Homozygous Mutations in BTG4 Cause Zygotic Cleavage Failure and Female Infertility

合子 不育 遗传学 生物 劈理(地质) 男科 医学 基因 怀孕 胚胎发生 断裂(地质) 古生物学
作者
Wei Zheng,Zhou Zhou,Qian-Qian Sha,Xiangli Niu,Xiaoxi Sun,Juanzi Shi,Lei Zhao,Shuoping Zhang,Jing Dai,Sufen Cai,Fei Meng,Liang Hu,Fei Gong,Xiaoran Li,Jing Fu,Rong Shi,Guangxiu Lu,Biaobang Chen,Heng-Yu Fan,Lei Wang,Ge Lin,Qing Sang
出处
期刊:American Journal of Human Genetics [Elsevier]
卷期号:107 (1): 24-33 被引量:40
标识
DOI:10.1016/j.ajhg.2020.05.010
摘要

Zygotic cleavage failure (ZCF) is a unique early embryonic phenotype resulting in female infertility and recurrent failure of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). With this phenotype, morphologically normal oocytes can be retrieved and successfully fertilized, but they fail to undergo cleavage. Until now, whether this phenotype has a Mendelian inheritance pattern and which underlying genetic factors play a role in its development remained to be elucidated. B cell translocation gene 4 (BTG4) is a key adaptor of the CCR4-NOT deadenylase complex, which is involved in maternal mRNA decay in mice, but no human diseases caused by mutations in BTG4 have previously been reported. Here, we identified four homozygous mutations in BTG4 (GenBank: NM_017589.4 ) that are responsible for the phenotype of ZCF, and we found they followed a recessive inheritance pattern. Three of them—c.73C>T (p.Gln25Ter), c.1A>G (p.?), and c.475_478del (p.Ile159LeufsTer15)—resulted in complete loss of full-length BTG4 protein. For c.166G>A (p.Ala56Thr), although the protein level and distribution of mutant BTG4 was not altered in zygotes from affected individuals or in HeLa cells, the interaction between BTG4 and CNOT7 was abolished. In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF. Thus, we provide evidence that ZCF is a Mendelian phenotype resulting from mutations in BTG4. These findings contribute to our understanding of the role of BTG4 in human early embryonic development and provide a genetic marker for female infertility.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
文静的雨筠完成签到 ,获得积分10
刚刚
光脚丫完成签到,获得积分10
1秒前
无辜的兔子完成签到,获得积分10
1秒前
逐梦ing完成签到,获得积分10
2秒前
萌萌完成签到,获得积分10
3秒前
张瑞雪完成签到 ,获得积分10
4秒前
朝晖夕阴完成签到,获得积分10
6秒前
柳冰清完成签到 ,获得积分10
6秒前
kitty发布了新的文献求助10
7秒前
eternal_dreams完成签到 ,获得积分10
7秒前
怕黑盼山完成签到,获得积分10
7秒前
温暖宛筠完成签到,获得积分10
7秒前
丁老三完成签到,获得积分10
7秒前
张三完成签到 ,获得积分10
8秒前
易吴鱼完成签到 ,获得积分10
10秒前
skepticalsnails完成签到,获得积分10
11秒前
小斯完成签到,获得积分10
12秒前
蛋挞蛋挞完成签到,获得积分10
12秒前
猪猪比特完成签到,获得积分10
12秒前
精明的尔丝完成签到 ,获得积分10
13秒前
在水一方应助书生采纳,获得10
13秒前
14秒前
寒霁完成签到,获得积分10
15秒前
yicheng完成签到,获得积分10
15秒前
我我我完成签到,获得积分10
16秒前
17秒前
康康完成签到,获得积分10
18秒前
不见花绚丽完成签到,获得积分10
18秒前
ttkd11完成签到,获得积分10
18秒前
精明的尔丝关注了科研通微信公众号
18秒前
OeO完成签到 ,获得积分10
20秒前
GOD伟完成签到,获得积分10
20秒前
打打应助文献小松鼠采纳,获得10
20秒前
luluyang发布了新的文献求助10
21秒前
lll发布了新的文献求助10
21秒前
PeGe完成签到,获得积分10
22秒前
莫若舞完成签到,获得积分10
22秒前
zzt完成签到,获得积分10
22秒前
dd完成签到,获得积分10
22秒前
23秒前
高分求助中
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Chen Hansheng: China’s Last Romantic Revolutionary 500
宽禁带半导体紫外光电探测器 388
Case Research: The Case Writing Process 300
Global Geological Record of Lake Basins 300
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3142849
求助须知:如何正确求助?哪些是违规求助? 2793788
关于积分的说明 7807722
捐赠科研通 2450106
什么是DOI,文献DOI怎么找? 1303653
科研通“疑难数据库(出版商)”最低求助积分说明 627017
版权声明 601350