Identification of a missense variant of MND1 in meiotic arrest and non-obstructive azoospermia
Identification of a missense variant of MND1 in meiotic arrest and non-obstructive azoospermia
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DOI：
10.1038/s10038-023-01172-y
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发表时间：
2023-06-26
影响因子：
3.5
通讯作者：
Li，Peng
中科院分区：
文献类型：
--
作者：
Zhao，Jingpeng;Ji，Zhiyong;Li，Peng
减数分裂停滞是非阻塞性无精子症（NOA）常见的病理表型，但其遗传原因还需要进一步研究。减数分裂核分裂1（MND 1）已被证明是许多物种减数分裂重组所不可或缺的。迄今为止，只有一种MND 1变异与原发性卵巢功能不全（POI）相关，但还没有与NOA相关的MND 1变异的报道。在此，我们在来自一个中国家庭的两名NOA感染患者中鉴定了MND 1的一种罕见的纯合错义变体（NM_032117：c.G507C：p.W169C）。组织学分析和免疫组化显示，减数分裂阻滞在合子样阶段的前期I和缺乏精子的先证者的曲细精管。计算机模拟表明，该变体可能导致MND 1-HOP 2复合物的具有加帽螺旋的亮氨酸拉链3（LZ 3 wCH）结构域的可能构象变化。总之，我们的研究表明，MND 1变异体（c.G507C）可能是负责人类减数分裂阻滞和NOA。我们的研究为NOA的遗传病因学和雄性减数分裂中同源重组修复机制提供了新的见解。
Meiotic arrest is a common pathologic phenotype of non-obstructive azoospermia (NOA), yet its genetic causes require further investigation.Meiotic nuclear divisions 1(MND1)has been proved to be indispensable for meiotic recombination in many species. To date, only one variant ofMND1has been reported associated with primary ovarian insufficiency (POI), yet there has been no report of variants inMND1associated with NOA. Herein, we identified a rare homozygous missense variant (NM_032117:c.G507C:p.W169C) ofMND1in two NOA-affected patients from one Chinese family. Histological analysis and immunohistochemistry demonstrated meiotic arrest at zygotene-like stage in prophase I and lack of spermatozoa in the proband’s seminiferous tubules. In silico modeling demonstrated that this variant might cause possible conformational change in the leucine zippers 3 with capping helices (LZ3wCH) domain of MND1-HOP2 complex. Altogether, our study demonstrated that theMND1variant (c.G507C) is likely responsible for human meiotic arrest and NOA. And our study provides new insights into the genetic etiology of NOA and mechanisms of homologous recombination repair in male meiosis.