DM1_DMPK
- Gene
- DMPK
- Disease
- DM1
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 18
- Publications Reviewed
- 7
- Publication Span
- 30.58 years
- Last Updated
- 07/21/2025
- Curator(s)
- Laurel Hiatt
Description
Myotonic dystrophy type 1 (DM1) is an autosomal dominant, multisystem repeat-expansion disorder caused by a pathogenic CTG expansion in the 3' UTR of DMPK. The locus-disease relationship is supported by molecularly confirmed DMPK CTG expansions in affected probands, population/control allele data, repeat-length and repeat interruptions that modify age at onset and severity, and experimental evidence showing toxic expanded CUG RNA with nuclear foci, RNA-binding protein sequestration, disease-relevant cellular and mouse phenotypes, and partial rescue after modulation of pathogenic RNA-binding pathways.
Genetic evidence
Total: 12
| Collective Evidence | Allele | PMID:32851192 PMID:39643839 | 2 | PMID:32851192 showed that DM1 individuals with repeat interruptions had milder motor/neurocognitive/behavioral outcomes than matched pure-repeat DM1 cases. PMID:39643839 summarizes that DMPK CTG expansion length influences disease severity/age at onset, while variant interruptions and somatic instability modify phenotype. |
| Singular Evidence | Probands | PMID:20635151 | 6 | In a Mexican cohort of 50 clinically/electrophysiologically diagnosed DM1 patients, 45/50 (90%) had pathogenic DMPK CTG expansions detected by fluorescent PCR plus TP-PCR/capillary electrophoresis; 400 unrelated controls showed non-expanded alleles ranging from 5 to 34 repeats. |
| Statistics | Case-control data | PMID:7847063 | 4 | Case-control study was carried out on 25 patients with myotonic dystrophy (MyD) and 25 healthy subjects (p < 0.0001). |
Experimental evidence
Total: 6
| Rescue | Rescue in non-human model organism | PMID:39932794 | 2 | In CUG960 heart-specific DM1 mice expressing 960 interrupted CUG repeats in the human DMPK 3' UTR, AAV9-mediated MBNL1 and/or MBNL2 overexpression partially rescued conduction delays, contractile dysfunction, hypertrophy, and misregulated splicing/gene expression. |
| Rescue | Rescue in cell culture | PMID:16027111 | 1 | In 293T cells and myoblasts expressing an EGFP-(CUG)85 reporter, siRNA knockdown of hnRNP H restored EGFP expression and relieved nuclear retention of expanded CUG-repeat RNA; hnRNP H binding required expanded CUG repeats and a distal branch point. |
| Models | Non-human model organism | PMID:31649961 | 2 | DMSXL transgenic mice carrying a human DM1 allele with ~CTG1300 repeats yielded ALP-positive skeletal muscle pericytes that expressed transgenic DMPK and showed nuclear CUG RNA foci, averaging 1-2 foci/nucleus in heterozygotes and 5-10 in homozygotes. |
| Functional Alteration | Patient cells | PMID:31649961 | 1 | ALP-positive skeletal muscle pericytes were isolated from six DM1 patients and two unaffected controls; patient pericytes showed nuclear CUG RNA foci with MBNL1 colocalization in several lines while maintaining proliferation and myogenic differentiation potential comparable to controls. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.