scholarly journals Congenital Phenotypes and DMPK CTG Repeat Number in Mothers and Children With Myotonic Dystrophy Type 1

2021 ◽  
Author(s):  
Kosuke Shigematsu ◽  
Yukiko Mikami ◽  
Yasushi Takai ◽  
Haipeng Huang ◽  
Mamiko Shinsaka ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Sequence ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Repeat Number ◽  
Congenital Myotonic Dystrophy ◽  
Mother And Child ◽  
The Mean ◽  
Ctg Repeat

Abstract Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease. In DM1, the mutant allele expands during gametogenesis, and an extended CTG repeat sequence is inherited by the offspring. This often results in increased severity of DM1 symptoms in the affected offspring and may cause congenital myotonic dystrophy (CDM). This study aimed to clarify whether CTG repeat number predicts CDM in offspring. This retrospective study examined 14 women with DM1, their pregnancy and labor histories, and their 14 children diagnosed with DM1. There were 12 CDM patients and 2 non-CDM patients. Correlations between CDM onset and CTG repeat numbers of the mother and child were analyzed. Women who bore a child with CDM (infants with detected polyhydramnios during pregnancy, hypotonia, respiratory insufficiency, or suckling failure at birth) had a mean repeat number of 643 (standard deviation [SD] 436). For women who bore a child without CDM, the mean repeat number was 950 (SD 71), and no significant between-group difference was detected. The mean (SD) CTG repeat numbers observed in children with and without CDM were 1,646 (324) and 1,700 (565), respectively. CDM cannot be predicted based on the CTG repeat numbers of mothers or children.

SEVERE CONGENITAL MYOTONIC DYSTROPHY TYPE 1

2018 ◽  
Vol 97 (1) ◽  
pp. 78-81
Author(s):  
E.A. Mamaeva ◽  
◽  
L.A. Fedorova ◽  
S.E. Voronovich ◽  
V.D. Nazarov ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Congenital Myotonic Dystrophy

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 Stable Longitudinal Methylation Levels at the CpG Sites Flanking the CTG Repeat of DMPK in Patients with Myotonic Dystrophy Type 1

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 936
Author(s):  
Mathis Hildonen ◽  
Kirsten Lykke Knak ◽  
Morten Dunø ◽  
John Vissing ◽  
Zeynep Tümer
Keyword(s):  
Myotonic Dystrophy ◽  
Autosomal Dominant ◽  
Maternal Inheritance ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Muscle Loss ◽  
Multisystem Disorder ◽  
Ctg Repeat ◽  
Over Time

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder mainly characterized by gradual muscle loss, weakness, and delayed relaxation after muscle contraction. It is caused by an expanded CTG repeat in the 3′ UTR of DMPK, which is transcribed into a toxic gain-of-function mRNA that affects the splicing of a range of other genes. The repeat is unstable, with a bias towards expansions both in somatic cells and in the germline, which results in a tendency for earlier onset with each generation, as longer repeat lengths generally correlate with earlier onset. Previous studies have found hypermethylation in the regions flanking the repeat in congenital onset DM1 and in some patients with non-congenital DM1. We used pyrosequencing to investigate blood methylation levels in 68 patients with non-congenital DM1, compare the methylation levels between the blood and muscle, and assess whether methylation levels change over time in the blood. We found higher methylation levels in the blood of DM1 patients than in healthy controls and especially in the patients who had inherited the disease allele maternally. The methylation levels remained relatively stable over time and are a strong biomarker of the disease, as well as of the maternal inheritance of the disease.

scholarly journals Replacement of the myotonic dystrophy type 1 CTG repeat with 'non-CTG repeat' insertions in specific tissues

2011 ◽  
Vol 48 (7) ◽  
pp. 438-443 ◽  
Author(s):  
M. M. Axford ◽  
A. Lopez-Castel ◽  
M. Nakamori ◽  
C. A. Thornton ◽  
C. E. Pearson
Keyword(s):  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeat

Stapedial reflex in myotonic dystrophy type 1 and CTG repeat expansion

2001 ◽  
Vol 248 (12) ◽  
pp. 1056-1061 ◽  
Author(s):  
Ryuichi Osanai ◽  
Masanobu Kinoshita ◽  
Kazuhiko Hirose
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Expansion ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Stapedial Reflex ◽  
Ctg Repeat
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