scholarly journals Syncope and hyperCKemia as minimal manifestations of short CTG repeat expansions in myotonic dystrophy type 1

2015 ◽  
Vol 34 (5) ◽  
pp. 361.e1-361.e4
Author(s):  
Josef Finsterer ◽  
Claudia Stöllberger ◽  
Martin Gencik ◽  
Romana Höftberger ◽  
Jasmin Rahimi ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Repeat Expansions ◽  
Ctg Repeat

scholarly journals Novel Heat Pulse Extension-PCR–Based Method for Detection of Large CTG-Repeat Expansions in Myotonic Dystrophy Type 1

2013 ◽  
Vol 15 (1) ◽  
pp. 110-115 ◽  
Author(s):  
Arto K. Orpana ◽  
Tho H. Ho ◽  
Katariina Alagrund ◽  
Maaret Ridanpää ◽  
Kristiina Aittomäki ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Heat Pulse ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Repeat Expansions ◽  
Ctg Repeat

scholarly journals Syncope and hyperCKemia as minimal manifestations of short CTG repeat expansions in myotonic dystrophy type 1

2015 ◽  
Vol 34 (5) ◽  
pp. 361.e1-361.e4 ◽  
Author(s):  
Josef Finsterer ◽  
Claudia Stöllberger ◽  
Martin Gencik ◽  
Romana Höftberger ◽  
Jasmin Rahimi ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Repeat Expansions ◽  
Ctg Repeat

scholarly journals High Throughput Screening for Expanded CTG repeats in Myotonic Dystrophy Type 1 Using Melt Curve Analysis

2021 ◽  
Author(s):  
Russell J Butterfield ◽  
Carina Imburgia ◽  
Katie Mayne ◽  
Tara Newcomb ◽  
Diane M Dunn ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
High Throughput ◽  
Curve Analysis ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Melt Curve Analysis ◽  
Ctg Repeats ◽  
Repeat Expansions ◽  
Ctg Repeat

ABSTRACTBackgroundMyotonic dystrophy type 1 (DM1) is caused by CTG repeat expansions in the DMPK gene and is the most common form of muscular dystrophy. Patients can have long delays from onset to diagnosis, since clinical signs and symptoms are often non-specific and overlapping with other disorders. Clinical genetic testing by Southern blot or triplet-primed PCR (TP-PCR) is technically challenging and cost prohibitive for population surveys.MethodsHere, we present a high throughput, low-cost screening tool for CTG repeat expansions using TP-PCR followed by high resolution melt curve analysis with saturating concentrations of SYBR GreenER dye.ResultsWe determined that multimodal melt profiles from the TP-PCR assay are a proxy for amplicon length stoichiometry. In a screen of 10,097 newborn blood spots, melt profile analysis accurately reflected the tri-modal distribution of common alleles from 5 to 35 CTG repeats, and identified the premutation and full expansion alleles.ConclusionWe demonstrate that robust detection of expanded CTG repeats in a single tube can be achieved from samples derived from specimens with minimal template DNA such as dried blood spots (DBS). This technique is readily adaptable to large-scale testing programs such as population studies and newborn screening programs.

scholarly journals CTG-Repeat Detection in Primary Human Myoblasts of Myotonic Dystrophy Type 1

2021 ◽  
Vol 15 ◽  
Author(s):  
Stefan Hintze ◽  
Raphaela Mensel ◽  
Lisa Knaier ◽  
Benedikt Schoser ◽  
Peter Meinke
Keyword(s):  
Myotonic Dystrophy ◽  
Muscle Biopsy ◽  
Biopsy Specimen ◽  
Repeat Length ◽  
Model Systems ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Repeat Expansions ◽  
Ctg Repeat

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by unstable CTG-repeat expansions in the DMPK gene. Tissue mosaicism has been described for the length of these repeat expansions. The most obvious affected tissue is skeletal muscle, making it the first target for therapy development. To date there is no approved therapy despite some existing approaches. Thus, there is the demand to further advance therapeutic developments, which will in return require several well-characterized preclinical tools and model systems. Here we describe a modified method to identify the CTG-repeat length in primary human myoblasts isolated from DM1 patients that requires less genomic DNA and avoids radioactive labeling. Using this method, we show that primary human DM1 myoblast cultures represent a population of cells with different CTG-repeat length. Comparing DNA from the identical muscle biopsy specimen, the range of CTG-repeat length in the myoblast culture is within the same range of the muscle biopsy specimen. In conclusion, primary human DM1 myoblast cultures are a well-suited model to investigate certain aspects of the DM1 pathology. They are a useful platform to perform first-line investigations of preclinical therapies.

Origin of the myotonic dystrophy type 1 mutation in Mexican population and influence of Amerindian ancestry on CTG repeat allelic distribution

2017 ◽  
Vol 27 (12) ◽  
pp. 1106-1114 ◽  
Author(s):  
N.M. Murillo-Melo ◽  
L.C. Márquez-Quiróz ◽  
R. Gómez ◽  
L. Orozco ◽  
E. Mendoza-Caamal ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Mexican Population ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Allelic Distribution ◽  
Ctg Repeat

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1

Neurology ◽  
2004 ◽  
Vol 62 (7) ◽  
pp. 1081-1089 ◽  
Author(s):  
E. L. Logigian ◽  
R. T. Moxley ◽  
C. L. Blood ◽  
C. A. Barbieri ◽  
W. B. Martens ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Length ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeat

scholarly journals MSH2 knock-down shows CTG repeat stability and concomitant upstream demethylation at the DMPK locus in myotonic dystrophy type 1 human embryonic stem cells

2020 ◽  
Author(s):  
Silvie Franck ◽  
Lise Barbé ◽  
Simon Ardui ◽  
Yannick De Vlaeminck ◽  
Joke Allemeersch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Myotonic Dystrophy ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cpg Methylation ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeat

Abstract Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the DMPK gene, where expansion size and somatic mosaicism correlates with disease severity and age of onset. While it is known that the mismatch repair protein MSH2 contributes to the unstable nature of the repeat, its role on other disease-related features, such as CpG methylation upstream of the repeat, is unknown. In this study, we investigated the effect of an MSH2 knock-down (MSH2KD) on both CTG repeat dynamics and CpG methylation pattern in human embryonic stem cells (hESC) carrying the DM1 mutation. Repeat size in MSH2 wild type (MSH2WT) and MSH2KD DM1 hESC was determined by PacBio sequencing and CpG methylation by bisulfite massive parallel sequencing. We found stabilization of the CTG repeat concurrent with a gradual loss of methylation upstream of the repeat in MSH2KD cells, while the repeat continued to expand and upstream methylation remained unchanged in MSH2WT control lines. Repeat instability was re-established and biased towards expansions upon MSH2 transgenic re-expression in MSH2KD lines while upstream methylation was not consistently re-established. We hypothesize that the hypermethylation at the mutant DM1 locus is promoted by the MMR machinery and sustained by a constant DNA repair response, establishing a potential mechanistic link between CTG repeat instability and upstream CpG methylation. Our work represents a first step towards understanding how epigenetic alterations and repair pathways connect and contribute to the DM1 pathology.

scholarly journals Structure and Dynamics of RNA Repeat Expansions That Cause Huntington’s Disease and Myotonic Dystrophy Type 1

Biochemistry ◽  
2017 ◽  
Vol 56 (27) ◽  
pp. 3463-3474 ◽  
Author(s):  
Jonathan L. Chen ◽  
Damian M. VanEtten ◽  
Matthew A. Fountain ◽  
Ilyas Yildirim ◽  
Matthew D. Disney
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Structure And Dynamics ◽  
Repeat Expansions
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