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Kathrin Müller, Peter M. Andersen, Annemarie Hübers, Nicolai Marroquin, Alexander E. Volk, Karin M. Danzer, Thomas Meitinger, Albert C. Ludolph, Tim M. Strom, Jochen H. Weishaupt, Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease, Brain, Volume 137, Issue 12, December 2014, Page e309, https://doi.org/10.1093/brain/awu227
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Sir,
Recently, Bannwarth et al. (2014) reported a family with a mitochondrial DNA instability disorder that variably presented with cerebellar ataxia and myopathy but also with an ALS-FTD-like phenotype. A mutation in CHCHD10, which codes for the mitochondrially located coiled-coil-helix-coiled-coil-helix domain-containing protein 10, was identified by whole exome sequencing as the likely cause of disease in this family. Conceptually, this is an interesting finding, as it shows for the first time that mutation of a gene coding for a mitochondrial protein and subsequent mitochondrial dysfunction can be a primary cause of amyotrophic lateral sclerosis (ALS). To date, single nucleotide polymorphisms in the gene for the regulator of mitochondrial biogenesis PGC-1α were described to have a disease-modifying effect in ALS (Eschbach et al., 2013).
The most important genetic evidence for the causality of mutant CHCHD10 presented by Bannwarth et al. is a p.Ser59Leu variant in this gene co-segregating with disease in one family. Moreover, the same variant was found in a patient of another ALS-FTD family. Lack of further DNA samples precluded segregation analysis in this family. Co-segregation in several families is desirable to firmly establish a novel disease gene. We are therefore pleased to present here additional genetic support for CHCHD10 as a novel ALS gene, and extend the phenotype/genotype correlation of CHCHD10-related neurodegeneration.
