Table 4.
Mutations associated with mitochondrial CIV deficiency. Adapted from [51].
| Gene/Protein | OMIM | Function | Reported Clinical Phenotypes |
|---|---|---|---|
| MT-CO1 | 516030 | Catalytic core subunit 1 | LHON, AISA, ataxia, hypotonia, and epilepsy |
| MT-CO2 | 516040 | Catalytic core subunit 2 | Optic atrophy, ataxia, myopathy, lactic acidosis, and cardiomyopathy |
| MT-CO3 | 516050 | Catalytic core subunit 3 | LHON, myoglobinuria, lactic acidosis, encephalopathy, tetraparesis, and myopathy |
| COX4I1 | 123864 | Subunit 4 isoform 1 | Poor growth, dysmorphism, Fanconi anaemia, and encephalopathy |
| COX4I2 | 607976 | Subunit 4 isoform 2 | Congenital exocrine pancreatic insufficiency |
| COX5A | 603773 | Subunit 5A | Pulmonary arterial hypertension, lactic acidosis, and failure to thrive |
| COX6A1 | 602072 | Subunit 6A isoform 1 | CMTRID |
| COX6A2 | 602009 | Subunit 6A isoform 2 | Myopathy |
| COX6B1 | 124089 | Subunit 6B isoform 1 | Encephalomyopathy, hypotonia, growth retardation, and lactic acidosis |
| COX7A1 | 123995 | Subunit 7A isoform 1 | Failure to thrive, encephalopathy, and hypotonia |
| COX7B | 300885 | Subunit 7B | MLS and MIDAS |
| COX8A | 123870 | Subunit 8A | Pulmonary hypertension, microcephaly, anddevelopmental delay |
| COXFA4 | 603933 | Subunit FA4 | Encephalopathy, dystonia, ataxia, and lactic acidosis |
| COX14 | 614478 | MT-CO1 stabilization | Encephalopathy, lactic acidosis, and respiratory distress |
| COA3 | 614775 | MT-CO1 stabilization | Exercise intolerance and peripheral neuropathy |
| TACO1 | 612958 | MT-CO1 translational activation | LD, optic atrophy, hypotonia, and tetraparesis |
| COX10 | 602125 | Heme A biogenesis | Ataxia, hypotonia, lactic acidosis, sensorineural loss, and Leigh syndrome |
| COX15 | 603646 | Heme A biogenesis | Cardioencephalomyopathy and LD |
| COX20 | 614698 | MT-CO2 stabilization | Growth retardation, hypotonia, cerebellar ataxia, and lactic acidosis |
| SCO1 | 603644 | CuA centre biogenesis | Encephalopathy, liver disease, hepatomegaly, lactic acidosis, and cardiac hypertrophy |
| SCO2 | 604272 | CuA centre biogenesis | Encephalo–cardiomyopathy |
| SURF1 | 185620 | Unknown | LD |
| COA5 | 613920 | Unknown | Cardiomyopathy |
| COA6 | 614772 | CuA centre biogenesis | Hypertrophic cardiomyopathy |
| COA7 | 615623 | Unknown | Encephalopathy and spinocerebellar ataxia |
| COA8 | 616003 | Unknown | Encephalopathy, cavitating dystrophy, tetraparesis, and ataxia |
| PET100 | 614770 | Unknown | LD and lactic acidosis |
| PET117 | 614771 | Unknown | Neurodevelopmental regression, exercise intolerance, and lactic acidosis |
| FASTKD2 | 612322 | mt-mRNAs stability | MELAS, brain atrophy, developmental delay, hemiparesis, and encephalomyopathy |
| LRPPRC | 607544 | mt-mRNAs stability | French-Canadian Leigh syndrome |