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. It has also been linked to Autism and related traits, especially in individuals with earlier onset^2,3,4,5,6,7.

Prevalence

9.27 100,000

5-20/100,000⁸. 0.5-18.1/100,000⁹; 6.5/100,000¹⁰. 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000¹¹. Found across ethnicities/ancestries, with population-dependent prevalence⁸.

Age of Onset Details

Typical: 10-30⁸; Range: 0-74¹².

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 review¹³. Intermediate alleles (35-49) associated with premutation⁸. 3%-8% of DM1 expansions contain interrupting variant repeats such as CCG and CGG, associated with later onset and milder phenotype; the variant repeat GCGGCA has also been reported^14,15. In another study, interruptions of the CTG repeat with CCG, GGC, CTC or CAG motifs are estimated to occur in 3-11% of DM1 patients¹⁶. Expansions within gene ZNF850 may function as DM1 modifiers¹⁷. Flanking PCR detects alleles up to ~150 repeats, while RP-PCR may detect missed expanded alleles^8,18. Southern blotting approximates the size of large expansions¹⁹, while long read sequencing resolves repeat size and structure²⁰.

Mechanism

GoF

RNA gain-of-function: RNA gelation leading to misregulation of alternative splicing²¹. Expanded DMPK r(CUG)n RNA forms a hairpin containing periodic 1*1 U/U internal loops that engage/sequester MBNL family RNA-binding proteins, especially MBNL1, disrupting pre mRNA processing and contributing to cardiac phenotypes²². Loss of MBNL proteins has been linked to mis-splicing of Autism spectrum-risk genes such as SCN2A, ANK2, and SHANK2, possibly leading to Autism-related traits². Evidence suggests that disulfide bond-dependent MBNL1/MBNL2 dimerization maintains toxic RNA foci²³.

Year

1992²⁴

Location in Gene

3' UTR

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

Autism-related traits in myotonic dystrophy type 1 model mice are due to MBNL sequestration and RNA mis-splicing of autism-risk genes.

Łukasz J,Sznajder, Mahreen,Khan, Adam,Ciesiołka, Mariam,Tadross, Curtis A,Nutter, Katarzyna,Taylor, Christopher E,Pearson, Mark H,Lewis, Rochelle M,Hines, Maurice S,Swanson, Krzysztof,Sobczak, Ryan K C,Yuen

Nature neuroscience · 2025-04-21

pmid:40259070

Childhood-onset form of myotonic dystrophy type 1 and autism spectrum disorder: Is there comorbidity?

N,Angeard, E,Huerta, A,Jacquette, D,Cohen, J,Xavier, M,Gargiulo, L,Servais, B,Eymard, D,Héron

Neuromuscular disorders : NMD · 2017-12-15

pmid:29361396

Asperger syndrome associated with Steinert's myotonic dystrophy.

T A,Blondis, E,Cook, P,Koza-Taylor, T,Finn

Developmental medicine and child neurology · 1996-09-01

pmid:8810716

Expanded

Zuzana,Musova, Miroslava,Hancarova, Marketa,Havlovicova, Radka,Pourova, Michal,Hrdlicka, Josef,Kraus, Marie,Trkova, David,Stejskal, Zdenek,Sedlacek

Neuropsychiatric disease and treatment · 2016-09-19

pmid:27695335

Myotonic dystrophy type 1: clinical manifestations in children and adolescents.

Genevieve,Ho, Kate A,Carey, Michael,Cardamone, Michelle A,Farrar

Archives of disease in childhood · 2018-06-05

pmid:29871899

Cognitive function, behaviour and quality of life in children with myotonic dystrophy type 1 in South - Eastern Norway.

Petra,Aden, Anne-Britt,Skarbø, Sean,Wallace, Kristin,Ørstavik, Magnhild,Rasmussen

European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · 2023-05-13

pmid:37209486

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

Advancing 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 · 2024-12-29

pmid:39710066

High Resolution Analysis of

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

Genes · 2022-05-28

pmid:35741732

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 · 2025-02-08

pmid:39679849

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

MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model.

Rong-Chi,Hu, Yi,Zhang, Larissa,Nitschke, Sara J,Johnson, Ayrea E,Hurley, William R,Lagor, Zheng,Xia, Thomas A,Cooper

The Journal of clinical investigation · 2025-02-11

pmid:39932794

Muscleblind-like proteins dimerize by forming disulfide bonds to regulate alternative splicing and pathogenic RNA foci formation.

Luke A,Knudson, Adam,Kosti, Kathryn R,Moss, Liang,Shi, GiaLinh N,Nguyen, Aleksandra,Janusz-Kaminska, Eric X,Zhou, Ryan P,Hildebrandt, Eric T,Wang, Gary J,Bassell

bioRxiv : the preprint server for biology · 2026-03-26

pmid:41929128

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)

Advancing 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 · 2024-12-29

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 · 2025-02-08

pmid:39679849

Detection of large expansions in myotonic dystrophy type 1 using triplet primed PCR.

Susmita,Singh, Amy,Zhang, Stephen,Dlouhy, Shaochun,Bai

Frontiers in genetics · 2014-04-24

pmid:24795756

Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2.

Erik-Jan,Kamsteeg, Wolfram,Kress, Claudio,Catalli, Jens M,Hertz, Martina,Witsch-Baumgartner, Michael F,Buckley, Baziel G M,van Engelen, Marianne,Schwartz, Hans,Scheffer

European journal of human genetics : EJHG · 2012-05-30

pmid:22643181

Targeted long-read sequencing for high-resolution repeat profiling in myotonic dystrophy type 1.

Yoojung,Han, Ja-Hyun,Jang, Hyeshik,Chang

Experimental & molecular medicine · 2026-04-13

pmid:41974889

Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.

Mohamed,Chahine, Vamsi Krishna Murthy,Ginjupalli, Dominic,Jauvin, Mohamed,Boutjdir

Molecular diagnosis & therapy · 2026-04-17

pmid:41996006

Population-scale repeat expansions elucidate disease risk and brain atrophy.

Vijay Kumar,Pounraja, Jae Hoon,Sul, Joseph,Herman, Sean,O'Keeffe, Veera,Rajagopal, Xiaodong,Bai, Michael D,Kessler, Neelroop,Parikshak, Karl,Landheer, Xingmin,Zhang, Sean,Yu, Lance,Zhang, Michelle G,LeBlanc, Jennifer,Rico-Varela, Frederic,Grau, Sarah,Wolf, Sriramkumar,Sundaramoorthy, Farshid,Sepehrband, Eli A,Stahl, Yuda,Huo, Mohsin,Ahmed, Susan,Croll, William,Salerno, John D,Overton, Jonathan,Marchini, Jeffrey,Reid, Luca A,Lotta, Aris,Baras, Goncalo R,Abecasis, Giovanni,Coppola, Sahar,Gelfman

Nature · 2026-04-08

pmid:41951733

Generation and characterization of two human induced pluripotent stem cell lines from myotonic dystrophy type 1 patients.

Pooja,Darji, Wenqiang,Liu, Wenshu,Zeng, Jade T,Chao, Paul D,Pang, Matthew T,Wheeler, Marco,Perez, Joseph C,Wu

Stem cell research · 2026-04-01

pmid:41946260

Progressive cardiac phenotypes and reduced reversibility from long-term CUGexp RNA expression in a DM1 mouse model.

Rong-Chi,Hu, Mohammadreza,Tabary, Xander Ht,Wehrens, Thomas A,Cooper

JCI insight · 2026-03-19

pmid:41855125