Table 1.
List of known causative genes and variants of mitochondrial cardiomyopathy (MCMs).
| a. Gene Mutations in Mitochondrial DNA and Mitochondrial Disorder | |||
|---|---|---|---|
| Genes | Amino Acid Change | Cardiological Phenotype | Other Disorder |
| MT-ND1: m. 3481G > A | p. Glu59Lys | HCM, LVNC | LHON |
| MT-ND4: m. 11778G > A | p. Arg340His | DCM | LHON, progressive dystonia |
| MTND5: m. 12338T > C | p. Met1Thr | HCM. WPW | Leigh syndrome |
| MT-ATP6/8: m. 8528 T > C | p. Pro10Ser | HCM | Subacute encephalopathy |
| MT-ATP6: m. 8851 T > C | p. Trp109Arg | HCM | NARP, Leigh disease |
| MT-ND6: m. 14453G > A | p. tRNALeu | HCM | LHON, MELAS |
| MT-ND6: m. 8528 T > C | Syn | DCM | LHON, MELAS |
| MT-CYB: m. 14849T > C | p. Ser35Pro | HCM | Septo-optic dysplasia |
| MT-TL1: m. 3260A > G | p. tRNALeu (UUR) | HCM, RCM, LVNC | MELAS, Leigh syndrome |
| MT-TI: m. 4300A > G | - | HCM, DCM | MERRF, Leigh syndrome |
| MT-TV: m. 1644G > A | - | HCM | MERRF, Leigh syndrome |
| MT-TK: m. 8344A > G | p. tRNALys | HCM | MERRF, Leigh syndrome |
| MT-RNR1: m. 1555A > G | - | RCM | Maternally inherited deafness |
| b. Genes Mutations in Nuclear DNA and Mitochondrial Disorder | |||
| Genes | Amino acid change | Cardiological phenotype | Other disorder |
| NDUFS2: c. 208 + 5G > A | p. Pro229Gln | HCM | Mitochondrial CI deficiency |
| NDUFV2: c. 669_670insG | p. Ser224fs | HCM | Mitochondrial CI deficiency |
| NDUFA11: c. 99 C + 5G> A | p. Ala132Pro | HCM | Mitochondrial CI deficiency and/or encephalocardiomyopathy |
| NDUFB11: c. 136_142dup | p. Arg134Ser | LVNC, WPW | Mitochondrial CI deficiency |
| SDHD: c. 275A > G | p. Asp92Gly | DCM, LVNC | Mitochondrial CII deficiency |
| NDUFAF1: c. 631C > T | p. Arg211Cys | HCM | Mitochondrial CI deficiency |
| ACAD9: c. 797G > A | p. Arg266Gln | HCM | Mitochondrial CI deficiency |
| SCO2: c. 418G > A | p. Glu140Lys | HCM | Cytochrome C oxidase deficiency |
| COX10: c. 610A > G | p. Asn204Asp | HCM | Mitochondrial CIV deficiency |
| COX15: c. 1129A > T | p. Lys377x | HCM | Cytochrome C oxidase deficiency |
| COA6: c. 196 T > C | p. Trp66Arg | HCM | Mitochondrial CIV deficiency |
| COX6B1: c. 58C > T | p. Arg20Cys | HCM | MELAS, MERRF |
| TEME70: c. 366A > T | p. Tyr112Ter | HCM | Mitochondrial CV deficiency |
| TEME70: c. 317-2A > G | - | HCM | Mitochondrial CV deficiency |
| AARS2: c. 1774C > T | p. Arg958 * | HCM | COXPD 8 |
| MRPS22: c. 644T > C | p. Leu215Pro | HCM | COXPD 8 |
| MRPL3: c. 950C > G | p. Pro317Arg | HCM | COXPD9 |
| MRPL3: c. 49delC | Arg17Aspfs * 57 | HCM | COXPD9 |
| MRPL44: c. 467T > G | p. Leu156Arg | HCM | Mitochondrial CIV deficiency |
| TSFM: c. 355G > C | p. Val119Leu | HCM, DCM | COXPD 3 |
| GTPB3: c. 1291dupC; | p. Pro430Argfs * 86 | HCM, DCM | COXPD23, Encephalopathy |
| GTPB3: c. 1375G > A | p. Glu459Lys | HCM, DCM | COXPD23 |
| GTPB3: c. 476A > T | p. Glu159Val | HCM, DCM | lactic acidosis, leukodystrophy |
| GTPB3: c. 964G > C | p. Ala322Pro | HCM, DCM | lactic acidosis, leukodystrophy |
| MTO1: c. 1282G > A | p. Ala428Thr | HCM | COXPD10 |
| MTO1: c. 1858dup | p. Arg620Lysfs * 8 | HCM | COXPD10 |
| ELAC2: c. 631C > T | p. Arg211 * | HCM | COXPD17 |
| ELAC2: c. 1559C > T | p. Thr520Ile | HCM | COXPD17 |
| ELAC2: c. 460T > C | p. Phe154Leu | MELAS | Cardiac failure |
| ELAC2: c. 1267C > T | p. Leu423Phe | DCM | Cardiac failure, COX deficiency |
| TAZ: c. 527A > G | p. His176Arg | DCM, LVNC | BTHS |
| AGK: c. 306T > G | p. Tyr102Ter | HCM | Sengers syndrome |
| SLC22A5: c. 12C > G | p. Tyr4 * | HCM, DCM | Systemic primary carnitine deficiency |
| ACADVL: c. 104delC | p. P35Lfs * 26 | HCM, DCM | VLCAD deficiency |
| ACADVL: c. 848T > C | p. V283A | HCM | VLCAD deficiency |
| ACADVL: c. 1141_1143del GAG | p. E381del | HCM | VLCAD deficiency |
| ACAD9: c. 555-2A > G | p. Ala390Thr | HCM | MTP deficiency with myopathy and neuropathy |
| ATAD3A-C: c. 1064G > A | p. G355D | HCM | Hereditary spastic paraplegia, axonal neuropathy |
| SLC25A4: c. 239G > A | p. Arg80His | HCM | Mitochondrial DNA depletion syndrome-12 |
| SLC25A4: c. 703C > G | p. Arg235Gly | HCM | Mitochondrial DNA depletion syndrome-12 |
| QRSL1: c. 398G > T | p. G133V | HCM | COXPD40 |
| KARS: c. 1343 T > A: | p. V448D | HCM, DCM, MC | Infantile-onset progressive leukoencephalopathy /or deafness |
| KARS: c. 953 T > C | p. I318T | HCM, DCM, MC | Mitochondrial cytopathy |
| TOP3A: c. 298A > G | p. Met100Val | DCM | adult-onset mitochondrial disorder |
| TOP3: c. 403C > T | p. Arg135Ter | DCM | Adult-onset mitochondrial disorder |
| FXN: GAA repeat expansion | - | HCM | Friedreich ataxia, MELAS, MERRF |
| BOLA3: c. 287A > G | p. H96R | HCM | Multiple mitochondrial dysfunctions syndrome-2 with hyperglycinemia |
| CoQ4: c. 718C > T | p. R240C | HCM | Coenzyme Q10 deficiency 7 |
| CoQ4: c. 421C > T | p. R141X | HCM | Lethal infantile mitochondrial disorder |
| DNAJC19: IVS3-1G > C | - | DCM, LVNC | 3-methylglutaconic aciduria type V |
Abbreviations: BTHS, Barth syndrome; COXPD, combined oxidative phosphorylation deficiency; COX, cyclooxyganese; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LHON, Leber’s hereditary optic neuropathy; LVNC, left ventricular non compaction; MC, mitochondrial myopathy; MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; MERRF, myoclonus epilepsy associated with ragged red fibers; MTP, mitochondrial trifunctional protein; RCM, restrictive cardiomyopathy; NARP, neurogenic muscle weakness, ataxia, and retinitis pigmentosa; VLCAD, very long-chain acyl-CoA dehydrogenase; WPW, Wolff–Parkinson–White syndrome. “-” mean noncoding. The asterisk denotes the position of the termination codon. The number represents its position in the protein, i.e., 19 means it is in the 19th position from the N terminal to the C terminal.