From: A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation
Genomic position | Nucleotide change | Amino acid change | Exon | Type | RefSNP | gnomAD MAF | SCA35 carriers | TG6 activity (functional studies) | Clinical features | Mean age at onset (years) | Study reference | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
20:2398091 | c.1550T>G | p.L517W | 10 | Missense | rs387907097 | 0.0001 | 9 | Reduced (in vitro) | Gait ataxia Spasmodic torticollis Cerebellar dysarthria Intentional tremor Dysmetria Pyramidal signs (hyperreflexia, Babinski sign) | 44 | [2] | |
20:2381081 | c.980A>G | p.D327G | 7 | Missense | rs387907098 | 9.6 × 10−5 | 2 | Reduced (in vitro) | Gait ataxia Cerebellar dysarthria Intentional tremor Eye movements disturbances (slowness) | 41 | [2] | |
20:2398069 | c.1528G>C | p.D510H | 10 | Missense | rs201964784 | 0.0001 | 5 | Reduced (in vitro) | Gait ataxia Dysmetria Pyramidal signs (hyperreflexia, Babinski sign) Postural and intentional tremor Delayed speech development Mental retardation Cognitive impairment Cerebellar dysarthria Numbness in the extremities Eye movements disturbances (limited extraocular movements, dysmetric saccades) Impaired proprioception | 20 | ||
20:2375989 | c.331C>T | p.R111C | 3 | Missense | rs372250159 | 2.5 × 10−5 | 2 | Reduced (in vitro and in vivo) | Gait ataxia Limb ataxia Cerebellar dysarthria Tremor Eye movements disturbances (saccade/pursuit aberrations) Pyramidal signs (hyperreflexia) | 23 | [3] | |
20:2411135_2411137 | c.1722_1724delAGA | p.E574del | 11 | Deletion | NA | 4.0 × 10− 6 | 1 | Reduced (in vitro) | Gait ataxia Cerebellar dysarthria Limb ataxia Tremor Nystagmus Eye movements disturbances (saccade/pursuit aberrations) Pyramidal signs (hyperreflexia) | 56 | [3] | |
20:2377270 | c.543G>T | p.Q181H | 4 | Missense | NA | NA | 1 | Reduced (in vitro) | Gait ataxia Myoclonus Epilepsy | 19 | [8] | |
20:2384304 | c.1171G>A | p.V391M | 9 | Missense | rs116904482 | 0.0008 | 1 | Reduced (in vitro) | Gait ataxia Extrapyramidal signs Dystonia | 36 | [8] | |
20:2384455 | c.1322A>G | p.Y441C | 9 | Missense | rs138950659 | 1.2 × 10−5 | 1 | Reduced (in vitro) | Gait ataxia Pyramidal signs (spasticity) Cerebellar dysarthria Dysphagia | 54 | [8] | |
20:2397883 | c.1342C>T | p.R448W | 9 | Missense | rs147979536 | 0.015 | 1 | Not reduced (in vitro) | Gait ataxia | 20 | [8] | |
20:2398046 | c.1505T>A | p.L502Q | 10 | Missense | NA | 7.1 × 10−6 | 1 | Not reduced (in vitro) | Ataxia | > 50 | [8] | |
20:2411658_2411660 | c.1951_1952insAAC | p.Q652dup | 12 | Duplication | NA | 0.0013 | 1 | Not reduced (in vitro) | Gait ataxia Myoclonus | NA | [8] | |
20:2375947 | c.288_290delC | p.L97* | 3 | Frameshift | NA | 1.1 × 10−4 | 1 | NA | Postural and intentional tremor Cerebellar dysarthria Dystonia Dysmetria Gait ataxia Pyramidal signs (hyperreflexia, Babinski sign) | 35 | [10] | |
20:2361622 | c.7+1G>T | Splice site change | 1 | Splicing | NA | 1.4 × 10− 4 | 2 | NA | Gait ataxia Cerebellar dysarthria Tremor | 57 | [5] | |
20:2398019 | c.1478C>T | p.P493L | 10 | Missense | NA | 8.0 × 10− 5 | 1 | NA | Gait ataxia Cerebellar dysarthria Tremor Cognitive impairment | 60 | [5] | |
20:2380376 | c.841delC | p.L281* | 6 | Frameshift | NA | NA | 1 | NA | Gait ataxia Cerebellar dysarthria Extrapyramidal signs Dysmetria Pyramidal signs (hyperreflexia) | 40 | [9] | |
20:2384077 | c.1024C>T | p.R342W | 8 | Missense | rs150566697 | 0.0002 | 1 | Reduced (in vitro) | Gait ataxia Cerebellar dysarthria Eye movements disturbances (ocular dysmetria, slow saccades) Pyramidal signs (hyperreflexia, Babinski sign, ankle clonus) | 54 | Current study |