CHCHD10 Pro34Ser is not a highly penetrant pathogenic variant for amyotrophic lateral sclerosis and frontotemporal dementia.

Abstract

Sir, Recently, Bannwarth and colleagues reported that mutations in CHCHD10 were causative of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), with compelling segregation data and functional investigations well supporting these findings (Bannwarth et al. , 2014). In a number of follow-up studies, CHCHD10 was screened in ALS, FTD and other neurodegenerative disorder cohorts—including autosomal dominant mitochondrial myopathy and late-onset spinal motor neuronopathy—and novel putative disease-causing variants were identified (Chaussenot et al. , 2014; Johnson et al. , 2014; Muller et al. , 2014; Ajroud-Driss et al. , 2015; Chio et al. , 2015; Kurzwelly et al. , 2015; Penttila et al. , 2015; Ronchi et al. , 2015; Zhang et al. , 2015). In particular, one variant, the Pro34Ser in exon 2, was reported by three studies to be present in >1% of ALS and FTD cases in Caucasian populations (Chaussenot et al. , 2014; Chio et al. , 2015; Ronchi et al. , 2015). In the context of ALS, this is a remarkable finding and would make the CHCHD10 Pro34Ser variant …