Locus EPM CSNK1E

Progressive myoclonic epilepsy is a heterogeneous neurodegenerative disorder characterized by early-onset myoclonus, epilepsy, generalized tonic-clonic seizures, and progressive neurological deterioration¹. It has also been proposed that this locus is also associated with developmental and epileptic encephalopathies². We hypothesize that the two diseases may make up an expressivity or phenotypic spectrum and/or that hypermethylation causes changes in onset and severity.

Prevalence

EPM found in one Azerbaijani proband¹and DEE found in two additional patients². This expansion has been reported in unaffected individuals¹.

Age of Onset

EPM case reports age of onset 10 years¹and DEE cases onset in infancy

HPO Terms

HP:0001336 Myoclonous HP:0001251 Ataxia HP:0002080 Intention Tremor HP:0007000 Morning Myoclonic Jerks HP:0001260 Dysarthia HP:0001249 Intellectual Disability HP:0002392 EEG with Polyspike Wave Complexes HP:0002070 Limb Ataxia HP:0000726 Dementia HP:0000992 Cutaneous Photosensitivity

Association

Mendelian

Locus

hg19 chr22:38713287-38713380

hg38 chr22:38317282-38317375

t2t chr22:38781587-38781680

Details

CGG repeat in exon 1 of CSNK1E. Longest reported expanded allele of an affected individual is 745, with an unaffected sibling with repeat length 980. Father had a repeat of 8 and mother of 131.

Mechanism

Unknown

Mechanism of this disease is largely unknown, but hypermethylation is observed. Expanded alleles exhibit hypermethylation and may mediate epigenetic silencing. Unaffected carriers have been observed, indicating variable expressivity or penetrance.

Detection

Exome sequencing does not reliably detect expansions at this locus. Reported cases were identified through methylation outlier detection and confirmed by targeted long-read sequencing [@pmid:40751262].

Year

2025

Location in Gene

Exon 1

Gene Strand

Alleles

Ref. Motif

CCG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CCG

Pathogenic (gene)

CGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

References

Direct supporting references for info on this page.

A CGG Repeat Expansion in CSNK1E Associated with Progressive Myoclonic Epilepsy with Incomplete Penetrance.

Fulya,Akçimen, Pilar,Alvarez Jerez, Ulviyya,Guliyeva, Jasmine,Lee, Laksh,Malik, Breeana,Baker, Kamran,Salayev, Sughra,Guliyeva, Kimberley J,Billingsley, Henry,Houlden, Andrew B,Singleton, Cornelis,Blauwendraat, Sara,Bandres-Ciga, Rauan,Kaiyrzhanov

Movement disorders : official journal of the Movement Disorder Society · 2025-08-01

pmid:40751262

Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement.

Christy W,LaFlamme, Cassandra,Rastin, Soham,Sengupta, Helen E,Pennington, Sophie J,Russ-Hall, Amy L,Schneider, Emily S,Bonkowski, Edith P,Almanza Fuerte, Talia J,Allan, Miranda Perez-Galey,Zalusky, Joy,Goffena, Sophia B,Gibson, Denis M,Nyaga, Nico,Lieffering, Malavika,Hebbar, Emily V,Walker, Daniel,Darnell, Scott R,Olsen, Pandurang,Kolekar, Mohamed Nadhir,Djekidel, Wojciech,Rosikiewicz, Haley,McConkey, Jennifer,Kerkhof, Michael A,Levy, Raissa,Relator, Dorit,Lev, Tally,Lerman-Sagie, Kristen L,Park, Marielle,Alders, Gerarda,Cappuccio, Nicolas,Chatron, Leigh,Demain, David,Genevieve, Gaetan,Lesca, Tony,Roscioli, Damien,Sanlaville, Matthew L,Tedder, Sachin,Gupta, Elizabeth A,Jones, Monika,Weisz-Hubshman, Shamika,Ketkar, Hongzheng,Dai, Kim C,Worley, Jill A,Rosenfeld, Hsiao-Tuan,Chao, Geoffrey,Neale, Gemma L,Carvill, Zhaoming,Wang, Samuel F,Berkovic, Lynette G,Sadleir, Danny E,Miller, Ingrid E,Scheffer, Bekim,Sadikovic, Heather C,Mefford

Nature communications · 2024-08-06

pmid:39107278

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)