Nuti Francesca, Krausz Csilla
Andrology Unit, Department of Clinical Physiopathology, Viale Pieraccini, 6, 50139 Florence, Italy.
Reprod Biomed Online. 2008 Apr;16(4):504-13. doi: 10.1016/s1472-6483(10)60457-9.
Despite the identification of an increasing number of candidate genes involved in spermatogenesis, the armamentarium of diagnostic genetic tests in male infertility remains extremely limited. A number of new causative mutations have been reported for hypogonadotrophic hypogonadism but still the genetic diagnosis in this pathological condition is made only in about 20% of cases. The sole molecular genetic test that is routinely proposed in severe spermatogenic disturbances is screening for Yq microdeletion. The search for causative mutations in the Y chromosome, and in autosomal and X-linked genes, has mostly been unsuccessful. The paucity of gene mutations raises questions about the appropriateness of the currently used screening approaches. Among the proposed genetic risk factors, gr/gr deletion of the Y chromosome seems to be the most promising polymorphism. Other polymorphisms are awaiting further confirmation, whereas for some (POLG, DAZL, USP26, FSHR) a lack of association with abnormal spermatogenesis has now been ascertained. It is likely that some polymorphisms lead to testicular dysfunction only when in association with a specific genetic background or with environmental factors. Future large-scale studies with stringent study design may provide a more efficient way to identify clinically relevant genetic factors of male infertility.
尽管已鉴定出越来越多与精子发生相关的候选基因,但男性不育诊断性基因检测手段仍然极为有限。对于低促性腺激素性性腺功能减退,已报道了许多新的致病突变,但在这种病理状况下,基因诊断仅在约20%的病例中得以进行。在严重生精障碍中常规开展的唯一分子遗传学检测是Yq微缺失筛查。在Y染色体以及常染色体和X连锁基因中寻找致病突变大多未成功。基因突变的稀少引发了对当前所用筛查方法适当性的质疑。在已提出的遗传风险因素中,Y染色体的gr/gr缺失似乎是最有前景的多态性。其他多态性尚待进一步证实,而对于某些基因(POLG、DAZL、USP26、FSHR),现已确定它们与异常精子发生无关。某些多态性可能仅在与特定遗传背景或环境因素相关联时才会导致睾丸功能障碍。未来采用严格研究设计的大规模研究可能会提供一种更有效的方法来识别男性不育的临床相关遗传因素。