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Mitochondrial disease v0.1104 MT-CO1 Zornitza Stark Phenotypes for gene: MT-CO1 were changed from Leber's optic atrophy; Sideroblastic anaemia; Cytochrome c oxidase deficiency; Myoglobinuria to Mitochondrial respiratory chain complex deficiency, MONDO:0000066, MT-CO1-related
Mitochondrial disease v0.1103 MT-CO1 Zornitza Stark Publications for gene: MT-CO1 were set to 30743023; 39460813; 24956508
Mitochondrial disease v0.1102 MT-CO1 Zornitza Stark edited their review of gene: MT-CO1: Added comment: DEFINITIVE by ClinGen for mitochondrial disease.

At least eight variants (m.5920G>A, m.6328C>T, m.6579G>A, m.6597C>A, m.6698del, m.6708G>A, m.6930G>A, m.7402del) have been reported in eight individuals across multiple publications. Single fiber testing and cybrid analyses supported the pathogenicity of several of these variants. Age of onset in affected individuals ranged from infancy to adolescence. Clinical features included Leigh syndrome, cognitive decline, exercise intolerance, myoglobinuria, stroke-like episodes, myoclonic epilepsy, cerebellar ataxia, muscle weakness and atrophy, cataracts, optic atrophy, sensorineural hearing loss, and left ventricular hypertrophy. Brain imaging was variable and ranged from normal to findings consistent with LSS, cerebellar atrophy, and cortical atrophy. Muscle biopsies showed ragged red fibers, COX-deficient fibers, and complex IV deficiency. Metabolic laboratory investigations revealed normal to elevated lactate and creatine kinase (CK). Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed (61-95% in muscle, undetectable to 30% in blood, undetectable to 40% in skin fibroblasts, undetectable in hair follicles when tested, and 15-70% in urine).

The mechanism of pathogenicity appears to be loss of function resulting in specific loss of complex IV activity. This gene-disease relationship is also supported by known biochemical function, in vitro functional assays, and a mouse model, all of which demonstrate altered mitochondrial function as a result of variants in MT-CO1.; Changed publications: 30743023, 39460813, 24956508, 10441567, 10980727, 15751226, 16284789, 18977334, 22832341, 18276892, 30030519
Mitochondrial disease v0.1014 MT-CO1 Zornitza Stark Publications for gene: MT-CO1 were set to
Mitochondrial disease v0.1013 MT-CO1 Zornitza Stark edited their review of gene: MT-CO1: Changed publications: 30743023, 39460813, 24956508; Changed phenotypes: Mitochondrial respiratory chain complex deficiency, MONDO:0000066, MT-CO1-related
Mitochondrial disease v0.367 MT-CO1 Zornitza Stark Marked gene: MT-CO1 as ready
Mitochondrial disease v0.367 MT-CO1 Zornitza Stark Gene: mt-co1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.367 MT-CO1 Zornitza Stark Tag mtDNA tag was added to gene: MT-CO1.
Mitochondrial disease v0.367 MT-CO1 Zornitza Stark Classified gene: MT-CO1 as Green List (high evidence)
Mitochondrial disease v0.367 MT-CO1 Zornitza Stark Gene: mt-co1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.366 MT-CO1 Zornitza Stark gene: MT-CO1 was added
gene: MT-CO1 was added to Mitochondrial disease. Sources: Expert list
Mode of inheritance for gene gene: MT-CO1 was set to MITOCHONDRIAL
Phenotypes for gene: MT-CO1 were set to Leber's optic atrophy; Sideroblastic anaemia; Cytochrome c oxidase deficiency; Myoglobinuria
Review for gene: MT-CO1 was set to GREEN
Added comment: Sources: Expert list