Table 3.
Examples of genetic alterations of isolated MRC Complex I to V deficiency with a predominant muscular involvement phenotype (or isolated mitochondrial myopathy).
| Genes | Type of Article | Type of Mutation | Patients N/Age at the Time of the Examination | Clinical Presentation | References |
|---|---|---|---|---|---|
| MT-ND1 | CR | m.4087A>G (pThr261Ala) in homoplasmy | 1 pt/41 yo | Ptosis, ophthalmoparesis, weakness, rabdomyolisis after suxamethonium injection | [31] |
| MT-ND1 | CR | m.3365T>C (pLeu20Pro) | F/28 yo | Exercise intolerance, fatigue, weakness. Metabolic acidosis, high serum lactate concentration | [32] |
| MT-ND1 | CR | m.4175G>A (pTrp290 *) | NA/22 yo | Exercise intolerance, exertion-related muscle weakness and pain. Ptosis. High serum lactate concentration |
[32] |
| MT-ND1 | CR | m.3902_3908invACCTTGC | M/43 yo | Exercise intolerance and myalgia. Weakness. | [36] |
| MT-ND2 | CR | m.4831G>A (pGly121Asp) | M/21 yo | Fatigability, muscle weakness. High serum lactate concentration. | [33] |
| MT-ND2 | CR | m.5133_5134del | M/28 yo | Exercise intolerance. High serum lactate concentration | [20] |
| MT-ND4 | CR | m.11832G>A (pTrp358 *) | M/38 yo | Exercise intolerance, fatigue, myalgia. | [34] |
| MT-ND5 | CR | m.13271T>C (p. Leu312Pro) | F/27 yo | Exercise intolerance. High serum lactate concentration. | [35] |
| MT-ND6 | CR | m.14512_14513del p.(Met54Serfs *7) |
M/27 yo | Exercise intolerance, muscle weakness, ptosis, intermittent diplopia. | [38] |
| TMEM126B | CR | c.635G>T (p.Gly212Val) and c.401delA (pAsn134Ilefs *2) |
2F and 4M/ 21–36 yo |
Exercise intolerance, muscle weakness. High serum lactate concentration | [39] |
| TMEM126B | CR | c.635G>T (p.Gly212Val) and c.397G>A (p.Asp133Asn) (2/3); c.635G>T (pGly212Val) and c.208C>T (p.Gln70 *) |
1F and 2M/ 22–38 yo |
Proximal muscle weakness. Exercise induced myalgia. High serum lactate concentration | [40] |
| ACAD9 | CS | 42 missense mutations, | 41F and 29M/22 days—44 yo | Exercise intolerance, muscle weakness, cardiomyopathy. Metabolic acidosis. High serum lactate concentration | [41] |
| 1 frame shift, 1 nonsense, | |||||
| 7 splice sites and 1 initiation codon | |||||
| MT-CYB | CR | m.15084G>A (pTrp113 *); | 2F and 3M/ 32—52 yo |
Exercise intolerance, muscle weakness. High serum lactate concentration. Exercise-induced myoglobinuria. | [34] |
| m.15168G>A (pTrp141 *); | |||||
| m.15723G>A (pTrp326 *); | |||||
| m.14846G>A (pGly34Ser); | |||||
| m.15498_15521del | |||||
| MT-CYB | CR | m.15615G>A (pGly290Asp) | M/29 yo | Exercise intolerance | [42] |
| MT-CYB | CR | m.15242G>A (pGly166 *) | F/34 yo | Exercise intolerance. High serum lactate concentration; encephalopathy with seizures and hallucinations. | [43] |
| MT-CYB | CR | m.1517G>A (pGly142 *) | F/40 yo | Exercise intolerance, muscle weakness, fatigue and myalgia | [44] |
| MT-CYB | CR | m.15800C>T (pGln352 *) | F/24 yo | Exercise intolerance, fatigue. | [45] |
| MT-CO1 | CR | m.6708G>A (predicting the loss of the last 245 amino acids of 514 in COX II) | F/30 yo | Exercise intolerance. Muscle weakness and fatigue, myalgia. Exercise-induced myoglobinuria. | [46] |
| MT-CO2 | CR | m7671T>A p(Met29Lys) | M/14 yo | Muscle weakness and fatigue. High serum lactate concentration. | [47] |
| MT-CO2 | CR | m8088delT (pLeu168 *) | F/16 yo | Exercise intolerance, muscle weakness. High serum lactate concentration. Anemia | [48] |
| MT-CO3 | CR | m9379G>A (pTrp58 *) | M/20 yo | Exercise intolerance. Muscle weakness, hypotonia and scapular winging; The symptoms spontaneously regressed through the years. |
[49] |
| COX6A2 | CR | c.117C>A (p.Ser39Arg) and c.127T>C (p.Cys43Arg) | M/9 yo | Muscle weakness, hypotonia, facial weakness, high arched palate since infancy | [50] |
| COX10 | CR | c.1007A>T (p.Asp336Val) and c.1015C>T (p.Arg339Trp) |
F/37 yo | Failure to thrive. Exercise intolerance, muscle weakness and fatigue, renal Fanconi syndrome. Metabolic acidosis. | [51] |
F: female; M: male; NA: not available yo: years old; * truncation; CR: case report; CS: cohort study. All the mtDNA mutations were heteroplasmic except for one (Rafiq J et al., 2015).