外显子组测序
共济失调
表型
突变
周围神经病变
遗传学
生物
外显子组
医学
基因
内分泌学
神经科学
糖尿病
作者
Macarena Cabrera‐Serrano,David Coote,Dimitar N. Azmanov,Hayley Goullée,Erik Andersen,Catriona McLean,Mark Davis,Ryosuke Ishimura,Zornitza Stark,Jean‐Michel Vallat,Masaaki Komatsu,Andrew J. Kornberg,Monique M. Ryan,Nigel G. Laing,Gianina Ravenscroft
标识
DOI:10.1136/jmedgenet-2019-106496
摘要
Background UBA5 is the activating enzyme of UFM1 in the ufmylation post-translational modification system. Different neurological phenotypes have been associated with UBA5 pathogenic variants including epilepsy, intellectual disability, movement disorders and ataxia. Methods and results We describe a large multigenerational consanguineous family presenting with a severe congenital neuropathy causing early death in infancy. Whole exome sequencing and linkage analysis identified a novel homozygous UBA5 NM_024818.3 c.31C>T (p.Arg11Trp) mutation. Protein expression assays in mouse tissue showed similar levels of UBA5 in peripheral nerves to the central nervous system. CRISPR-Cas9 edited HEK (human embrionic kidney) cells homozygous for the UBA5 p.Arg11Trp mutation showed reduced levels of UBA5 protein compared with the wild-type. The mutant p.Arg11Trp UBA5 protein shows reduced ability to activate UFM1. Conclusion This report expands the phenotypical spectrum of UBA5 mutations to include fatal peripheral neuropathy.
科研通智能强力驱动
Strongly Powered by AbleSci AI