Table 2.
Different frequencies of the cardinal phenotypic features related to CACNA1E in terms of the location of the pathogenic variant along the protein domain
| Location of the variant (protein level) | Missense variant | Severe developmental delay |
Refractory epilepsy |
Contractures |
Movement disorder (dystonia or choreoathetoid movements) |
Macrocephaly |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Present | Absent | Present | Absent | Present | Absent | Present | Absent | Present | Absent | |||
| DI from p90 to p.350 | Tr. S5 | c.683T>C; p.(Leu228Pro) | 2 | 0 | 2 | 0 | 0 | 2 | 1 | 1 | 0 | 2 |
| Tr. S6 | c.1042G>C; p.(Gly348Arg) | |||||||||||
| Cytoplasmic topological domain between DI and DII from p.351 to p.476 | c.1054G>A; p.(Gly352Arg) | 11 | 0 | 11 | 0 | 7 | 4 | 11** | 0 | 5 | 5 | |
| DII from p.477 to p.703 | Cat. S4-S5 | c.1807A>C; p.(Ile603Leu) | 14 | 0 | 11 | 2 | 6 | 7 | 3 | 11** | 6 | 7 |
| Tr. S6 | c.2069G>A; p.(Gly690Asp) | |||||||||||
| c.2093T>C; p.(Phe698Ser) | ||||||||||||
| c.2098G>A; p.(Ala700Thr) | ||||||||||||
| c.2101A>G; p.(Ile701Val) | ||||||||||||
| c.2104G>A; p.(Ala702Thr) | ||||||||||||
| c.2104G>C; p.(Ala702Pro) | ||||||||||||
| Cytoplasmic topological domain between Dili and DIV from p.1423 to p. 1479 | c.4264A7gt;T; p.(Ile1422Phe) | 2 | 2** | 3 | 1 | 2 | 2 | 0 | 4 | 1 | 3 | |
| c.4274C>A; p.(Thr1425Asn) | ||||||||||||
| c.4288G>A; p.(Gly1430Arg) | ||||||||||||
| DIV from p. 1480 to p. 1724 | Tr. S6 | c.5159C>G; p.(Ala1720Gly) | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 |
| % | 93 | 7 | 90 | 10 | 52 | 48 | 43 | 57 | 40 | 60 | ||
**
p<0.05 (Fisher's test) in patients with variants in that protein domain compared to the rest of the patients. NA, not available.; Cyt, cytoplasmatic domain; Tr, transmembrane. Protein sequence based on entry Q15878 from Uniprot [The UniProt Consortium, 2018].