作者
Laura Pozzi, Fabiola Valenza, Lorena Mosca, Andrea Dal Mas, Teuta Domi, Alessandro Romano, Claudia Tarlarini, Yuri Matteo Falzone, Lucio Tremolizzo, Gianni Sorarù, Federica Cerri, Pilar M Ferraro, Silvia Basaia, Federica Agosta, Raffaella Fazio, Mauro Comola, Giancarlo Comi, Maurizio Ferrari, Angelo Quattrini, Christian Lunetta, Silvana Penco, Dario Bonanomi, Paola Carrera, Nilo Riva
发表日期
2017/10/1
期刊
Journal of Neurology, Neurosurgery & Psychiatry
卷号
88
期号
10
页码范围
869-875
出版商
BMJ Publishing Group Ltd
简介
Background
TANK-binding kinase 1 (TBK1) gene has been recently identified as a causative gene of amyotrophic lateral sclerosis (ALS).
Methods
We sequenced the TBK1 gene in a cohort of 154 Italian patients with ALS with unclear genetic aetiology. We subsequently assessed the pathogenic potential of novel identified TBK1 variants using functional in vitro studies: expression, targeting and activity were evaluated in patient-derived fibroblasts and in cells transfected with mutated-TBK1 plasmids.
Results
We identified novel genomic TBK1 variants including two loss-of-function (LoF) (p.Leu59Phefs*16 and c.358+5G>A), two missense (p.Asp118Asn and p.Ile397Thr) and one intronic variant (c.1644–5_1644-2delAATA), in addition to two previously reported pathogenetic missense variants (p.Lys291Glu and p.Arg357Gln). Functional studies in patient-derived fibroblasts revealed that the c.358+5G>A causes aberrant …
学术搜索中的文章
L Pozzi, F Valenza, L Mosca, A Dal Mas, T Domi… - Journal of Neurology, Neurosurgery & Psychiatry, 2017