CHCHD10 variants in amyotrophic lateral sclerosis: Where is the evidence?

Annals of Neurology
Project MinE ALS Sequencing Consortium

Abstract

After the initial report of a CHCHD10 mutation in mitochondrial disease with features resembling amyotrophic lateral sclerosis (ALS), CHCHD10 mutations have been considered to be a frequent cause for ALS. However, the exact pathogenicity and clinical significance of these mutations remain unclear. Here, we aimed to determine the role of CHCHD10 mutations in ALS. We analyzed 4,365 whole genome sequenced ALS patients and 1,832 controls from 7 different countries and examined all nonsynonymous single nucleotide variants in CHCHD10. These were tested for association with ALS, independently and in aggregate using several genetic burden tests (including sequence kernel association test [SKAT], optimal unified test [SKAT-O], and Firth logistic regression). We identified 3 new variants in cases, but only 1 was ALS-specific. Also, 1 control-specific mutation was identified. There was no increased burden of rare coding mutations among ALS patients compared to controls (p = 0.86, p = 0.86, and p = 0.88 for SKAT, SKAT-O, and Firth, respectively). The few carriers with potential pathogenic CHCHD10 mutations exhibited a slowly progressive ALS-like phenotype with atypical features such as myopathy and deafness. CHCHD10 mutations seem to be a ...Continue Reading

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Citations

Feb 12, 2020·Neurology. Genetics·Julia L KeithLorne Zinman
Jul 10, 2019·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Rick A A van der SpekUNKNOWN Project MinE ALS Sequencing Consortium¶
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Aug 1, 2020·Frontiers in Neuroscience·Ramya RanganathanJanine Kirby
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May 1, 2021·International Journal of Molecular Sciences·Baojin Ding, Masood Sepehrimanesh
Jun 13, 2021·Neuroscience Letters·Elke BraemsLudo Van Den Bosch
Aug 4, 2021·Current Opinion in Neurology·Johnathan Cooper-KnockJan H Veldink

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