DM1 DMPK

Steinert disease, also known as myotonic dystrophy type 1, is a muscle disease characterized by myotonia and by multiorgan damage that combines various degrees of muscle weakness, arrhythmia and/or cardiac conduction disorders, cataract, endocrine damage, sleep disorders and baldness¹.

Prevalence

9.27 100,000

5-20/100,000². 0.5-18.1/100,000³; 6.5/100,000⁴. 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000⁵. Found across ethnicities/ancestries, with population-dependent prevalence².

Age of Onset Details

Typical: 10-30²; Range: 0-74⁶.

Locus

hg19

chr19:46273462-46273524

hg38

chr19:45770204-45770266

t2t

chr19:48597739-48597756

Details

Overview of disease locus through 2024, including largest pathogenic allele of 4,000, described in Rimoldi et al review⁷. Intermediate alleles (35-49) associated with premutation². 3%-8% of DM1 expansions contain variant repeats such as CCG and CGG, associated with later onset and milder phenotype⁸. In another study, interruptions of the CTG repeat with CCG, GGC, CTC or CAG motifs are estimated to occur in 3-11% of DM1 patients⁹.

Mechanism

GoF

RNA gain-of-function: RNA gelation leading to misregulation of alternative splicing¹⁰.

Year

1992¹¹

Gene Strand

Alleles

Ref. Motif

CAG

Pathogenic (ref.)

CAG

Pathogenic (gene)

CTG

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008056

Myotonic Dystrophy Type 1

Thomas D.,Bird

GeneReviews® · 1993-01-01

genereviews:NBK1165

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care.

Marie,De Antonio, Céline,Dogan, Ferroudja,Daidj, Bruno,Eymard, Jack,Puymirat, Jean,Mathieu, Cynthia,Gagnon, Sandrine,Katsahian, Dalil,Hamroun, Guillaume,Bassez

Orphanet journal of rare diseases · 2019-06-03

pmid:31159885

Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis.

Qiao,Liao, Yihao,Zhang, Jian,He, Kun,Huang

Neuroepidemiology · 2022-04-28

pmid:35483324

Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

Huahua,Zhong, Li,Zeng, Xuefan,Yu, Qing,Ke, Jihong,Dong, Yan,Chen, Lijun,Luo, Xueli,Chang, Junhong,Guo, Yiqi,Wang, Hui,Xiong, Rongrong,Liu, Changxia,Liu, Jibao,Wu, Jie,Lin, Jianying,Xi, Wenhua,Zhu, Song,Tan, Fuchen,Liu, Jiahong,Lu, Chongbo,Zhao, Sushan,Luo

Orphanet journal of rare diseases · 2024-03-07

pmid:38454488

Myotonic dystrophies: an update on clinical features, molecular mechanisms, management, and gene therapy.

Martina,Rimoldi, Sabrina,Lucchiari, Serena,Pagliarani, Giovanni,Meola, Giacomo Pietro,Comi, Elena,Abati

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024-12-07

pmid:39643839

Variant repeats within the

Jacob N,Miller, Ellen,van der Plas, Mark,Hamilton, Timothy R,Koscik, Laurie,Gutmann, Sarah A,Cumming, Darren G,Monckton, Peggy C,Nopoulos

Neurology. Genetics · 2020-08-12

pmid:32851192

High Resolution Analysis of

Astrid,Rasmussen, Mathis,Hildonen, John,Vissing, Morten,Duno, Zeynep,Tümer, Ulf,Birkedal

Genes · 2022-05-28

pmid:35741732

Clinical and neuroimaging review of triplet repeat diseases.

Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe

Japanese journal of radiology · 2022-09-28

pmid:36169768

Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member.

J D,Brook, M E,McCurrach, H G,Harley, A J,Buckler, D,Church, H,Aburatani, K,Hunter, V P,Stanton, J P,Thirion, T,Hudson

Cell · 1992-02-21

pmid:1310900

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)

High-resolution repeat structure analysis in molecular diagnostics of myotonic dystrophy type 1 using short-read whole genome sequencing.

Ingrid,Lojova, Marcel,Kucharik, Zuzana,Pös, Andrej,Balaz, Andrea,Zatkova, Eva Tothova,Tarova, Jaroslav,Budis, Ludevit,Kadasi, Tomas,Szemes, Jan,Radvanszky

Molecular and cellular probes · 2024-12-20

pmid:39710066

Identification of ZNF850 as a novel CTG repeat expansion-related gene in myotonic dystrophy type 1 patient-derived iPSCs.

Masayoshi,Kamon, Shuji,Wakatsuki, Masayuki,Nakamori, Masanori P,Takahashi, Madoka,Mori-Yoshimura, Hirofumi,Komaki, Toshiyuki,Araki

Human molecular genetics · 2024-12-16

pmid:39679849

dmTGS: Precise Targeted Enrichment Long-Read Sequencing Panel for Tandem Repeat Detection.

Kang,Yang, Yue,Liu, Ji,Zhang, Qian,Yu, Feng,Xu, Jiyuan,Liu, Yuting,Li, Xiaojie,Zhang, Zhiqiang,Wang, Ning,Wang, Yuezhen,Li, Yan,Shi, Wan-Jin,Chen

Clinical chemistry · 2024-11-04

pmid:39492694

Altered drug metabolism and increased susceptibility to fatty liver disease in a mouse model of myotonic dystrophy.

Zachary,Dewald, Oluwafolajimi,Adesanya, Haneui,Bae, Andrew,Gupta, Jessica M,Derham, Ullas V,Chembazhi, Auinash,Kalsotra

Nature communications · 2024-10-21

pmid:39433769

Small Molecule Screening Identifies HSP90 as a Modifier of RNA Foci in Myotonic Dystrophy Type 1.

Sara J,Johnson, Hannah L,Johnson, Reid T,Powell, Clifford,Stephan, Fabio,Stossi, Thomas A,Cooper

Molecular and cellular biology · 2024-10-17

pmid:39415708

CTG repeat length underlying cardiac events and sudden death in myotonic dystrophy type 1.

Hideki,Itoh, Takashi,Hisamatsu, Kazuhiko,Segawa, Toshiaki,Takahashi, Takumi,Sato, Hiroto,Takada, Satoshi,Kuru, Chizu,Wada, Mikiya,Suzuki, Takuhisa,Tamura, Shugo,Suwazono, Koichi,Kimura, Tsuyoshi,Matsumura, Masanori P,Takahashi

European heart journal open · 2024-09-18

pmid:39391712

AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.

Estefanía,Cerro-Herreros, Judit,Núñez-Manchón, Neia,Naldaiz-Gastesi, Marc,Carrascosa-Sàez, Andrea,García-Rey, Diego Piqueras,Losilla, Irene,González-Martínez, Jorge,Espinosa-Espinosa, Kevin,Moreno, Javier,Poyatos-García, Juan J,Vilchez, Adolfo López,de Munain, Mònica,Suelves, Gisela,Nogales-Gadea, Beatriz,Llamusí, Rubén,Artero

Science advances · 2024-10-09

pmid:39383229

Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.

Renée H L,Raaijmakers, C Rosanne M,Ausems, Marieke,Willemse, Sarah A,Cumming, Baziel G M,van Engelen, Darren G,Monckton, Hans,van Bokhoven, Derick G,Wansink

Stem cell research & therapy · 2024-09-15

pmid:39278936

Hypogammaglobulinemia and infection risk in myotonic dystrophy type 1.

Shadi,El-Wahsh, Katrina,Morris, Sandhya,Limaye, Sean,Riminton, Alastair,Corbett, James D,Triplett

Muscle & nerve · 2024-09-12

pmid:39267217