Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterised by the degeneration of both upper and lower motor neurons. Although most cases occur as sporadic ALS (sALS), approximately 5%–10% of patients with ALS have a family history of ALS (fALS).1

More than 20 potential genes have been identified as ALS-related genes so far, and the function of these causative genes can be loosely grouped into three categories: RNA metabolism, cytoskeletal dynamics and protein homeostasis.1 However, genetic heterogeneity among different ethnic background exists.

The kinesin family member 5A (KIF5A), composed of an N-terminal motor domain, a coiled-coil stalk region and a C-terminal cargo binding domain, is a member of the kinesin superfamily proteins (KIFs) and is involved in the axonal transport.2 Recently, two independent studies found that splice site mutations in the C-terminal cargo binding domain of KIF5A can cause fALS in the Caucasian ALS population,3 4 and the functional studies elucidated that splice site mutations can cause exon skipping and lead to the loss of RNA expression, which suggest that haploinsufficiency is the most likely underlying molecular mechanism.3 4 In this context, we aimed to reveal the mutation frequency of the C-terminal cargo binding domain in KIF5A in a large cohort of Chinese patients with ALS.