Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China.
Clin Genet. 2023 Oct;104(4):486-490. doi: 10.1111/cge.14380. Epub 2023 Jun 4.
Premature ovarian insufficiency (POI) is a heterogeneous disease affecting the physical and mental health of millions of women worldwide. The contribution of genetic factors in the pathogenesis of POI has increased, with quite a few of causative genes involved in meiosis. ZMM proteins are a group of conserved proteins participating in meiotic synapsis and crossover maturation. Here, by screening the variations of ZMM genes in our in-house WES database of 1030 idiopathic POI patients, one novel homozygous variation in SPO16 (c.160 + 8A > G) was firstly identified in one patient. The variation was verified to disturb mRNA splicing by minigene assay, produced a non-functional SPO16 protein, and was classified as pathogenetic according to American College of Medical Genetics guideline. During meiotic prophase I, SHOC1 binds to branched DNA and recruits SPO16 and other ZMM proteins to facilitate crossover formation. Together with our recent identified bi-allelic variations of SHOC1 in a published work, this study highlighted the essential roles of ZMM genes in the maintenance of ovarian function and expanded the POI gene spectrum.
卵巢早衰（POI）是一种影响全球数百万妇女身心健康的异质性疾病。遗传因素在 POI 的发病机制中的作用增加了，相当多的致病基因参与了减数分裂。ZMM 蛋白是一组参与减数分裂联会和交叉成熟的保守蛋白。在这里，通过筛选我们在 1030 例特发性 POI 患者的内部 WES 数据库中的 ZMM 基因变异，在一名患者中首次发现了 SPO16 中的一个新的纯合变异（c.160+8A>G）。通过微基因检测证实该变异干扰了 mRNA 的剪接，产生了无功能的 SPO16 蛋白，并根据美国医学遗传学学院的指南将其分类为致病性变异。在减数分裂前期 I 中，SHOC1 与分支 DNA 结合，并募集 SPO16 和其他 ZMM 蛋白以促进交叉形成。结合我们最近在已发表的研究中发现的 SHOC1 的双等位基因变异，本研究强调了 ZMM 基因在维持卵巢功能中的重要作用，并扩展了 POI 的基因谱。
