MUTATIONS IN THE CYSTIC-FIBROSIS GENE IN PATIENTS WITH CONGENITAL ABSENCE OF THE VAS-DEFERENS
MUTATIONS IN THE CYSTIC-FIBROSIS GENE IN PATIENTS WITH CONGENITAL ABSENCE OF THE VAS-DEFERENS
复制标题
DOI：
10.1056/nejm199506013322204
复制
发表时间：
1995-06-01
影响因子：
158.5
通讯作者：
ESTIVILL, X
中科院分区：
文献类型：
--
作者：
CHILLON, M;CASALS, T;ESTIVILL, X
背景先天性双侧输精管缺如（CBAVD）是男性不育的一种形式，其中囊性纤维化跨膜传导调节因子（CFTR）基因突变已被确定。CBAVD的分子基础尚未完全了解。虽然囊性纤维化患者的CFTR基因的两个拷贝都有突变，但大多数CBAVD患者的基因只有一个拷贝突变。为了在分子水平上研究CBAVD，我们对102例CBAVD患者的CFTR基因突变进行了表征。无囊性纤维化的临床表现。我们还分析了CFTR非编码区的DNA变体（5T等位基因），该变体导致正常CFTR蛋白水平降低。以囊性纤维化患者的父母、CBAVD以外的不孕症患者和正常人作为对照。102名CBAVD患者中有19名CFTR基因的两个拷贝都有突变，没有一个有5T等位基因。54名患者在CFTR的一个拷贝中有突变，其中34人（63%）在另一个CFTR基因中有5T等位基因。在29名患者中没有发现CFTR突变，但其中7人（24%）有5T等位基因。相反，该等位基因在一般人群中的频率约为50%。大多数CBAVD患者CFTR基因突变。CFTR基因的一个拷贝中的5T等位基因与另一个拷贝中的囊性纤维化突变的组合是CBAVD的最常见原因。5T等位基因突变具有广泛的临床表现，发生在CBAVD或中度囊性纤维化患者和生育男性中。
Background. Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. The molecular basis of CBAVD is not completely understood. Although patients with cystic fibrosis have mutations in both copies of the CFTR gene, most patients with CBAVD have mutations in only one copy of the gene.Methods. To investigate CBAVD at the molecular level, we have characterized the mutations in the CFTR gene in 102 patients with this condition. None had clinical manifestations of cystic fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of CFTR that causes reduced levels of the normal CFTR protein. Parents of patients with cystic fibrosis, patients with types of infertility other than CBAVD, and normal subjects were studied as controls.Results. Nineteen of the 102 patients with CBAVD had mutations in both copies of the CFTR gene, and none of them had the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In contrast, the frequency of this allele in the general population was about 5 percent.Conclusions. Most patients with CBAVD have mutations in the CFTR gene. The combination of the 5T allele in one copy of the CFTR gene with a cystic fibrosis mutation in the other copy is the most common cause of CBAVD. The 5T allele mutation has a wide range of clinical presentations, occurring in patients with CBAVD or moderate forms of cystic fibrosis and in fertile men.