Table 1 Genomic and clinical features of the patients
From: Whole exome sequencing in Japanese spinocerebellar ataxia identifies novel variants
Patient number | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
Genomic features | |||||
 Gene | ELOVL4 | ELOVL4 | ELOVL5 | GRM1 | GRM1 |
 Chromosome | 6 | 6 | 6 | 6 | 6 |
 Position | 79921659 | 79919547 | 53291843 | 146434774 | 146398888 |
 Reference base | C | G | G | A | T |
 Alternative base | G | A | A | C | C |
 cytoBand | 6q14.1 | 6q14.1 | 6p12.1 | 6q24.3 | 6q24.3 |
 Exonic Function | Nonsynonimous | Nonsynonimous | Nonsynonimous | Nonsynonimous | Nonsynonimous |
 Amino Acid change | NM_022726 Exon 4 c.507 G > C p.W169C | NM_022726 Exon 5 c.542 C > T p.A181V | NM_001242828 Exon 3 c.179 C > T p.S60F | NM_001278064 Exon 8 c.3563 A > C p.K1188T | NM_001278064 Exon 7 c.1849T>C p.Y617H |
 AlphaMissense | Likely pathogenic (0.964) | Likely pathogenic (0.886) | Ambiguous (0.470) | Likely Benign (0.191) | Likely Benign (0.247) |
 CADD | 28.6 | 24.9 | 25.1 | 22.5 | 26.4 |
 SIFT (Sequence) | Deleterious (0.01) | Tolerated (0.13) | Deleterious (0.02) | Tolerated (1.00) | Tolerated (0.51) |
 PolyPhen-2 (HumVar) | Possibly damaging (0.600) | Benign (0.271) | Possibly damaging (0.869) | Benign (0.014) | Probably damaging (1.000) |
 MutationTaster | Deleterious | Deleterious | Deleterious | Benign | Benign |
 gnomAD Total | N/A | N/A | 0.000001239 | N/A | N/A |
 NCBN Total | N/A | N/A | N/A | N/A | N/A |
 ACMG criteria | Uncertain significance (PM1, PM2, PP3) | Uncertain significance (PM1, PM2) | Uncertain significance (PP3) | Uncertain significance (PM2, BP4) | Uncertain significance (PM2) |
Clinical features | |||||
 Sex | Female | Female | Male | Female | Male |
 The age at disease onset (years) | 24 | 26 | 37 | 65 | 57 |
 The age at last visit (years) | 36 | 47 | 55 | 77 | 83 |
 Family history | (-) | Mother, sibling, maternal uncle, maternal grandmother, and maternal cousins | Mother, sibling, maternal uncle, and maternal aunt | Mother and sibling | Mother |
 Time from disease onset to wheelchair use (years) | Walking independently | Cane-assisted gait | 16 | 12 | 12 |
 Eye movements | Saccadic | Saccadic | Saccadic and upgaze pulsy | Saccadic | Saccadic |
 Nystagmus | Horizontal | Gaze directional | Lateral gaze directional | (−) | (−) |
 Dysarthria | (+) | (+) | (+) | (+) | (+) |
 Limb ataxia | (+) | (+) | (+) | (+) | (+) |
 Trunkal ataxia | (+) | (+) | (+) | (+) | (−) |
 Spasticity | (+) | (−) | (−) | (−) | (+) |
 Deep tendon reflex | Increase | Decrease (Lower limbs) | Increase | Decrease | Increase (Lower limbs) |
 Extrapyramidal signs | (−) | Postual/Intentional tremor and rigidity | (−) | No-no head tremor | (−) |
 Sensory disturbances | (-) | (−) | (−) | (−) | (−) |
 Bladder and rectal disturbances | (−) | (−) | (+) | (−) | (+) |
 Cognitive decline | (−) | (−) | (−) | (+) | (−) |
 Skin changes | (+) | (−) | (−) | (−) | (−) |
Head imaging findings | |||||
 Brain stem atrophy | (+) | (+) | (+) | (+) | (−) |
 Cerebellar atrophy | (+) | (+) | (+) | (+) | (+) |
 White matter lesion | (−) | (−) | (−) | (+) | (−) |
 Other features | Hot cross bun sign | Calcification in the globus pallidus and dentate nucleus | N.P. | N.P. | N.P. |
