Table 1.
Clinical and electrophysiological characteristics of CMT2A patients bearing mutation within MFN2 GTPase domain.
| Nucleotide change | Protein change | Clinical details | Phenotype | Score | References | |||
|---|---|---|---|---|---|---|---|---|
| Age of onset (years) | CMAP (median nerve) [mV] | CMTNS/FDS | Peripheral neuropathy | CNS/cranial nerves | ||||
| c.311 G > A | p.Arg104Gln | — | — | −/− | healthy individual with normal results of electrophysiological examination | — | 0 | 27 |
| c.310 C > T | p.Arg104Trp | 1–10 | 0.0, 0.1, 0.8, 1.6; 1.8, 2,7 | 22/726 | early onset CMT2A (1.5) or classical CMT2A (1) |
pyramidal signs (2) optic atrophy (1) mental retardation (1) other minor symptoms (0.5) |
5.5–6 | 15, 25, 26, 28– 30 |
| c.380 G > A | p.Gly127Asp | 16 | 11.9 | 4/2 | classical CMT2A (1) | extensor plantar responses (2) | 3 | 2 |
| c.380 G > T | p.Gly127Val | 6–62 | 0.8, 2.0, 8.4 | −/− | late onset CMT2A (0.5) or classical CMT2A (1) |
— | 0.5–1 | 35 |
| c.494 A > G | p.His165Arg | 6–16 | 1.0, 5.2, 11.5, 20.1 | 5/1 | classical CMT2A (1) | subcortical lesions in MRI (0.5) sensorineural hearing loss (0.5) |
2 | 2, 3, 22 |
| c.493 C > G | p.His165Asp | 4–20 | 5.0, 5.0, 7.0, 11.0 | −/− | classical CMT2A (1) or early onset CMT2A (1.5) |
pyramidal signs (2) | 3–3.5 | 21, 24 |
| c.494 A > T | p.His165Leu + ALS | 14 | 2.2 | −/− | classical CMT2A (1) ALS is rather casual and not associated with MFN2 mutation |
— | 1 | 23 |
| c.493 C > T | p.His165Tyr | 12 | — | −/− | classical CMT2A (1) | — | 1 | 3 |
| c.629 A > T | p.Asp210Val | 1.5 | — | −/− | early onset CMT2A (1.5) | pyramidal signs (2) cerebellar ataxia (0.5) deafness (0.5) optic atrophy (1) cataracts (0.5) learning difficulties (0.5) mitochondrial myopathy (0.5) |
7 | 12 |
| c.628 G > T | p.Asp210Tyr | 0.5 | no values | −/− | early onset CMT2A (1.5) | pyramidal signs (2) microcephaly (0.5) tremor (0.5) sensorineural hearing loss (0.5) optic atrophy (1) developmental delay (1) |
7 | 36 |
| c.730 G > C | p.Val244Leu | 4 | 6.3 | −/− | early onset CMT2A (1.5) | periventricular leukomalacia (0.5) | 2 | 40 |
| c.730 G > A | p.Val244Met | <5 | — | −/− | early onset CMT2A (1.5) | — | 1.5 | 15, 39 |
| c.749 G > A | p.Arg250Gln | 12–21 | — | −/− | late onset CMT2A (0.5) or classical CMT2A (1) |
— | 0.5–1 | 3, 37 |
| c.748 C > T | p.Arg250Trp + Arg400* + Arg476* | 4–10 | 2.7 | −/− | classical CMT2A (1) or early onset CMT2A (1.5) |
— | 1–1.5 | 3, 38 |
| c.751 C > G | p.Pro251Ala | 8–50 | — | −/− | classical CMT2A (1) tremor (0.5) |
— | 1.5 | 31 |
| c.752 C > G | p.Pro251Arg | 1, 2 | — | 11–20/− | early onset CMT2A (1.5) wheelchair (1) | — | 2.5 | 37, 41 |
| c.752 C > T | p.Pro251Leu | 25 | — | 13/2 | late onset CMT2A (0.5) | — | 0.5 | 42 |
| c.775 C > T | p.Arg259Cys | >30 | decreased | −/− | late onset (0.5) | sudden visual loss (1.5) | 2 | 17 |
| c.776 G > T | p.Arg259Leu | 19 | — | −/− | classical CMT2A (1) | mild pyramidal signs (1.5) | 2.5 | 18 |
| c.776 G > C | p.Arg259His | 17 | — | 10/2 | classical CMT2A (1) | — | 1 | 19 |
| c.821 G > A | p.Arg274Gln | 11–35 | — | −/− | classical CMT2A (1) | — | 1 | 31 |
| c.820 C > T | p.Arg274Trp | 10 | — | −/− | classical CMT2A (1) | markedly reduced nerve conduction velocity in the motor fibers of the median nerve (0.5) proximal weakness (0.5) mental retardation (1) |
3 | 1 |
| c.827 A > G | p.Gln276Arg | 10 | — | −/− | classical CMT2A (1) | optic nerve atrophy (1) | 2 | 32 |
| c.828 G > C | p.Gln276His | 9 | decreased | −/− | classical CMT2A (1) | optic nerve atrophy (1) | 2 | 33 |
| c.830 A > G | p.His277Arg | <15 | — | −/− | classical CMT2A (1) | — | 1 | 3 |
| c.829 C > T | p.His277Tyr | <10 | — | −/− | classical CMT2A (1) | pyramidal signs (2) vasomotor troubles (0.5) |
3.5 | 15 |
Legend: “-“ the results of the analysis were not reported, “−/−“ nor CMTNS, neither FDS score was reported, CMTNS-Charcot Marie Tooth Neuropathy scale, FDS- Functional disability scale, CMAP- compound muscle amplitude potential, CNS-central nervous system.