Table 5.
Complex IV variants
| Disease/clinical features | Variant | Subunit | AA change | Agea | % VAF | Complex IV | Reference | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Muscle | Blood | Fibroblasts | Other | Residual activity, % | Protein levels | ||||||
| Epilepsia partialis continua | 6489C > A | MT-CO1 | Leu196Ileu | 17 yr | 95 | 30 | 74, muscle | (Varlamov et al. 2002) | |||
| Rhabdomyolysis, myopathy | 6708G > A | MT-CO1 | Gly269X | 30 yr | 81–89 | <1 | 21, muscleb | ↓ | (Kollberg et al. 2005) | ||
| Multisystem mitochondrial disease | 6930G > A | MT-CO1 | Gly343X | 21 yr | 75 | 27 | 35, 65, cybrids 33, myoblasts |
10, muscle 50, cybrids with vaf of 35% 25, cybrids with vaf of 65% |
↓ | (Bruno et al. 1999) | |
| EXIT with mild intellectual disability | 6955G > A | MT-CO1 | Gly351Asp | 13 yr | 100 | 15, muscle | ↓ | (Herrero-Martin et al. 2008) | |||
| McArdle's syndrome | 7444G > A | MT-CO1 | X514Lys | 57 yr | 100 | 35, muscle | (Aguilera Garcia-Lozano et al. 2001) | ||||
| Mitochondrial encephalomyopathy | 7587T > C | MT-CO2 | Met1Thr | 57 yr | 67 | <1 | 52 | 38, muscle | ↓ | (Clark et al. 1999) | |
| Proximal myopathy and lactic acidosis | 7671T > A | MT-CO2 | Met29Lys | 14 yr | 90 | 5 | 6, muscle | ↓ | (Rahman et al. 1999) | ||
| Multisystem mitochondrial disease | 7896G > A | MT-CO2 | Trp104X | 3 yr | 76 | 67 | 60 | 13, muscle | ↓ | (Campos et al. 2001) | |
| Multisystem mitochondrial disease | 7970G > T | MT-CO2 | E129X | 35 yr | 90 | 3, muscle | ↓ | (Horváth et al. 2005) | |||
| Myopathy, EXIT, lactic acidosis, lipidosis, ragged red fibers | 9379G > A | MT-CO3 | W58X | 14 yr | 93 | <1, hair | 1, muscle | ↓ | (Horvath et al. 2002) | ||
| MELAS | 9396G > A | MT-CO3 | Glu64Lys | 11 yr | 94 | 39 | 91 | 100, urinary sediment 74, saliva 77, fingernails 95, cybrids |
78, muscle 78, cybrids |
(Xu et al. 2021) | |
| MELAS | 9553G > A | MT-CO3 | Trp116X | 47 yr | 89 | 13, oral epithelium | 59, muscle | ↓ | (Wang et al. 2021) | ||
| Rhabdomyolysis | 9559delC | MT-CO3 | Frameshift | 27 yr | 58 | 38, musclec | ↓ | (Marotta et al. 2011) | |||
| EXIT, rhabdomyolysis | 9789T > C | MT-CO3 | Ser195Pro | 23 yr | 50 | <1 | <1, myoblasts | 10, muscle | ↓ | (Horváth et al. 2005) | |
| Mitochondrial encephalomyopathy | 9952G > A | MT-CO3 | Trp248X | 36 yr | 57 | 17, muscle | ↓ | (Hanna et al. 1998) | |||
| MELAS | 9957T > C | MT-CO3 | Phe251Leu | 7 yr | 81 | 60 | 79, muscle | Similar levels as referent | (Manfredi et al. 1995) | ||
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aAge of the patient at which the VAF and complex I activity were measured.
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bNormalized to protein.
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cNormalized to complex II activity.
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(AA) Amino acid; (VAF) variant allele frequency; (COX) cytochrome c oxidase; (EXIT) exercise intolerance; and (MELAS) mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.
