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

Pathogenic Genotype (%): % of individuals predicted to be affected based on their genotype

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)

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

Clinical and molecular characterization of Unverricht-Lundborg disease among Egyptian patients.

Hassan,Hosny, Mohamed,El Tamawy, Riyad,Gouider, Gaetan,Lesca, Maged,Abdel Naseer, Nirmeen,Kishk, Mohamed S,Abdel-Hamid, Ayman,Ashmawi

Epilepsy research · 2021-08-25

pmid:34474241

Genetic testing and the phenotype of Polish patients with Unverricht-Lundborg disease (EPM1) - A cohort study.

Magdalena,Bosak, Anna,Sułek, Maria,Łukasik, Amadeusz,Żak, Agnieszka,Słowik, Anetta,Lasek-Bal

Epilepsy & behavior : E&B · 2020-09-10

pmid:32920378

ASAH1-related disorders: Description of 15 novel pediatric patients and expansion of the clinical phenotype.

Iman G,Mahmoud, Mohamed A,Elmonem, Maha S,Zaki, Areef,Ramadan, Nihal M,Al-Menabawy, Aya,El-Gamal, Lobna,Mansour, Mahmoud Y,Issa, Mohamed S,Abdel-Hamid, Sawsan,Abdel-Hady, Iman,Khalifa, Ahmed,Ibrahim, Alexander,Solyom, Arndt,Rolfs, Laila,Selim

Clinical genetics · 2020-09-02

pmid:32875576