Cannarella Rossella, Precone Vincenza, Guerri Giulia, Busetto Gian Maria, Di Renzo Gian Carlo, Gerli Sandro, Manara Elena, Dautaj Astrit, Bertelli Matteo, Calogero Aldo Eugenio
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
MAGI EUREGIO, 39100 Bolzano, Italy.
Life (Basel). 2020 Oct 15;10(10):242. doi: 10.3390/life10100242.
Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants.
We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia.
NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in , , , and genes. Moreover, 14 variants of unknown significance and 7 novel variants were found that require further functional studies and family segregation.
This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility.
高达15%的夫妇存在不孕问题，其中男性因素导致的不孕约占这些病例的50%。男性不育是一种多因素病理状况。男性不育的遗传学非常复杂，其病因至少涉及2000个基因。通过下一代测序（NGS）技术进行基因检测对男性不育患者具有诊断价值。因此，本研究的目的是利用NGS基因 panel来识别基因变异，从而提供诊断方法。
我们开发了一种NGS基因panel，并将其应用于22例男性不育患者。该panel由110个基因组成，用于探究男性不育的遗传原因，即单基因突变导致的精子发生失败、中枢性性腺功能减退、雄激素不敏感综合征、先天性垂体功能减退和原发性纤毛运动障碍。
通过NGS以及对阳性致病或可能致病变异的后续测序，发现5例患者（23%）存在分子缺陷。具体而言，在 、 、 和 基因中鉴定出了致病变异。此外，还发现了14个意义未明的变异和7个新变异，需要进一步的功能研究和家系分离分析。
这种基于NGS的扩展诊断方法可能是诊断男性不育的有用工具。通过NGS开发定制的基因panel似乎能够降低男性特发性不育的比例。
