由于透明带形成异常,ZP1、ZP2和ZP3的新突变导致女性不育。

PubMed ID
发表日期 2019年Apr月

原始出处 人类遗传学
Human genetics
作者 Zhou  Zhou  Ni  Caixia  Wu  Ling  Chen  Biaobang  Xu  Yao  Zhang  Zhihua  Mu  Jian  Li  Bin  Yan  Zheng  Fu  Jing  Wang  Wenjing  Zhao  Lin  Dong  Jie  Sun  Xiaoxi  Kuang  Yanping  Sang  Qing  Wang  Lei 

文献标题 由于透明带形成异常,ZP1、ZP2和ZP3的新突变导致女性不育。
Novel mutations in ZP1, ZP2, and ZP3 cause female infertility due to abnormal zona pellucida formation.

文献摘要

人卵透明带(ZP)是卵母细胞周围由ZP1、ZP2、ZP3和ZP4组成的细胞外糖蛋白基质,在受精过程中的精卵相互作用中起着重要作用。ZP的结构和功能改变会影响受精过程并导致女性不育。先前的研究已经确定ZP1、ZP2和ZP3的突变导致女性不育,这些不育由卵母细胞变性、空卵泡综合征或体外受精失败引起。在这里,我们描述了来自六个独立家庭的七名患者,他们有几个异常卵母细胞或患有空卵泡综合征,与之前报道的表型相似。通过全外显子组测序和Sanger测序,我们在这些患者中发现了一些新的突变。其中包括ZP1的三个纯合突变(c.1708G > A、 p.Val570Met;c、 1228C > T、 p.Arg410Trp;c、 507del,p.His170Ilefs*52),ZP1中复合杂合子状态的两个突变(c.1430 + 1克 > T、 p.Cys478X和c.1775-8T > C、 p.Asp592Glyfs*29),ZP2的纯合突变(C.1115G > C、 Cys372Ser)和ZP3的杂合突变(C.763C > G、 第Arg255Gly页)。此外,对CHO细胞的研究表明,ZP1、ZP2和ZP3的突变可能会影响相应的蛋白质表达、分泌和相互作用,从而为表型提供了一种机制解释。我们的研究扩展了ZP基因突变谱和表型,并进一步了解了ZP基因突变的体外致病机制。


The human zona pellucida (ZP) is an extracellular glycoprotein matrix composed of ZP1, ZP2, ZP3, and ZP4 surrounding the oocyte, and it plays an important role in sperm-egg interactions during fertilization. Structural and functional changes in the ZP can influence the process of fertilization and lead to female infertility. Previous studies have identified mutations in ZP1, ZP2, and ZP3 that lead to female infertility caused by oocyte degeneration, empty follicle syndrome, or in vitro fertilization failure. Here we describe seven patients from six independent families who had several abnormal oocytes or suffered from empty follicle syndrome, similar to the previously reported phenotypes. By whole-exome sequencing and Sanger sequencing, we identified several novel mutations in these patients. These included three homozygous mutations in ZP1 (c.1708G > A, p.Val570Met; c.1228C > T, p.Arg410Trp; c.507del, p.His170Ilefs*52), two mutations in a compound heterozygous state in ZP1 (c.1430 + 1G > T, p.Cys478X and c.1775-8T > C, p.Asp592Glyfs*29), a homozygous mutation in ZP2 (c.1115G > C, p.Cys372Ser), and a heterozygous mutation in ZP3 (c.763C > G, p.Arg255Gly). In addition, studies in CHO cells showed that the mutations in ZP1, ZP2, and ZP3 might affect the corresponding protein expression, secretion, and interaction, thus providing a mechanistic explanation for the phenotypes. Our study expands the spectrum of ZP gene mutations and phenotypes, and provides a further understanding of the pathogenic mechanism of ZP gene mutations in vitro.


获取全文 10.1007/s00439-019-01990-1