Mitochondrial disease

Gene: CHCHD10

Green List (high evidence)

CHCHD10 is a small protein of the mitochondrial intermembrane space that is enriched at cristae junctions. It is predicted to be involved in oxidative phosphorylation or in maintenance of cristae morphology. Variants have been associated with a broad spectrum of neurological/neuromuscular phenotypes. Several large multiplex families described segregating different neurological disorders, ranging from dementia, to SMA, to myopathy. The p.Gly66Val variant is a founder variant in the Finnish population, associated with the SMA, Jokela type phenotype. Overall, CHCHD10 appears to be a very rare cause of dementia/ALS, no cases identified in a large cohort reported in PMID 31690696. Some suggestion that variants may act through a GoF rather than LoF mechanism. Multiple lines of functional data supporting gene-disease association.

Created: 1 Sep 2020, 10:07 p.m. | Last Modified: 1 Sep 2020, 10:07 p.m.

Panel Version: 0.471

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 615911; Spinal muscular atrophy, Jokela type 615048; Myopathy, isolated mitochondrial, autosomal dominant 616209

Publications

• 24934289
• 25428574
• 25193783
• 32042922
• 31690696
• 30877432
• 30874923
• 31261376

Mode of pathogenicity
Other

PMID: 31261376 - Xiao - functional studies on CHCHD10. They find that it is highly expressed at the postsynapse of neuromuscular junctions (NMJ) in skeletal muscles. Knockout of CHCHD10 in mice resulted in motor defects, abnormal neuromuscular transmission and NMJ structure. They report that mitochondrial CHCHD10 is required for ATP production at NMJs by promoting AChRs gene expression.

Created: 1 Sep 2020, 1:31 p.m. | Last Modified: 1 Sep 2020, 1:31 p.m.

Panel Version: 0.4091

Publications

• 31261376