CHCHD10mutations in Italian patients with sporadic amyotrophic lateral sclerosis: Figure 1

Sir, We read with interest the paper recently published in Brain (Bannwarth et al. , 2014) reporting a mutation in CHCHD10 (c.176C > T, p.Ser59Leu) in familial amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD). Interestingly, the mutated patients also showed signs of muscle mitochondrial pathology consisting of cytochrome c oxidase (COX)-negative fibres, ultrastructural mitochondrial abnormalities, impaired respiratory chain activity, and altered mitochondrial DNA (mtDNA) maintenance (multiple deletions). Additional CHCHD10 mutations were reported by Muller et al. (2014) who identified the c.44C > A variant (p.Arg15Leu) in two German familial ALS cases and the variant c.197C > A (p.Gly66Val) in a Finnish patient with familial motor neuron disease with predominant lower motor neuron involvement. Chaussenot et al. (2014) screened CHCHD10 in a cohort of 80 French patients with sporadic FTD-ALS, disclosing the p.Pro34Ser mutation in two independent subjects. Mutated patients also featured sensorineural hypoacusia typically associated with mitochondrial disease, but mitochondrial dysfunction was not formally documented. Finally Johnson et al. (2014) investigated 85 independent North American cases with familial ALS, reporting the p.Arg15Leu mutation in three of them. Here we report clinical, biochemical, and molecular findings of an Italian patient affected by sporadic early-onset ALS and muscle mitochondrial pathology associated with a novel CHCHD10 mutation. Moreover we investigated a cohort of Italian sporadic ALS patients, supporting the modest, but not negligible causative role of CHCHD10 variations. We previously found severe histochemical COX deficiency in 7 of 50 muscle biopsies from patients with sporadic ALS (Crugnola et al. , 2010). Sequence analysis of ALS-related genes was negative in all patients but two (SOD1: p.Gln22Arg and TDP43: p.Ala382Thr). We sequenced CHCHD10 coding regions in the remaining five patients, disclosing the novel heterozygous transition c.239C > T in exon 2, resulting in the amino acid change p.Pro80Leu, in one of them (Fig. 1 …