Dohle G R, Halley D J J, Van Hemel J O, van den Ouwel A M W, Pieters M H E C, Weber R F A, Govaerts L C P
Andrology Unit, Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Hum Reprod. 2002 Jan;17(1):13-6. doi: 10.1093/humrep/17.1.13.
Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors.
In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome abnormalities, microdeletions of the Y chromosome (AZF region) and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Genetic analysis identified 16/150 (10.6%) abnormal karyotypes, 8/150 (5.3%) AZFc deletions and 14/150 (9.3%) CFTR gene mutations. An abnormal karyotype was found both in men with oligozoospermia and azoospermia: 9 men had a sex-chromosomal aneuploidy, 6 translocations were identified and one marker chromosome was found. Y chromosomal microdeletions were mainly associated with male infertility, due to testicular insufficiency. All deletions identified comprised the AZFc region, containing the Deleted in Azoospermia (DAZ) gene. CFTR gene mutations were commonly seen in men with congenital absence of the vas deferens, but also in 16% of men with azoospermia without any apparent abnormality of the vas deferens.
A genetic abnormality was identified in 36/150 (24%) men with extreme oligozoospermia and azoospermia. Application of ICSI in these couples can result in offspring with an enhanced risk of unbalanced chromosome complement, male infertility due to the transmission of a Y-chromosomal microdeletion, and cystic fibrosis if both partners are CFTR gene mutation carriers. Genetic testing and counselling is clearly indicated for these couples before ICSI is considered.
严重少精子症和无精子症导致的男性不育与多种遗传风险因素有关。
在本研究中，对150名来自要求进行卵胞浆内单精子注射（ICSI）的夫妇的男性进行了遗传异常调查，如染色体结构异常、Y染色体微缺失（无精子症因子区域）以及囊性纤维化跨膜传导调节因子（CFTR）基因突变。
遗传分析发现16/150（10.6%）的核型异常、8/150（5.3%）的AZFc缺失以及14/150（9.3%）的CFTR基因突变。少精子症和无精子症男性均发现有核型异常：9名男性存在性染色体非整倍体，鉴定出6种易位，发现1条标记染色体。Y染色体微缺失主要与睾丸功能不全导致的男性不育有关。所有鉴定出的缺失均包含AZFc区域，该区域含有无精子症缺失（DAZ）基因。CFTR基因突变常见于先天性输精管缺如的男性，但在16%无明显输精管异常的无精子症男性中也有发现。
在150名严重少精子症和无精子症男性中，有36/150（24%）发现了遗传异常。对这些夫妇应用ICSI可能导致后代出现染色体组不平衡风险增加、因Y染色体微缺失遗传而导致男性不育以及如果父母双方均为CFTR基因突变携带者则会出现囊性纤维化的情况。在考虑进行ICSI之前，显然应对这些夫妇进行基因检测和遗传咨询。
