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MT-CO1 variants have been implicated in a case of early-onset Leigh syndrome with profound cytochrome c oxidase (complex IV) deficiency. In the reported patient, muscle biopsy at 2 years 5 months revealed markedly decreased complex IV activity and loss of COX1 subunits across multiple tissues, while other respiratory chain complexes remained relatively intact (PMID:2159985). No additional unrelated probands or familial segregation data have been described to date.
Functional characterization demonstrates that MT-CO1 disruption leads to deficient oxidative phosphorylation: patient tissues and model systems show reduced oxygen consumption, impaired ATP synthesis, elevated lactate, and destabilization of complex IV assembly, mirroring the clinical Leigh phenotype. These data provide moderate experimental support but, in the absence of multiple genetic observations or segregation, the overall genetic evidence is limited.
Key Take-home: MT-CO1 should be included in mitochondrial gene panels for infants with Leigh syndrome and isolated complex IV deficiency.
Gene–Disease AssociationLimitedSingle LS proband with MT-CO1-related CCO deficiency; no recurrent variants or segregation Genetic EvidenceLimitedEvidence restricted to one case report without additional unrelated probands Functional EvidenceModerateConcordant biochemical and cellular assays demonstrating complex IV impairment |