-
The abnormal expansion of CTG repeats in the 3'-UTR of the DMPK gene elicits Myotonic Dystrophy 1, whereas elongated CCTG repeats in intron 1 of ZNF9 triggers Myotonic Dystrophy 2.
-
paired gRNA-CRISPR/Cas9 caused frequent inversion of expanded CTG repeats at the Dystrophia Myotonica protein kinase(DMPK) locus, and this approachwas not suitable for in vivo therapeutic genome editing.
-
Expanded CUG repeats in DMPK transcripts adopt diverse hairpin conformations without influencing the structure of the flanking sequences.
-
We have developed an inducible, skeletal muscle-specific mouse model of DM1 (CUG960) that expresses 960 CUG repeat-expressing animals (CUG960) in the context of human DMPK exons 11-15.
-
The motor function (MRCSS and 6MWT) and CTG repeat length of DMPK significantly correlated with LV diastolic dysfunction in patients with myotonic dystrophy type 1.
-
Variant repeats might explain a part of the phenotypic variability in a small percent of myotonic dystrophy type 1 patients and likely display a stabilizing effect on the meiotic instability of DMPK expanded alleles
-
Haplotype analysis using various polymorphic-markers in proximity to DMPK gene indicates that a single founder mutation originates myotonic dystrophy type 1 in Mexico; however, Y-STR haplogroups data and the presence of pre-mutated and large normal alleles in Amerindians support the hypothesis that both European and Amerindian ancestral chromosomes might have introduced the disease to the Mexican population.
-
Patients with myotonic dystrophy type 1 (DM1) may have a slight decrease in renal function that cannot be explained by a higher occurrence of risk factors for renal failure such as diabetes, hypertension or age. In addition, there was no correlation between CTG repeats, a marker of disease severity, and renal function.
-
Interruptions within the DMPK expanded alleles could also interfere with the chromatin structure, the transcriptional activity of the Myotonic dystrophy type 1 (DM1) locus and the interaction with RNA CUG-binding proteins
-
A second point is that DM mutations, although located in noncoding regions, may reduce the expression of mutant alleles, raising questions whether loss-of-function may contribute to the phenotype, or possibly impose a safety limit on knockdown therapies that create or aggravate a DMPK or CNBP deficiency state
-
(CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations of Malaysia were discovered.
-
The patients with DM1 nucleotide expansion (CTG) mutation showed widespread abnormalities of all DTI parameters in the white matter, which were associated with reduced gray matter volume in all brain lobes and thinning in parieto-temporo-occipital cortices.
-
Our work suggests that DM1 patients are at risk for Fuchs' endothelial corneal dystrophy (FECD). DMPK mutations contribute to the genetic burden of FECD but are uncommon. We establish a connection between two repeat expansion disorders converging upon RNA-MBNL1 foci and FECD.
-
findings thus suggest that nuclear retention may be a common feature of regulation of DMPK RNA expression. The typical forced nuclear residence of expanded DMPK transcripts affects this regulation in tissues of DM1 patients, but not through hyperadenylation.
-
Data, including data from studies on synthetic RNA modeling RNA repeat expansions found in patients with Huntington's disease (mRNA for exon 1 of Huntingtin protein) and myotonic dystrophy type 1 (mRNA for 3prime untranslated region of dystrophia myotonica-protein kinase), suggest internal loops of r(3xCAG) are stabilized by one-hydrogen bond AA pairs, while those of r(3xCUG) prefer one- or two-hydrogen bond UU pairs.
-
Analysis of five intergenerational transmissions revealed a substantial intrafamilial stability of the DM1 mutation among relatives.
-
Methylation upstream of the expanded DMPK CTG repeat occurs exclusively with maternal transmission and that it is somehow linked to the development of congenital myotonic dystrophy.
-
Study shows DMPK expression with a complex pattern of tissue-specific epigenetics consistent with evidence that normal tissue require careful regulation of its RNA and protein levels which might include cis-acting regulatory elements in neighboring genes.
-
Sense DMPK RNA foci clearly co-localize with MBNL1 and MBNL2 proteins and accumulate in myotonic dystrophy 1 tissues during development.
-
This study supports the idea that genetic abnormalities in DM1mainly target the white matter, but gray matter involvement is also crucial in determining the clinical characteristics of myotonic dystrophy type 1.