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Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy.
- Source :
-
Human mutation [Hum Mutat] 2022 Dec; Vol. 43 (12), pp. 1970-1978. Date of Electronic Publication: 2022 Sep 07. - Publication Year :
- 2022
-
Abstract
- Primary mitochondrial diseases are a group of genetically and clinically heterogeneous disorders resulting from oxidative phosphorylation (OXPHOS) defects. COX11 encodes a copper chaperone that participates in the assembly of complex IV and has not been previously linked to human disease. In a previous study, we identified that COX11 knockdown decreased cellular adenosine triphosphate (ATP) derived from respiration, and that ATP levels could be restored with coenzyme Q <subscript>10</subscript> (CoQ <subscript>10</subscript> ) supplementation. This finding is surprising since COX11 has no known role in CoQ <subscript>10</subscript> biosynthesis. Here, we report a novel gene-disease association by identifying biallelic pathogenic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated families using trio genome and exome sequencing. Functional studies showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ <subscript>10</subscript> . These results not only suggest that COX11 variants cause defects in energy production but reveal a potential metabolic therapeutic strategy for patients with COX11 variants.<br /> (© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)
- Subjects :
- Humans
Mitochondria metabolism
Adenosine Triphosphate metabolism
Copper Transport Proteins metabolism
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
Electron Transport Chain Complex Proteins metabolism
Mitochondrial Encephalomyopathies genetics
Mitochondrial Encephalomyopathies metabolism
Mitochondrial Diseases genetics
Mitochondrial Diseases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 43
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 36030551
- Full Text :
- https://doi.org/10.1002/humu.24453