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RNA repeat expansions cause a host of incurable, genetically-defined diseases. The most common class of RNA repeats are trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs while those of r(3×CUG) prefer one or two hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form, and that the loop regions are dynamic. The results will be useful to understand the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.
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Identifying large expansions of short tandem repeats (STRs) such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome is challenging for short-read whole-genome sequencing (W...
Different oculomotor abnormalities have been reported to occur in premanifest Huntington's disease. The aim of this study is to investigate which oculomotor items of the Unified Huntington's Disease R...
Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington's disease. Because expansions trigger t...
Expansions of microsatellite repeats are responsible for numerous hereditary diseases in humans, including myotonic dystrophy and Friedreich's ataxia. Whereas the length of an expandable repeat is the...
In 1999, a polyglutamine expansion was identified in the transcription factor TATA-binding protein (TBP) in a patient with ataxia with negative family history. Subsequently, CAG/CAA repeat expansions ...
The purpose of this trial is to study early brain and behavioral changes in people who have the gene expansion for Huntington's disease, but are currently healthy and have no symptoms.
This study is being conducted to determine the safety and tolerability of Dimebon in people with Huntington's disease after short-term exposure (one week) and after longer exposure (three ...
The purpose of this study is to know the limits of feasibility of a reliable oculomotor record for patient with Huntington's disease.
The purpose of this study is to define the natural history and experiences of people who are at risk for developing Huntington's disease but who do not know their genetic status.
The purpose of the study is to collect and assess long term data on the safety, tolerability, and efficacy of pridopidine in patients with Huntington's disease (HD).
Membrane glycosylphosphatidylinositol-anchored glycoproteins that may aggregate into rod-like structures. The prion protein (PRNP) gene is characterized by five TANDEM REPEAT SEQUENCES that encode a highly unstable protein region of five octapeptide repeats. Mutations in the repeat region and elsewhere in this gene are associated with CREUTZFELDT-JAKOB DISEASE; FATAL FAMILIAL INSOMNIA; GERSTMANN-STRAUSSLER DISEASE; Huntington disease-like 1, and KURU.
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION, POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.
A protein that is highly expressed in the nervous system as well as other tissues; its size and structure vary due to polymorphisms. Expanded CAG TRINUCLEOTIDE REPEATS have been identified in the Huntingtin (HD) Gene of patients with HUNTINGTON DISEASE and are associated with abnormal PROTEIN AGGREGATES. Huntingtin interacts with proteins involved in a variety of gene expression and cellular processes; it is also essential for embryonic development.
A spectrum of disorders characterized by clonal expansions of the peripheral blood LYMPHOCYTE populations known as large granular lymphocytes which contain abundant cytoplasm and azurophilic granules. Subtypes develop from either CD3-negative NATURAL KILLER CELLS or CD3-positive T-CELLS. The clinical course of both subtypes can vary from spontaneous regression to progressive, malignant disease.
A repeat operation for the same condition in the same patient due to disease progression or recurrence, or as followup to failed previous surgery.
Huntington's disease is a hereditary disease caused by a defect in a single gene on Chromosome 4 that is inherited in an autosomal dominant fashion. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to...
Muscular dystrophy is a group of degenerative inherited disorders causing muscle weakness and loss of muscle tissue. The different types are Becker muscular dystrophy, Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, Facioscapulohumeral mu...