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
细腻的铁身完成签到,获得积分10
1秒前
在水一方应助肉肉小白采纳,获得10
1秒前
体贴的叛逆者完成签到,获得积分10
1秒前
九月清晨发布了新的文献求助10
3秒前
大方的若山应助冷酷思远采纳,获得10
3秒前
欣喜的薯片完成签到 ,获得积分10
3秒前
昵称完成签到,获得积分10
6秒前
慕容博完成签到 ,获得积分10
6秒前
感动归尘应助燕子采纳,获得10
7秒前
觅兴完成签到,获得积分0
7秒前
8秒前
leezhen完成签到,获得积分10
8秒前
Akim应助Tici采纳,获得10
9秒前
qiqi完成签到,获得积分10
9秒前
9秒前
10秒前
shijin135完成签到,获得积分10
12秒前
袁硕完成签到 ,获得积分10
13秒前
丿淘丶Tao丨完成签到,获得积分10
15秒前
Jingg完成签到,获得积分10
15秒前
淀粉肠完成签到 ,获得积分10
15秒前
文艺的初南完成签到 ,获得积分10
16秒前
肉肉小白发布了新的文献求助10
16秒前
ssssYyyy完成签到 ,获得积分10
17秒前
呆呆完成签到 ,获得积分10
18秒前
NexusExplorer应助邵翎365采纳,获得10
18秒前
希望天下0贩的0应助mm采纳,获得10
18秒前
九月清晨完成签到 ,获得积分10
20秒前
小丸子呀完成签到 ,获得积分10
20秒前
经竺发布了新的文献求助10
21秒前
无敌鱼完成签到,获得积分20
23秒前
Ricardo完成签到 ,获得积分10
25秒前
嘟嘟请让一让完成签到,获得积分10
26秒前
fantexi113完成签到,获得积分10
26秒前
FashionBoy应助淡然篮球采纳,获得10
28秒前
Even9完成签到,获得积分10
29秒前
蔡蔡完成签到,获得积分10
31秒前
经竺发布了新的文献求助10
32秒前
32秒前
蓝璃完成签到,获得积分10
32秒前
高分求助中
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
Retention of title in secured transactions law from a creditor's perspective: A comparative analysis of selected (non-)functional approaches 500
"Sixth plenary session of the Eighth Central Committee of the Communist Party of China" 400
Introduction to Modern Controls, with illustrations in MATLAB and Python 310
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 3056768
求助须知:如何正确求助?哪些是违规求助? 2713267
关于积分的说明 7435318
捐赠科研通 2358312
什么是DOI,文献DOI怎么找? 1249347
科研通“疑难数据库(出版商)”最低求助积分说明 607030
版权声明 596259