EPM_CSNK1E
- Gene
- CSNK1E
- Disease
- EPM
- Inheritance
- AR
- Classification
- Moderate
- Total Score
- 8
- Publications Reviewed
- 3
- Publication Span
- 6.67 years
- Last Updated
- 03/09/2025
- Curator(s)
- Macayla Weiner
Description
A heterozygous CGG repeat expansion in exon 1/5'UTR of CSNK1E at the FRA22A locus was reported in one Azerbaijani proband with progressive myoclonic epilepsy, ataxia, cognitive decline, and early death after exome and long-read analyses excluded other plausible causes. The expanded allele showed increased methylation, and prior FRA22A work demonstrated CSNK1E methylation and reduced expression in a CGG-expansion carrier. Unaffected relatives carried expanded or intermediate alleles, supporting incomplete penetrance and the need for careful interpretation of inheritance and penetrance.
Genetic evidence
Total: 5.5
| Singular Evidence | Probands | PMID:40751262 | 1.5 | One Azerbaijani EPM proband with onset at 10 years carried a heterozygous CSNK1E CGG expansion in exon 1/5'UTR (longest allele CGG n=745) after exome and long-read analyses found no other plausible EPM-related variant; functional methylation data were reported. Expansion was also present in an unaffected sibling, consistent with incomplete penetrance. |
| Statistics | Case-control data | PMID:40751262 | 4 | Population comparison using 908 1KGP ONT genomes found no comparable large CSNK1E CGG expansions; 98.7% had <20 repeats and the longest observed alleles were CGG n=48 and n=47, versus CGG n=745 in the proband and n=980 in an unaffected sibling. Matching and penetrance limitations remain. |
Experimental evidence
Total: 2.5
| Function | Regulatory impact | PMID:30488659 | 1 | A de novo CSNK1E splice-site SNV in West syndrome epileptic encephalopathies with RT-PCR evidence of abnormal splicing and gene-level brain/coexpression analyses. This evidence supports a regulatory impact of CSNK1E variants in an individual with epileptic encephalopathy but is not specific to the CGG expansion. |
| Functional Alteration | Patient cells | PMID:32937144 | 1 | CSNK1E CGG expansion, methylation, and reduced expression was observed in a FRA22A carrier. Phenotypic data was not provided, therefore this provides support for the regulatory impact of the specific expansion but is not EPM-specific. |
| Functional Alteration | Non-patient cells | PMID:32937144 | 0.5 | Non-patient/control comparison in the FRA22A study showed control samples were unmethylated at the CSNK1E CGG region; the population methylation screen also identified six individuals with gain of methylation overlapping the CSNK1E 5'UTR CGG repeat. Evidence is locus-specific but not EPM-specific. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.