Variant | Zygosity | Cases/Families | Diagnosis, clinical features | Age of onset | Functional studies | Gain/loss of function | References |
---|---|---|---|---|---|---|---|
p.Asn71Tyr c.211A > T | HT | 1 Taiwanese family | CMT2 a Slowly progressing sensorimotor LE and UE neuropathy NCV: intermediateb | 11-45y | Not localized in cytoplasm but in organelles, formation of aggregates, growth inhibition, aminoacylation severely defective | ||
p.Lys81Thr c.242A > C | compound HTc | 2 mixed-European descent siblings | Microcephaly, epileptic encephalopathy with persistent myelination defect | Congenital, 3mo | Aminoacylation mildly defective, reduced yeast cell survival | LoF | [31] |
p.Gly102Arg c304G > C | HT | 1 North American family | Mild axonal neuropathy with hyperreflexia indicating superimposed myelopathy NCV: Normal or slight decrease | Third to fifth decade of life | No yeast cell growth | LoF | [24] |
p.Arg326Trp c.976GC > T | HT | 1 Dutch family | CMT2N Severe motor (sensorimotor) LE polyneuropathy with axonal and demyelinating, or pure axonal features NCV: intermediate or normal | First to third decade of life | No yeast cell growth, toxicity in zebrafish embryos, with aberrant morphology and neurologic phenotype | LoF | [41] |
p.Arg329His c.986G > A | HT | 2 French families | CMT2 Sensorimotor LE or LE and UE axonal neuropathy, NCV: slight to moderate decrease | 6-54y | LoF | [14] | |
1 Australian family | CMT2N Axonal sensorimotor neuropathy and variable sensorineural deafness NCV: intermediate | Early onset | Aminoacylation severely defective | [23] | |||
5 British families | CMT2 sensorimotor poly- or LE neuropathy NCV: intermediate | Congenital to 30y | [5] | ||||
p.Glu337Lys c.1009G > A | HT | 1 family | CMT2 Severe sensorimotor polyneuropathy with axonal and demyelinating features NCV: moderate decrease | First to third decade of life | Increased yeast growth, increased aminoacylation efficiency, toxicity in zebrafish embryos, with aberrant morphology and neurologic phenotype | GoF | [41] |
p.Ser627Leu c.1880C > T | HT | 1 family | CMT2N Severe axonal sensorimotor LE and UE neuropathy, predominantly distal NCV: intermediate | Third decade of life | Reduced yeast viability; toxicity in zebrafish embryos, with aberrant morphology and neurologic phenotype | LoF | [41] |
p.Glu688Gly c.2063A > G | HT | 1 British family | CMT2 pedigree with transitional forms to CMT1 sensorimotor poly- or LE neuropathy; split hand deformity NCV: intermediate | Congenital to first decade of life | [5] | ||
p.Tyr690Leufs*3 c.2067dupC | compound HTd | 2 mixed-European descent sisters | Progressive microcephaly, MRI shows hypomyelination; epileptic encephalopathy; spastic paraplegia | Congenital | Reduced protein expression, reduced aminoacylation activity, reduced editing activity, accumulation of [3H]Ser-tRNA Ala | LoF | [25] |
p.Arg751Gly c.2251A > G | compound HTc, HM | 1 mixed-European descent individual | Microcephaly, epileptic encephalopathy with persistent myelination defect | Congenital, 3mo | Aminoacylation severely defective, normal editing activity, normal yeast survival | LoF | [27] |
p.Glu778Ala c.2333A > C | HT | 1 Australian family | Possible CMT2N Rippling muscles, cramps, and polyneuropathy; or only rippling muscles and cramps NCV: severe axonal lesions | N.A. | Normal yeast growth, normal localization, normal aminoacylation, normal editing activity. | [23] | |
p.Asp893Asn | HT | 1 Chinese family | Distal hereditary motor neuropathy (dHMN) Mild UE weakness, slow progression, no sensibility disturbance. Normal NCV, but EMG with neurogenic lesion | First to sixth decade of life | [42] | ||
p.Gly913Asp c.2738G > A | compound HTd | 2 mixed-European descent sisters | Progressive microcephaly, hypomyelination, epileptic encephalopathy, spastic paraplegia | Congenital | Reduced protein expression, reduced aminoacylation activity, normal editing activity | [25] |