A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis

生物 核孔蛋白 遗传学 错义突变 突变 嵌合体 细胞生物学 内科学 基因 核蛋白 医学 转录因子
作者
Ariella Weinberg‐Shukron,Paul Renbaum,Rachel Kalifa,Sharon Zeligson,Ziva Ben‐Neriah,Amatzia Dreifuss,Amal Abu Rayyan,Noa Maatuk,Nilly Fardian,Dina Rekler,Moien Kanaan,Abraham O. Samson,Ephrat Levy‐Lahad,Offer Gerlitz,David Zangen
出处
期刊:Journal of Clinical Investigation [American Society for Clinical Investigation]
卷期号:125 (11): 4295-4304 被引量:96
标识
DOI:10.1172/jci83553
摘要

Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
hlt完成签到 ,获得积分10
1秒前
fang发布了新的文献求助10
1秒前
1秒前
codwest完成签到,获得积分10
4秒前
Ssyong发布了新的文献求助10
5秒前
Lin完成签到,获得积分10
6秒前
量子星尘发布了新的文献求助10
6秒前
粗犷的灵松完成签到 ,获得积分10
6秒前
善学以致用应助Xshif采纳,获得10
7秒前
9秒前
9秒前
科研通AI6应助务实凡灵采纳,获得20
9秒前
勤劳善良的胖蜜蜂给勤劳善良的胖蜜蜂的求助进行了留言
10秒前
fugu0完成签到,获得积分10
11秒前
11秒前
qiao完成签到,获得积分10
12秒前
随风发布了新的文献求助10
13秒前
挞挞不要胖完成签到 ,获得积分10
13秒前
13秒前
奢侈的温馨问候完成签到,获得积分10
13秒前
完美世界应助sharon采纳,获得10
14秒前
ding应助Yvonne采纳,获得10
15秒前
宋世伟发布了新的文献求助10
15秒前
平常的猫咪完成签到,获得积分10
15秒前
16秒前
18秒前
19秒前
20秒前
传奇3应助宋世伟采纳,获得10
20秒前
希望天下0贩的0应助luojun采纳,获得10
21秒前
21秒前
完美世界应助Wangrich采纳,获得10
22秒前
王讯完成签到,获得积分10
24秒前
qiao发布了新的文献求助10
25秒前
量子星尘发布了新的文献求助10
26秒前
28秒前
Lucien应助Ssyong采纳,获得10
29秒前
29秒前
29秒前
lascqy完成签到 ,获得积分10
30秒前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Разработка технологических основ обеспечения качества сборки высокоточных узлов газотурбинных двигателей,2000 1000
Nuclear Fuel Behaviour under RIA Conditions 500
Life: The Science of Biology Digital Update 400
Why America Can't Retrench (And How it Might) 400
Another look at Archaeopteryx as the oldest bird 390
Optimization and Learning via Stochastic Gradient Search 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 物理化学 基因 催化作用 遗传学 冶金 电极 光电子学
热门帖子
关注 科研通微信公众号,转发送积分 4686712
求助须知:如何正确求助?哪些是违规求助? 4060352
关于积分的说明 12553545
捐赠科研通 3757326
什么是DOI,文献DOI怎么找? 2075068
邀请新用户注册赠送积分活动 1103913
科研通“疑难数据库(出版商)”最低求助积分说明 983021