Department of Andrology, The Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Clin Genet. 2023 Nov;104(5):577-581. doi: 10.1111/cge.14392. Epub 2023 Jun 19.
Genetic causation for the majority of non-obstructive azoospermia (NOA) remains unclear. Mutations in synaptonemal complex (SC)-associated genes could cause meiotic arrest and NOA. Previous studies showed that heterozygous truncating variants in SYCP2 encoding a protein essential for SC formation, are associated with non-obstructive azoospermia and severe oligozoospermia. Herein, we showed a homozygous loss-of-function variant in SYCP2 (c.2689_2690insT) in an NOA-affected patient. And this variant was inherited from heterozygous parental carriers by natural reproduction. HE, IF, and meiotic chromosomal spread analyses demonstrated that spermatogenesis was arrested at the zygotene stage in the proband with NOA. Thus, this study revealed that SYCP2 associated with NOA segregates in an autosomal recessive inheritance pattern, rather than an autosomal dominant pattern. Furthermore, our study expanded the knowledge of variants in SYCP2 and provided new insight into understanding the genetic etiology of NOA.
大多数非阻塞性无精子症（NOA）的遗传原因尚不清楚。联会复合体（SC）相关基因的突变可导致减数分裂阻滞和 NOA。先前的研究表明，编码 SC 形成所必需的蛋白质的 SYCP2 中的杂合截断变体与非阻塞性无精子症和严重少精子症有关。在此，我们在一名 NOA 患者中显示出 SYCP2 中的纯合功能丧失变异（c.2689_2690insT）。并且该变体是通过自然繁殖从杂合父母携带者遗传而来的。HE、IF 和减数分裂染色体铺展分析表明，该 NOA 先证者的精子发生在合线期被阻滞。因此，这项研究表明，与 NOA 相关的 SYCP2 以常染色体隐性遗传模式遗传，而不是常染色体显性遗传模式。此外，我们的研究扩展了 SYCP2 中变异的知识，并为理解 NOA 的遗传病因提供了新的见解。
