scholarly journals Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity

2012 ◽  
Vol 21 (16) ◽  
pp. 3558-3567 ◽  
Author(s):  
Fernando Morales ◽  
Jillian M. Couto ◽  
Catherine F. Higham ◽  
Grant Hogg ◽  
Patricia Cuenca ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Disease Severity ◽  
Quantitative Trait ◽  
Triplet Repeat ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Somatic Instability ◽  
Ctg Triplet Repeat

Myotonic dystrophy type 1 (DM1): A triplet repeat expansion disorder

Gene ◽  
2013 ◽  
Vol 522 (2) ◽  
pp. 226-230 ◽  
Author(s):  
Ashok Kumar ◽  
Sarita Agarwal ◽  
Divya Agarwal ◽  
Shubha R. Phadke
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Expansion ◽  
Triplet Repeat ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Triplet Repeat Expansion

Somatic instability of CTG repeats in the cerebellum of myotonic dystrophy type 1

2013 ◽  
Vol 48 (1) ◽  
pp. 105-108 ◽  
Author(s):  
Kenji Jinnai ◽  
Maki Mitani ◽  
Naonobu Futamura ◽  
Kunihiko Kawamoto ◽  
Itaru Funakawa ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeats ◽  
Somatic Instability

scholarly journals The Myotonic Dystrophy Type 1 Triplet Repeat Sequence Induces Gross Deletions and Inversions

2004 ◽  
Vol 280 (2) ◽  
pp. 941-952 ◽  
Author(s):  
Marzena Wojciechowska ◽  
Albino Bacolla ◽  
Jacquelynn E. Larson ◽  
Robert D. Wells
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Sequence ◽  
Triplet Repeat ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

scholarly journals Structure of an RNA helix with pyrimidine mismatches and cross-strand stacking

2019 ◽  
Vol 75 (10) ◽  
pp. 652-656 ◽  
Author(s):  
Eric J. Montemayor ◽  
Johanna M. Virta ◽  
Lauren D. Hagler ◽  
Steven C. Zimmerman ◽  
Samuel E. Butcher
Keyword(s):  
Myotonic Dystrophy ◽  
Base Pair ◽  
Structural Diversity ◽  
Triplet Repeat ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Base Pairs ◽  
Pyrimidine Base ◽  
High Degree

The structure of a 22-base-pair RNA helix with mismatched pyrimidine base pairs is reported. The helix contains two symmetry-related CUG sequences: a triplet-repeat motif implicated in myotonic dystrophy type 1. The CUG repeat contains a U–U mismatch sandwiched between Watson–Crick pairs. Additionally, the center of the helix contains a dimerized UUCG motif with tandem pyrimidine (U–C/C–U) mismatches flanked by U–G wobble pairs. This region of the structure is significantly different from previously observed structures that share the same sequence and neighboring base pairs. The tandem pyrimidine mismatches are unusual and display sheared, cross-strand stacking geometries that locally constrict the helical width, a type of stacking previously associated with purines in internal loops. Thus, pyrimidine-rich regions of RNA have a high degree of structural diversity.

scholarly journals Genetic determinants of disease severity in the myotonic dystrophy type 1 OPTIMISTIC cohort

Neurology ◽  
2019 ◽  
Vol 93 (10) ◽  
pp. e995-e1009 ◽  
Author(s):  
Sarah A. Cumming ◽  
Cecilia Jimenez-Moreno ◽  
Kees Okkersen ◽  
Stephan Wenninger ◽  
Ferroudja Daidj ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Disease Severity ◽  
Target Identification ◽  
Age At Onset ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Specific Outcome ◽  
Allele Length ◽  
Ctg Repeat

ObjectiveTo evaluate the role of genetic variation at the DMPK locus on symptomatic diversity in 250 adult, ambulant patients with myotonic dystrophy type 1 (DM1) recruited to the Observational Prolonged Trial in Myotonic Dystrophy Type 1 to Improve Quality of Life—Standards, a Target Identification Collaboration (OPTIMISTIC) clinical trial.MethodsWe used small pool PCR to correct age at sampling biases and estimate the progenitor allele CTG repeat length and somatic mutational dynamics, and AciI digests and repeat primed PCR to test for the presence of variant repeats.ResultsWe confirmed disease severity is driven by progenitor allele length, is further modified by age, and, in some cases, sex, and that patients in whom the CTG repeat expands more rapidly in the soma develop symptoms earlier than predicted. We revealed a key role for variant repeats in reducing disease severity and quantified their role in delaying age at onset by approximately 13.2 years (95% confidence interval 5.7–20.7, 2-tailed t test t = −3.7, p = 0.0019).ConclusionsCareful characterization of the DMPK CTG repeat to define progenitor allele length and presence of variant repeats has increased utility in understanding clinical variability in a trial cohort and provides a genetic route for defining disease-specific outcome measures, and the basis of treatment response and stratification in DM1 trials.

MBNL1 gene variants as modifiers of disease severity in myotonic dystrophy type 1

2012 ◽  
Vol 260 (4) ◽  
pp. 998-1003 ◽  
Author(s):  
Vincent Huin ◽  
Francis Vasseur ◽  
Susanna Schraen-Maschke ◽  
Claire-Marie Dhaenens ◽  
Patrick Devos ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Disease Severity ◽  
Gene Variants ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type
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