Mercier B, Verlingue C, Lissens W, Silber S J, Novelli G, Bonduelle M, Audrézet M P, Férec C
Centre de Biogénétique C.D.T.S., Brest, France.
Am J Hum Genet. 1995 Jan;56(1):272-7.
Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of sterility in men. Although the genetic basis of this condition is still unclear, it has been shown recently that some of these patients carry mutations in their cystic fibrosis transmembrane conductance regulator (CFTR) genes. To extend this observation, we have analyzed the entire coding sequence of the CFTR gene in a cohort of 67 men with CBAVD, who are otherwise healthy. We have identified four novel missense mutations (A800G, G149R, R258G, and E193K). We have shown that 42% of subjects were carriers of one CFTR allele and that 24% are compound heterozygous for CFTR alleles. Thus, we have been unable to identify 76% of these patients as carrying two CFTR mutations. Furthermore, we have described the segregation of CFTR haplotypes in the family of one CBAVD male; in this family are two male siblings, with identical CFTR loci but displaying different phenotypes, one of them being fertile and the other sterile. The data presented in this family, indicating a discordance between the CBAVD phenotype and a marked carrier (delta F508) chromosome, support the involvement of another gene(s), in the etiology of CBAVD.
先天性双侧输精管缺如（CBAVD）是男性不育的一个重要原因。尽管这种病症的遗传基础仍不清楚，但最近有研究表明，部分此类患者的囊性纤维化跨膜传导调节因子（CFTR）基因存在突变。为拓展这一观察结果，我们分析了67名患有CBAVD且无其他健康问题的男性群体中CFTR基因的完整编码序列。我们鉴定出四个新的错义突变（A800G、G149R、R258G和E193K）。我们发现，42%的受试者为一个CFTR等位基因的携带者，24%为CFTR等位基因的复合杂合子。因此，我们无法确定76%的这些患者携带两个CFTR突变。此外，我们描述了一名CBAVD男性患者家族中CFTR单倍型的分离情况；在这个家族中有两个男性同胞，他们具有相同的CFTR基因座，但表现出不同的表型，其中一个可育，另一个不育。该家族呈现的数据表明，CBAVD表型与一个显著的携带者（ΔF508）染色体之间存在不一致，这支持了另一个基因参与CBAVD病因的观点。
