ArticleHuman molecular genetics2023
Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- CRISPR/dCas9-mediated tuning of DMPK transcription reveals a quantitative relationship between toxic repeat RNA expression and MBNL1 activity in myotonic dystrophy.Human molecular genetics · 2026Article
- Defining Haplosufficiency in Autosomal Recessive Limb-Girdle Muscular Dystrophy Using Molecular Markers in Disease Carriers.Neurology. Genetics · 2026Article
- Generation and characterization of two human induced pluripotent stem cell lines from myotonic dystrophy type 1 patients.Stem cell research · 2026Article
- Elimination of myotonia improves myopathy in a muscleblind-like knockout model of myotonic dystrophy.Nature communications · 2026Article
- Delpacibart etedesiran improves the molecular pathology of myotonic dystrophy type 1 in the phase 1/2 MARINA study.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Changes in RNA splicing as a surrogate endpoint for myotonic dystrophy Type 1 (DM1) clinical trials.Journal of neuromuscular diseases · 2026Review
- Toward Trial Readiness in Congenital Myotonic Dystrophy: A Longitudinal Cohort Study of Predictors of Motor Function in Childhood.Neurology. Genetics · 2026Article
- Co-Opting MBNL-Dependent Alternative Splicing Cassette Exons to Control Gene Therapy in Myotonic Dystrophy.Annals of neurology · 2026Article
- Differential pathology and susceptibility to MBNL loss across muscles in myotonic dystrophy mouse models.JCI insight · 2025Article
- Elimination of myotonia improves myopathy in a muscleblind knockout model of myotonic dystrophy.bioRxiv : the preprint server for biology · 2025Article
- Repeat length as a key determinant for disease severity and antisense oligonucleotide activity in myotonic dystrophy type 1.Molecular therapy. Methods & clinical development · 2025Article
- circARHGAP10 as a candidate biomarker and therapeutic target in myotonic dystrophy type 1.Molecular therapy. Nucleic acids · 2025Article
- Neonatal congenital myotonic dystrophy with DMPK gene expansion: clinical features and short-term outcomes.Frontiers in pediatrics · 2025Article
- Transcriptional Changes Associated with Amyoplasia.International journal of molecular sciences · 2024Article
- Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in theInternational journal of molecular sciences · 2024Article
- RNA mis-splicing in children with congenital myotonic dystrophy is associated with physical function.Annals of clinical and translational neurology · 2024Article
- Revealing myopathy spectrum: integrating transcriptional and clinical features of human skeletal muscles with varying health conditions.Communications biology · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by expansion of CTG microsatellite repeats within DMPK. The most severe form, congenital myotonic dystrophy (CDM), has symptom onset at birth due to large intergenerational repeat expansions. Despite a common mutation, CDM individuals present with a distinct clinical phenotype and absence of common DM1 symptoms. Given the clinical divergence, it is unknown if the hallmark of DM1 pathology, dysregulation of alternative splicing (AS) due to sequestration of MBNL proteins within toxic CUG repeat RNAs, contributes to disease throughout pediatric development. To evaluate global transcriptomic dysregulation, RNA-seq was performed on 36 CDM skeletal muscle biopsies ages 2 weeks to 16 years, including two longitudinal samples. Fifty DM1 and adult/pediatric controls were also sequenced as comparative groups. Despite a large CTG expansion and shared age of onset, CDM individuals presented with a heterogenous, MBNL-dependent mis-splicing signature. Estimation of intracellular MBNL concentrations from splicing responses of select events correlated with total spliceopathy and revealed a distinct, triphasic pattern of AS dysregulation across pediatric development. CDM infants (< 2 years) possess severe mis-splicing that significantly improves in early childhood (2-8 years) independent of sex or CTG repeat load. Adolescent individuals (8-16 years) stratified into two populations with a full range of global splicing dysregulation. DMPK expression changes correlated with alterations in splicing severity during development. This study reveals the complex dynamics of the CDM muscle transcriptome and provides insights into new therapeutic strategies, timing of therapeutic intervention, and biomarker development.
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