桑格测序
发病机制
GNAQ公司
外显子组测序
遗传学
突变
癌症研究
生殖系
种系突变
基因
生物
免疫学
作者
Jie Yin,Zhongping Qin,Kai Wu,Yong Zhu,Landian Hu,Xiangyin Kong
出处
期刊:Combinatorial Chemistry & High Throughput Screening
[Bentham Science]
日期:2020-01-16
卷期号:22 (10): 675-682
被引量:2
标识
DOI:10.2174/1386207322666191203110042
摘要
Backgrounds and Objective: Blue rubber bleb nevus syndrome (BRBN) or Bean syndrome is a rare Venous Malformation (VM)-associated disorder, which mostly affects the skin and gastrointestinal tract in early childhood. Somatic mutations in TEK have been identified from BRBN patients; however, the etiology of TEK mutation-negative patients of BRBN need further investigation. Method: Two unrelated sporadic BRBNs and one sporadic VM were firstly screened for any rare nonsilent mutation in TEK by Sanger sequencing and subsequently applied to whole-exome sequencing to identify underlying disease causative variants. Overexpression assay and immunoblotting were used to evaluate the functional effect of the candidate disease causative variants. Results: In the VM case, we identified the known causative somatic mutation in the TEK gene c.2740C>T (p.Leu914Phe). In the BRBN patients, we identified two rare germline variants in GLMN gene c.761C>G (p.Pro254Arg) and c.1630G>T(p.Glu544*). The GLMN-P254R-expressing and GLMN-E544X-expressing HUVECs exhibited increased phosphorylation of mTOR-Ser-2448 in comparison with GLMN-WTexpressing HUVECs in vitro. Conclusion: Our results demonstrated that rare germline variants in GLMN might contribute to the pathogenesis of BRBN. Moreover, abnormal mTOR signaling might be the pathogenesis mechanism underlying the dysfunction of GLMN protein.
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