Reply: High prevalence of CHCHD10 mutations in patients with frontotemporal dementia from China

Sir, Data recently published in Brain indicate that the CHCHD10 gene (NM_213720.2) plays an important role in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) (Bannwarth et al. , 2014; Johnson et al. , 2014; Muller et al. , 2014; Dols-Icardo et al. , 2015; Marroquin et al. , 2015). The CHCHD10 gene is located on chromosome 22q.11.23 and encodes a protein enriched at cristae junctions in mitochondria. Mutations in this gene cause mitochondrial dysfunction, which leads to disease. The study is the first report proposing that mitochondrial dysfunction contributes to the pathogenesis of ALS and FTD. The prevalence of the CHCHD10 mutation has been reported in a number of nationalities, including German (2.3%), French (2.6%), Spanish (0.68%) and Italian (1%) populations (Chaussenot et al. , 2014; Muller et al. , 2014; Chio et al. , 2015; Dols-Icardo et al. , 2015). However, no mutation analysis has been performed in Asian populations, and most variants have been on the ALS or ALS-FTD spectrum. Here, we present data showing that the CHCHD10 mutation is common in patients with the pure FTD phenotype in China. Patients with ALS ( n = 165) and FTD ( n = 65) were recruited at the outpatient clinic of Xiangya Hospital, China. The patients with ALS did not have mutations in SOD1 , FUS , C9orf72 and TARDBP . Additionally, the patients with FTD did not have any variants of MAPT , GRN and C9orf72 . We screened all of the exons in the CHCHD10 gene using Sanger sequencing. The analyses also included 500 unaffected individuals with matched geographical ancestry as healthy controls. This study was approved by the ethics committee of Xiangya Hospital, Central South University in China. …