Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

High Resolution Analysis of DMPK Hypermethylation and Repeat Interruptions in Myotonic Dystrophy Type 1

Research output: Contribution to journalJournal articlepeer-review

DOI

  1. Cathepsin C Regulates Cytokine-Induced Apoptosis in β-Cell Model Systems

    Research output: Contribution to journalJournal articlepeer-review

  2. EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder

    Research output: Contribution to journalJournal articlepeer-review

  3. Candidate Genes and Pathways Associated with Gilles de la Tourette Syndrome-Where Are We?

    Research output: Contribution to journalReviewpeer-review

  1. Three novel FHL1 Variants cause a mild Phenotype of Emery-Dreifuss Muscular Dystrophy

    Research output: Contribution to journalJournal articlepeer-review

  2. Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease

    Research output: Contribution to journalJournal articlepeer-review

  3. Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder

    Research output: Contribution to journalJournal articlepeer-review

View graph of relations

Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder caused by the expansion of a CTG repeat in the 3'-UTR of DMPK, which is transcribed to a toxic gain-of-function RNA that affects splicing of a range of genes. The expanded repeat is unstable in both germline and somatic cells. The variable age at disease onset and severity of symptoms have been linked to the inherited CTG repeat length, non-CTG interruptions, and methylation levels flanking the repeat. In general, the genetic biomarkers are investigated separately with specific methods, making it tedious to obtain an overall characterisation of the repeat for a given individual. In the present study, we employed Oxford nanopore sequencing in a pilot study to simultaneously determine the repeat lengths, investigate the presence and nature of repeat interruptions, and quantify methylation levels in the regions flanking the CTG-repeats in four patients with DM1. We determined the repeat lengths, and in three patients, we observed interruptions which were not detected using repeat-primed PCR. Interruptions may thus be more common than previously anticipated and should be investigated in larger cohorts. Allele-specific analyses enabled characterisation of aberrant methylation levels specific to the expanded allele, which greatly increased the sensitivity and resolved cases where the methylation levels were ambiguous.

Original languageEnglish
Article number970
JournalGenes
Volume13
Issue number6
ISSN2073-4425
DOIs
Publication statusPublished - 28 May 2022

    Research areas

  • Humans, Myotonic Dystrophy/diagnosis, Myotonin-Protein Kinase/genetics, Pilot Projects, RNA Splicing, Trinucleotide Repeat Expansion/genetics

ID: 79082961