Novel mutation in the ZP1 gene and clinical implications
Novel mutation in the ZP1 gene and clinical implications
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ZP1 基因的新突变及其临床意义
DOI：
10.1007/s10815-019-01404-1
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发表时间：
2019-02
影响因子：
3.1
通讯作者：
Wang Wenjun
中科院分区：
文献类型：
--
作者：
Yuan Ping;Li Ruiqi;Li Di;Zheng Lingyan;Ou Songbang;Zhao Haijing;Zhang Qingxue;Wang Wenjun
目的：空卵泡综合征（EFS）是一种复杂的生殖障碍，其特征是体外受精（IVF）过程中从成熟卵泡中反复吸出卵母细胞失败。除了一些由医源性问题和已知遗传因素引起的病例外，EFS还有许多无法解释的方面。在这里，我们旨在评估两名EFS患者的临床和遗传特征。方法：我们对来自中国一个非近亲家庭的2例原发性不孕症EFS患者进行了研究。两例患者均表现出相似的临床表型，即在卵泡发育正常、E2水平和生物可利用hCG血浆水平正常的重复周期中，少量颗粒细胞但未检出卵母细胞。在多个试管婴儿周期中获得一次或两次异常卵母细胞。我们对患者的LHCGR和ZP1~ZP4基因进行Sanger测序，并进一步进行生物信息学分析，以确定基因中的致病因子。结果：在患者2中发现了一种新的突变，c.181C>T （p.a g61cys）和一种已知的突变，c.1169_1176delTTTTCCCA (p.a ile390thrfs *16)，但在患者1中未发现突变。从她母亲那里遗传的新突变在对照队列和ExAc数据库中都不存在。精氨酸残基在这个位置是保守的，用半胱氨酸取代它被预测是有害的。在另一个等位基因中，预计父本移码突变会引入过早终止密码子，导致ZP1蛋白c端缺失234个氨基酸。结论：ZP1基因复合杂合突变与EFS和卵母细胞异常相关，为EFS的遗传基础和不育个体的遗传诊断提供了新的证据。
Purpose:Empty follicle syndrome (EFS) is a complex reproductive disorder characterized by the repeated failure to aspirate oocytes from mature ovarian follicles during in vitro fertilization (IVF). In addition to some cases caused by iatrogenic problems and known genetic factors, there are still many unexplained aspects of EFS. Here, we aimed to assess the clinical and genetic characteristics of two EFS patients.Methods:We have characterized two primary infertility patients with EFS in a nonconsanguineous family from China. Both the patients presented similar clinical phenotypes, that is a few granulosa cells but no oocytes could be retrieved during repeated cycles with normal follicular development, E2 levels, and bioavailable hCG plasma levels. Abnormal oocytes were obtained once or twice between multiple IVF cycles. We performed Sanger sequencing of the LHCGR and ZP1~ZP4 genes in the patients, and further bioinformatics analysis was performed to identify pathogenic elements in the genes.Results:A novel mutation, c.181C>T (p.Arg61Cys), and a known mutation, c.1169_1176delTTTTCCCA (p.Ile390Thrfs*16), in the ZP1 gene were both identified in patient 2, but no mutations were identified in patient 1. The novel mutation inherited from her mother was absent in the control cohort and the ExAc database. The arginine residue is conserved at this position, and its replacement by cysteine was predicted to be deleterious. In another allele, a paternal frameshift mutation was predicted to introduce premature stop codons, resulting in the deletion of 234 amino acids from the C-terminus of the ZP1 protein.Conclusions:Our findings presented compound heterozygous mutations in ZP1 associated with EFS and abnormal oocytes and provided further new evidence for the genetic basis of EFS and support for the genetic diagnosis of infertile individuals.
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影响因子：
4.6
作者：
T. Rankin;Prue Talbot;Eric Lee;J. Dean
通讯作者：
T. Rankin;Prue Talbot;Eric Lee;J. Dean
影响因子：
6.1
作者：
Vujisic, S;Stipoljev, F;Jezek, D
通讯作者：
Jezek, D
影响因子：
4.6
作者：
T. Rankin;M. O'Brien;Eric Lee;K. Wigglesworth;J. Eppig;Jurrien Dean
通讯作者：
T. Rankin;M. O'Brien;Eric Lee;K. Wigglesworth;J. Eppig;Jurrien Dean
影响因子：
0.7
作者：
Wassarman, Paul M.;Litscher, Eveline S.
通讯作者：
Litscher, Eveline S.
DOI：
10.1083/jcb.71.2.680
发表时间：
1976-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Anderson E;Albertini DF
通讯作者：
Albertini DF