小柯机器人

美国凤凰城儿童医院Michael C. Kruer研究团队发现神经发生基因的突变可增加脑瘫风险。该研究于2020年9月28日发表于国际一流学术期刊《自然—遗传学》。

Title: Mutations disrupting neuritogenesis genes confer risk for cerebral palsy

Author: Sheng Chih Jin, Sara A. Lewis, Somayeh Bakhtiari, Xue Zeng, Michael C. Sierant, Sheetal Shetty, Sandra M. Nordlie, Aureliane Elie, Mark A. Corbett, Bethany Y. Norton, Clare L. van Eyk, Shozeb Haider, Brandon S. Guida, Helen Magee, James Liu, Stephen Pastore, John B. Vincent, Janice Brunstrom-Hernandez, Antigone Papavasileiou, Michael C. Fahey, Jesia G. Berry, Kelly Harper, Chongchen Zhou, Junhui Zhang, Boyang Li, Jennifer Heim, Dani L. Webber, Mahalia S. B. Frank, Lei Xia, Yiran Xu, Dengna Zhu, Bohao Zhang, Amar H. Sheth, James R. Knight, Christopher Castaldi, Irina R. Tikhonova, Francesc Lpez-Girldez, Boris Keren, Sandra Whalen, Julien Buratti, Diane Doummar, Megan Cho, Kyle Retterer, Francisca Millan, Yangong Wang, Jeff L. Waugh, Lance Rodan, Julie S. Cohen, Ali Fatemi, Angela E. Lin, John P. Phillips, Timothy Feyma, Suzanna C. MacLennan, Spencer Vaughan, Kylie E. Crompton, Susan M. Reid, Dinah S. Reddihough, Qing Shang, Chao Gao, Iona Novak, Nadia Badawi, Yana A. Wilson, Sarah J. McIntyre, Shrikant M. Mane, Xiaoyang Wang, David J. Amor, Daniela C. Zarnescu, Qiongshi Lu

Issue&Volume: 2020-09-28

Abstract: In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent–offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.

DOI: 10.1038/s41588-020-0695-1

Source: https://www.nature.com/articles/s41588-020-0695-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex