一例疑似家族性肌萎缩侧索硬化症病例中FUS基因的新生无义突变。
De novo nonsense mutation of the FUS gene in an apparently familial amyotrophic lateral sclerosis case.
作者信息
Calvo Andrea, Moglia Cristina, Canosa Antonio, Brunetti Maura, Barberis Marco, Traynor Bryan J, Carrara Giovanna, Valentini Consuelo, Restagno Gabriella, Chiò Adriano
机构信息
"Rita Levi Montalcini" Department of Neuroscience, ALS Center, University of Torino, Torino, Italy.
Laboratory of Molecular Genetics, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
出版信息
Neurobiol Aging. 2014 Jun;35(6):1513.e7-11. doi: 10.1016/j.neurobiolaging.2013.12.028. Epub 2013 Dec 27.
Abstract
Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two-third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently familial ALS. This mutation causes a phenotype characterized by a young age at onset, a rapid course (<24 months), and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes.
摘要
C9ORF72、SOD1、TARDBP和FUS基因的突变约占家族性肌萎缩侧索硬化症（ALS）病例的三分之二以及散发性ALS病例的5%。我们报告了首例携带FUS基因第14外显子新发无义突变（c.1483c>t；p.R495X）且临床表现为明显家族性ALS的患者。该突变导致的表型特点为发病年龄较轻、病程进展迅速（<24个月）、延髓起病且早期出现呼吸受累，以主要累及下运动神经元疾病为主。新发突变可能是相当一部分携带ALS相关基因突变的散发性ALS患者的病因。
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