Table 1.
Clinical information and results from the CACNA1A mutational screening in episodic ataxia patients with identified variants.
| Patient | Age of onset (years) | Frequency of the episodes (per month) | Duration | Trigger(s) | MRI | Other features | Variant | Restriction enzyme | PhyloPc/PhastConsd scores | SIFT scoree | PolyPhen-2 scoref | Reference | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| cDNAa | Exon | Proteinb | Domain | ||||||||||||
| EP-004 | infancy | NA | NA | NA | NA | ACZ responsive, MO, learning disability, motor clumsiness | c.749delG | 5 | p.G250Efs*60 | DI, S5-S6 loop | +TaqI (mismatch) | 5.84/1 | — | — | — |
| 432B | 6 | >1 | 15′-3 h | stress, fatigue | normal | ACZ responsive | c.G959A | 6 | p.W320* | DI, S5-S6 loop | +AccI | 5.78/1 | — | — | — |
| A03_44 | NA | NA | NA | NA | NA | FHM, interictal ataxia, nystagmus | c.C1502T | 11 | p.T501Mg | DII, S1 | +FatI | 4.32/1 | Damaging (0.00) | Probably damaging (1.00) | 24 |
| A98_279 | 58 | ∼30 | 30′-1 h | NA | normal | episodic hand dystonia | c.G1913A | 14 | p.G638D | DII, S5-S6 loop | −AciI | 5.63/1 | Damaging (0.03) | Probably damaging (1.00) | 4 |
| 7A806 | 5 | 4 | NA | NA | NA | MO | c.2042-43delAG | 16 | p.Q681Rfs*100 | DII, S5-S6 loop | -DdeI | — | — | — | 21–24 |
| 474 | 8 | 1–4 | 3–6 h | NA | deep WM hyperinte-nsities | worsen on CBZ and PHT, ACZ responsive | c.5253-2259_5403+ 1135del | 35 | p.S1753Cfs*2 | DIV, S5-S6 loop | — | — | — | — | — |
| 335a | <1 | NA | 48 h | NA | normal | migraine, visual aura | c.T5547A | 37 | p.Y1849* | Cytoplasmic tail | −PsiI | 4.33/1 | — | — | — |
| 340 | 4 | NA | NA | exercise, fatigue, emotional stress | temporal arachnoidal cyst | congenital squint, nystagmus, ACZ responsive | c.C5569T | 37 | p.R1857* | Cytoplasmic tail | +BspHI (mismatch) | 3.33/1 | — | — | 20 |
| 389A | 2 | 8–12 | 6–8 h upon sleep | stress, exercise, coffee, tea | mild cerebellar atrophy | improves on ACZ, MO, interictal ataxia, nystagmus | c.C5569T | 37 | p.R1857* | Cytoplasmic tail | +BspHI (mismatch) | 3.33/1 | — | — | 20 |
| 349A | 1.5 | 1–2 | 30′ | stress | normal | nystagmus | c.C6665T | 46 | p.P2222Lg | Cytoplasmic tail | −FauI | 2.83/1 | Tolerated (1.00) | Benign (0.06) | — |
MRI: Magnetic Resonance Imaging; NA: not available; ACZ: acetazolamide; MO: migraine without aura; FHM: Familial Hemiplegic Migraine; WM: white matter; CBZ: carbamazepine,; PHT: phenytoin; D: domain; S: segment. aReference sequence for cDNA nomenclature: NM_001127221 (nucleotide c.279A corresponding to the initiation codon, ATG). bRererence sequence for protein nomenclature: NP_001120693. cPhyloP score: Positive scores indicate sites that are predicted to be conserved, whereas negative scores indicate sites predicted to be fast-evolving. dPhastCons score: It ranges from 0 (non conserved amino acid positions) to 1 (highly conserved amino acid positions). eSIFT score: It ranges from 0 to 1. The amino acid substitution is predicted as damaging if the score is <=0.05, and tolerated if the score is >0.05. fPolyPhen-2 score: It ranges from 0 to 1. The aminoacid substitution is predicted as probably damaging if the score is >0.85, possibly damaging (score is between 0.15 and 0.85) or benign (score < 0.15). gVariants p.T501M and p.P2222L have the rs codes rs121908240 and rs778551911, respectively.