n = 3). The entire coding region of the CFTR gene was analysed using denaturing gradient gel electrophoresis (DGGE). The three allele (5T, 7T, 9T) polymorphic tract of thymidines in intron 8 (IVS8-polyT) of which the 5T allele acts as a mild mutation, causing reduced levels of normal CFTR mRNA due to deletion of exon 9, was also analysed. Of the 14 CBAVD cases, four (28.6%) were found to have mutations in both copies of the CFTR gene, six (42.8%) had one CFTR mutation, and in the remaining four (28.6%) no CFTR mutations were found. Of the 10 cases with obstructive azoospermia, three (30%) had one CFTR mutation and in the remaining seven (70%) no mutations were found. None of the three severe oligozoospermia cases carried a CFTR mutation. The frequency of the IVS8(5T) allele was 14.3% (4/28) for the CBAVD cases and 5% (1/20) for the obstructive azoospermia cases, none of the severe oligozoospermia males carried the IVS8-5(5T) allele. The data indicate that while there is a strong association between male infertility caused by CBAVD and mutations in the CFTR gene, cases of obstructive azoospermia without CBAVD also seem to be associated with CFTR gene mutations.
先天性双侧输精管缺如（CBAVD）见于其他方面健康的不育男性，与囊性纤维化跨膜传导调节因子（CFTR）等位基因突变的高发生率相关，被认为是囊性纤维化（CF）的一种生殖器形式。CF基因也可能参与除CBAVD之外的其他男性不育病因。本研究旨在检测14例CBAVD男性以及另外由梗阻性无精子症（n = 10）和严重少精子症（n = 3）导致的男性不育病例中CFTR基因突变的情况。使用变性梯度凝胶电泳（DGGE）分析CFTR基因的整个编码区。还分析了第8内含子（IVS8 - polyT）中三个等位基因（5T、7T、9T）的胸腺嘧啶多态性区域，其中5T等位基因作为一种轻度突变，由于外显子9缺失导致正常CFTR mRNA水平降低。在14例CBAVD病例中，4例（28.6%）被发现CFTR基因的两个拷贝均有突变，6例（42.8%）有一个CFTR突变，其余4例（28.6%）未发现CFTR突变。在10例梗阻性无精子症病例中，3例（30%）有一个CFTR突变，其余7例（70%）未发现突变。3例严重少精子症病例均未携带CFTR突变。CBAVD病例中IVS8(5T)等位基因的频率为14.3%（4/28），梗阻性无精子症病例为5%（1/20），严重少精子症男性均未携带IVS8 - 5(5T)等位基因。数据表明，虽然CBAVD导致的男性不育与CFTR基因突变之间存在很强的关联，但无CBAVD的梗阻性无精子症病例似乎也与CFTR基因突变有关。
