TBK1 mutations in Italian patients with amyotrophic lateral sclerosis: genetic and functional characterisation.

ABSTRACT:

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 pre

SUBMITTER: Pozzi L 

PROVIDER: S-EPMC5629935 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature