Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an expansion of CTG repeats in the 3' UTR of the DMPK gene. The subject is an 11-year-old girl with atypical myopathy. Because the proband's family has a positive DM1 history, a molecular-genetic analysis for DM1 was performed. This study showed that proband had a small DMPK expansion (91 CTG repeats) although the observed myopathy would not normally be associated with DM1. These results show how the phenotypic manifestation of DM1 can have unusual symptoms with a completely unexpected relationship to genotype.
Myotonic dystrophy type 1 (MD1) is the most common form of muscular dystrophy in adults. MD1 is caused by the expansion of CTG repeats in the DMPK gene and affects various organs beyond muscles. We present a case of a patient with MD1 exhibiting features of metabolic syndrome (MetS), including insulin resistance and dyslipidemia.
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
Myotonic dystrophy type 1 (DM1) is a dominantly inherited multi-system disease caused by expanded CTG repeats in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Similar to other repeat disorders, the expanded trinucleotide repeat is unstable and demonstrates a tendency to increase repeat size with age in affected tissues. DNA mismatch repair system is implicated in somatic instability.
Objective: An intronic cytosine-thymine-guanine (CTG) triplet repeat expansion in the transcription factor 4 gene () gene (CTG18.1) confers significant risk for the development of Fuchs' endothelial corneal dystrophy (FECD). The objective of this study was to conduct an unbiased survey of the CTG18.
Accurately quantifying the functional consequences of noncoding mosaic variants requires the pairing of DNA sequences with both accessible and closed chromatin architectures along individual DNA molecules-a pairing that cannot be achieved using traditional fragmentation-based chromatin assays. We demonstrate that targeted single-molecule chromatin fiber sequencing (Fiber-seq) achieves this, permitting single-molecule, long-read genomic, and epigenomic profiling across targeted >100 kb loci with ∼10-fold enrichment over untargeted sequencing. Targeted Fiber-seq reveals that pathogenic expansions of the CTG repeat that underlie Myotonic Dystrophy 1 are characterized by somatic instability and disruption of multiple nearby regulatory elements, both of which are repeat length-dependent.
Background: The expansion of CAG/CTG repeats in functionally unrelated genes is a causative factor in many inherited neurodegenerative disorders, including Huntington's disease (HD), spinocerebellar ataxias (SCAs), and myotonic dystrophy type 1 (DM1). Despite many years of research, the mechanism responsible for repeat instability is unknown, and recent findings indicate the key role of DNA repair in this process. The repair of DSBs induced by genome editing tools results in the shortening of long CAG/CTG repeats in yeast models.
