Late onset spinal motor neuronopathy is caused by mutation in CHCHD10

Abstract

Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems.

Evolving neuromuscular phenotype in a patient with a heterozygous CHCHD10 p.G66V mutation

“…The patient is still ambulant at the age of 62 years without walking aids. We identified the LOSMoN/SMAJ mutation pG66V in the CHCHD10 gene in this patient, thus confirming the final diagnosis [1].…”

“…In some cases, such a diagnostic odyssey may lead to harmful treatments or to misguided and far-reaching decisions by the patient. We report on a male patient with lateonset spinal motor neuronopathy (LOSMoN/SMAJ [1], OMIM #615048) with three different clinical diagnoses during the disease course.…”

IsCHCHD10Pro34Ser pathogenic for frontotemporal dementia and amyotrophic lateral sclerosis?: Figure 1

“…Subsequent reports have identified CHCHD10 variants in other FTD-ALS patients (Chaussenot et al, 2014), as well as those with pure ALS (Johnson et al, 2014;Mü ller et al, 2014;Ronchi et al, 2014), mitochondrial myopathy (Ajroud-Driss et al, 2015) and spinal motor neuronopathy (Penttilä et al, 2015). Seven different amino acid substitutions have been identified, all arising in exon 2, and the prevalence of CHCHD10 variants is estimated at 1.4-3.5% in ALS or FTD-ALS spectrum cases of European ancestry.…”

Mutation analysis ofCHCHD10in different neurodegenerative diseases

“…Affected family members were presented with a complex phenotype that included symptoms of amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), cerebellar ataxia, Parkinson's disease and a mitochondrial myopathy associated with multiple mitochondrial DNA deletions. So far, seven missense CHCHD10 mutations have been reported in patients with a broad phenotypic range, including ALS/FTLD (p.S59L and p.P34S) Chaussenot et al, 2014), ALS (p.R15L and p.G66V) (Johnson et al, 2014;Muller et al, 2014), myopathy (p.R15S and p.G58R) (Ajroud-Driss et al, 2015) and lateonset spinal motor neuronopathy (p.G66V) (Penttila et al, 2015). All of them affect exon 2 (a mutational hotspot of CHCHD10).…”