Mutation Screening of the CHCHD10 Gene in Chinese Patients with Amyotrophic Lateral Sclerosis

AbstractMutations in the coiled-coil-helix-coiled-coil-helix domain-containing protein 10 gene (CHCHD10), involved in mitochondrial function, have recently been reported as a causative gene of amyotrophic lateral sclerosis (ALS). The aim of this study was to obtain the mutation prevalence ofCHCHD10 and the phenotypes with mutations in Chinese ALS patients. A cohort of 499 ALS patients including 487 sporadic ALS (SALS) and 12 familial ALS (FALS), from the Department of Neurology, West China Hospital of Sichuan University, were screened for mutations of all exons of theCHCHD10 gene by Sanger sequencing. Novel candidate mutations or variants were confirmed by polymerase chain reaction-restriction fragment length polymorphism in 466 healthy individuals. All patients identified with mutations ofCHCHD10 gene were screened for mutations of the common ALS causative genes includingC9orf72,SOD1,TARDBP,FUS,PFN1, andSQSTM1. Three heterozygous variants, including two missense mutations (c.275A  >  G (p.Y92C) and c.306G >  C (p.Q102H)) and a synonymous change c.306G >  A (p.Q102Q), were found in exon 3 ofCHCHD10 in three alive SALS individuals (with the longest disease duration of 8.6  years), all of which were not detected in healthy controls. No mutation inCHCHD10 was identified in FALS patients. No mutation was found in the aforementioned common ALS causative genes in the patients who carriedCHCHD10 mutations. The mutation frequency ofCHCHD10 (0.4  %, 2/487) in a ...

Source: Molecular Neurobiology - May 24, 2017 Category: Neurology Source Type: research