Hussain Shah, Nawaz Shoaib, Khan Ihsan, Khan Nida, Hussain Shabir, Ullah Imran, Fakhro Khalid A, Ahmad Wasim
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan; Department of Human Genetics, Sidra Medicine, Doha, Qatar.
Eur J Med Genet. 2022 Nov;65(11):104629. doi: 10.1016/j.ejmg.2022.104629. Epub 2022 Oct 4.
Infertility is a common, clinically heterogeneous reproductive disorder worldwide with a prevalence of about 15%. To date about eighty genes have been discovered to cause non-syndromic infertility, affecting males and females equally, though traditionally the genetic analysis of each group has been conducted separately. Here, we report the clinical and genetic characterization of a consanguineous family of Pakistani origin with multiple individuals, including male and female, affected with infertility. Males exhibited non-obstructive azoospermia whereas females had primary ovarian insufficiency. Whole exome sequencing revealed a missense variant [c.176C > T, p. (Ser59Leu)] in the ZSWIM7 gene which functions in homologous recombination repair. The variant was found in a homozygous form in all affected males and females. To our knowledge, this is the first family that has individuals affected with infertility in both sexes. This point to the utility of large consanguineous families with multiple affected siblings to reveal joint mechanisms affecting human reproduction.
不孕症是一种常见的、临床异质性的生殖障碍，在全球范围内的患病率约为15%。迄今为止，已发现约80个基因可导致非综合征性不孕症，对男性和女性的影响相同，不过传统上对每组的基因分析是分开进行的。在此，我们报告了一个来自巴基斯坦的近亲家庭的临床和基因特征，该家庭中有多名个体（包括男性和女性）患有不孕症。男性表现为非梗阻性无精子症，而女性则患有原发性卵巢功能不全。全外显子组测序揭示了ZSWIM7基因中的一个错义变异[c.176C>T，p.(Ser59Leu)]，该基因在同源重组修复中发挥作用。该变异在所有受影响的男性和女性中均以纯合形式存在。据我们所知，这是第一个有男女两性都受不孕症影响个体的家庭。这表明具有多个患病兄弟姐妹的大型近亲家庭在揭示影响人类生殖的联合机制方面具有实用性。
