MAGI EUREGIO, Bolzano, Italy.
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Front Endocrinol (Lausanne). 2021 Jan 26;11:605237. doi: 10.3389/fendo.2020.605237. eCollection 2020.
Infertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of "diagnostic" genes, for a wide panel of genes that we have defined as "pre-diagnostic."
We developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes.
After NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of and genes and three uncertain significance variants of , , and genes were found. Moreover, three variants with high impact were found in , , and genes.
This study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism.
不孕不育影响约 7%的普通男性人群。约 50%的病例（特发性不育）的男性不育根本原因尚不清楚。涉及人类精子发生的基因数量超过两千个。因此，分析可能涉及男性不育的大量基因至关重要。本研究旨在测试经“诊断性”基因验证性面板检测为阴性的特发性男性不育患者，这些患者是否存在我们定义为“预诊断性”的广泛基因。
我们开发了一种下一代测序（NGS）基因面板，包括 65 个预诊断性基因，这些基因用于 12 名经男性不育症疾病诊断性遗传检测呈阴性的患者，这些患者包括原发性生精失败和中枢性性腺功能减退症，共包含 110 个基因。
在进行 NGS 测序后，在 12 名经原发性生精失败（n = 9）或中枢性性腺功能减退症（n = 1）诊断性检测呈阴性的患者中，发现了 10 名患者的预诊断性基因中有突变。这些患者的单一基因发生突变，导致原发性生精失败或中枢性性腺功能减退症。发现了 和 基因的两个致病性变异，以及 、 和 基因的三个不确定意义的变异。此外，在 、 和 基因中还发现了三个具有高影响的变异。
本研究表明，在具有明显特发性原发性生精失败和中枢性性腺功能减退症的患者中，寻找预诊断性基因可能有助于找到不育的原因，这些患者的病因是单一基因突变。
