EPM1 CSTB

Unverricht-Lundborg disease (ULD) is a rare progressive myoclonic epilepsy disorder characterized by action- and stimulus-sensitive myoclonus, and tonic-clonic seizures with ataxia, but with only a mild cognitive decline over time¹.

Prevalence

Worldwide prevalence unknown; Finland prevalence 2-4/100,000. Found across ethnicities/ancestries, with population-dependent prevalence; highest in Tunisia, Algeria, Morocco, and Finland².

Age of Onset Details

Typical: 6-15²; Range: 6-18³.

Locus

hg19

chr21:45196323-45196360

hg38

chr21:43776442-43776479

t2t

chr21:42132054-42132091

Details

Affected individuals have an unstable 12-nucleotide (dodecomer) repeat expansion. Alleles containing 2-3 motifs are considered benign, while alleles with 30-125 repeats are fully penetrant³. Alleles in the range 12-17 repeats have been observed, however the individuals carrying them have not undergone clinical evaluation. Alleles in the range 4-11 and 18-29 repeats have not been reported to date.

Mechanism

LoF

The repeat expanison causes significantly reduced expression of cystatin-B protein².

Year

1997⁴

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CGCGGGGCGGGG

Pathogenic (ref.)

CGCGGGGCGGGG

Pathogenic (gene)

CCCCGCCCCGCG

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0009698

Progressive Myoclonic Epilepsy Type 1

Anna-Elina,Lehesjoki, Reetta,Kälviäinen

GeneReviews® · 1993-01-01

genereviews:NBK1142

Clinical picture of EPM1-Unverricht-Lundborg disease.

Reetta,Kälviäinen, Jelena,Khyuppenen, Päivi,Koskenkorva, Kai,Eriksson, Ritva,Vanninen, Esa,Mervaala

Epilepsia · 2008-03-05

pmid:18325013

Dodecamer repeat expansion in cystatin B gene in progressive myoclonus epilepsy.

M D,Lalioti, H S,Scott, C,Buresi, C,Rossier, A,Bottani, M A,Morris, A,Malafosse, S E,Antonarakis

Nature · 1997-04-24

pmid:9126745

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)

Novel, complex configurations of the

Mark F,Bennett, Mark A,Corbett, Thessa,Kroes, Laura,Canafoglia, Karen L,Oliver, Jillian M,Cameron, Neblina,Sikta, Jacob,Munro, Liam G,Fearnley, Kristina,Ibañez, Arianna,Tucci, Sanjay M,Sisodiya, Michael S,Hildebrand, Ingrid E,Scheffer, Carolina,Courage, Anna-Elina,Lehesjoki, Loretta,Giuliano, Giuseppe,Didato, Silvana,Franceschetti, Jozef,Gecz, Samuel F,Berkovic, Melanie,Bahlo

Brain communications · 2025-11-03

pmid:41268177

Epilepsy in dentatorubral-pallidoluysian atrophy: A systematic review and meta-analysis.

Toru,Horinouchi, Haruka,Ishibashi, Yukako,Nakagami, Yoko,Kobayashi Takahashi, Takato,Akiba, Masaharu,Miyauchi, Naohiro,Yamamoto, Ryoichi,Inoue, Satoshi,Kodama, Takafumi,Kubota, Naoto,Kuroda

Epilepsia · 2025-10-28

pmid:41147955

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

A novel c.116 - 117 del variant in Unverricht-Lundborg disease: first ULD report in large Chinese population and review of the pathogenetic variants in CSTB gene.

Pu,Miao, Yao,Ding, Zhidong,Cen, Yulan,Chen, Wei,Luo, Baorong,Zhang, Zhiying,Wu, Meiping,Ding, Shuang,Wang

Acta epileptologica · 2025-05-29

pmid:40442775

Approach to Progressive Myoclonic Epilepsies: Clinical Clues for Genetic Testing.

Prasanthi,Aripirala, Sujit Abajirao,Jagtap

Journal of child neurology · 2025-05-08

pmid:40340521

Discovery of a Novel Shared Variant Among

Sima,Chaudhari, Lavanya Prakash,Acharya, Dushyanth Babu,Jasti, Akshay Pramod,Ware, Sankar Prasad,Gorthi, Kapaettu,Satyamoorthy

International journal of genomics · 2024-08-10

pmid:39156922

CSTB gene replacement improves neuroinflammation, neurodegeneration and ataxia in murine type 1 progressive myoclonus epilepsy.

Emrah,Gumusgoz, Sahba,Kasiri, Mayank,Verma, Jun,Wu, Daniel,Villarreal Acha, Ummay,Marriam, Sharyl,Fyffe-Maricich, Amy,Lin, Xin,Chen, Steven J,Gray, Berge A,Minassian

Gene therapy · 2023-12-22

pmid:38135787

Short- and long-interval intracortical inhibition in EPM1 is related to genotype.

Katri,Silvennoinen, Laura,Säisänen, Jelena,Hyppönen, Saara M,Rissanen, Pasi A,Karjalainen, Sasha,D'Ambrosio, Diego,Jimenez-Jimenez, Sara,Zagaglia, John C,Rothwell, Simona,Balestrini, Sanjay M,Sisodiya, Petro,Julkunen, Esa,Mervaala, Reetta,Kälviäinen

Epilepsia · 2022-12-01

pmid:36398398

Insights into the Genetic Profile of Two Siblings Affected by Unverricht-Lundborg Disease Using Patient-Derived hiPSCs.

Valeria,Lucchino, Luana,Scaramuzzino, Stefania,Scalise, Michela,Lo Conte, Clara,Zannino, Giorgia Lucia,Benedetto, Umberto,Aguglia, Edoardo,Ferlazzo, Giovanni,Cuda, Elvira Immacolata,Parrotta

Cells · 2022-11-04

pmid:36359887