Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients

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Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients.

Myotonic dystrophy type 1 (DM1) is caused by the expansion of a (CTG).(CAG) repeat in the DMPK gene on chromosome 19q13.3. At least 17 neurological diseases have similar genetic mutations, the expansion of DNA repeats. In most of these disorders, the disease severity is related to the length of the repeat expansion, and in DM1 the expanded repeat undergoes further elongation in somatic and germ...

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Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying >1,000 CTG Repeats from the Human DM1 Locus

Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. I...

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Transcriptionally Repressive Chromatin Remodelling and CpG Methylation in the Presence of Expanded CTG-Repeats at the DM1 Locus

An expanded CTG-repeat in the 3' UTR of the DMPK gene is responsible for myotonic dystrophy type I (DM1). Somatic and intergenerational instability cause the disease to become more severe during life and in subsequent generations. Evidence is accumulating that trinucleotide repeat instability and disease progression involve aberrant chromatin dynamics. We explored the chromatin environment in r...

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DM1 Patients with Small CTG Expansions are also at Risk of Severe Conduction Abnormalities.

BACKGROUND AND OBJECTIVES A high risk of cardiac arrhythmias was reported in myotonic dystrophy type 1 (DM1). The purpose of the study was to evaluate the risk of severe electrocardiographic abnormalities in DM1 patients with small CTG expansions. METHODS We assessed the ECG done at DM1 diagnosis for 127 patients with ≤200 CTG repeats and for 82 of them who had ≥1 ECG over a period of follow-...

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CRISPR/Cas9-Mediated Deletion of CTG Expansions Recovers Normal Phenotype in Myogenic Cells Derived from Myotonic Dystrophy 1 Patients

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, characterized by progressive myopathy, myotonia, and multi-organ involvement. This dystrophy is an inherited autosomal dominant disease caused by a (CTG)n expansion within the 3' untranslated region of the DMPK gene. Expression of the mutated gene results in production of toxic transcripts that aggregate as nucle...

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ژورنال

عنوان ژورنال: Nucleic Acids Research

سال: 2004

ISSN: 1362-4962

DOI: 10.1093/nar/gki147