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.

Mechanism

GoF

RNA gain-of-function: RNA gelation leading to misregulation of alternative splicing¹⁸. Expanded-repeat RNA sequesters the muscleblind-like (MBNL) family of RNA-binding proteins as part of the disruption of pre-mRNA processing, contributing to cardiac phenotypes¹⁹. 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

Year

1992²⁰

Gene Strand

Alleles

Ref. Motif

CAG

Pathogenic (ref.)

CAG

Pathogenic (gene)

CTG

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: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 · 2025-02-01

doi:10.1016/j.mcp.2024.102005

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 · 2024-12-16

doi:10.1093/hmg/ddae186

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

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)

A genome-wide approach for the discovery of novel repeat expansion disorders in the Undiagnosed Diseases Network cohort.

Sarah,Fazal, Harriet,Dashnow, Maike F,Dohrn, Jacquelyn,Raposo, Laurel,Hiatt, Matt C,Danzi, Isaac R L,Xu, Camilo,Toro, David R,Adams, Karen,Usdin, Bruce,Hayward, Shilpa Nadimpalli,Kobren, Shamil R,Sunyaev, Rebecca C,Spillmann, Vandana,Shashi, Adriana,Rebelo, Guney,Bademci, Mustafa,Tekin, Aaron R,Quinlan, Stephan,Züchner

Genetics in medicine : official journal of the American College of Medical Genetics · 2025-05-22

pmid:40417743

MSH2 is not required for either maintenance of DNA methylation or repeat contraction at the FMR1 locus in fragile X syndrome or the FXN locus in Friedreich's ataxia.

Jessalyn,Grant-Bier, Kathryn,Ruppert, Bruce,Hayward, Karen,Usdin, Daman,Kumari

Epigenetics & chromatin · 2025-04-28

pmid:40296143

Optical genome mapping enables accurate testing of large repeat expansions.

Bart,van der Sanden, Kornelia,Neveling, Syukri,Shukor, Michael D,Gallagher, Joyce,Lee, Stephanie L,Burke, Maartje,Pennings, Ronald,van Beek, Michiel,Oorsprong, Ellen,Kater-Baats, Eveline,Kamping, Alide A,Tieleman, Nicol C,Voermans, Ingrid E,Scheffer, Jozef,Gecz, Mark A,Corbett, Lisenka E L M,Vissers, Andy Wing Chun,Pang, Alex,Hastie, Erik-Jan,Kamsteeg, Alexander,Hoischen

Genome research · 2025-04-14

pmid:40113266

Influence of CTG repeats from the human DM1 locus on murine gut microbiota.

Manijeh,Mahdavi, Tae-Yeon,Kim, Karine,Prévost, Philippe,Balthazar, Valérie,Gagné-Ouellet, Isabelle Fissette-Paul,Hus, Élise,Duchesne, Séréna,Harvey, Cynthia,Gagnon, Isabelle,Laforest-Lapointe, Nicolas A,Dumont, Eric,Massé

Computational and structural biotechnology journal · 2025-02-19

pmid:40092662

Analysis of Short Tandem Repeat Expansions in a Cohort of 12,496 Exomes from Patients with Neurological Diseases Reveals Variable Genotyping Rate Dependent on Exome Capture Kits.

Clarissa,Rocca, David,Murphy, Chris,Clarkson, Matteo,Zanovello, Delia,Gagliardi, Queen Square,Genomics, Rauan,Kaiyrzhanov, Javeria,Alvi, Reza,Maroofian, Stephanie,Efthymiou, Tipu,Sultan, Jana,Vandrovcova, James,Polke, Robyn,Labrum, Henry,Houlden, Arianna,Tucci

Genes · 2025-01-28

pmid:40004498

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

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 · 2025-02-03

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