Oculopharyngeal muscular dystrophy
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Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing Open
The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encodi…
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Correlation between <i>PABPN1</i> genotype and disease severity in oculopharyngeal muscular dystrophy Open
It has been difficult to establish phenotype-genotype correlations because of the rare nature of this disease. Our work demonstrates that patients with OPMD with longer PABPN1 expansion are on average diagnosed at an earlier age than patie…
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Recent Progress in Oculopharyngeal Muscular Dystrophy Open
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset intractable myopathy, characterized by slowly progressive ptosis, dysphagia, and proximal limb weakness. It is caused by the abnormal expansion of the alanine-encoding (GCN)n trinuc…
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Clinicopathologic Features of Oculopharyngodistal Myopathy With<i>LRP12</i>CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes Open
This study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle bi…
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Novel mouse models of oculopharyngeal muscular dystrophy (OPMD) reveal early onset mitochondrial defects and suggest loss of PABPN1 may contribute to pathology Open
Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease caused by polyalanine expansion in the poly(A) binding protein nuclear 1 (PABPN1). Several mouse models have been generated to study OPMD; however, most of these models have…
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Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy Open
Background and objective Oculopharyngeal muscular dystrophy (OPMD) is a genetic disorder caused by an abnormal expansion of GCN triplets within the PABPN1 gene. Previous descriptions have focused on lower limb muscles in small cohorts of p…
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PABPN1-Dependent mRNA Processing Induces Muscle Wasting Open
Poly(A) Binding Protein Nuclear 1 (PABPN1) is a multifunctional regulator of mRNA processing, and its expression levels specifically decline in aging muscles. An expansion mutation in PABPN1 is the genetic cause of oculopharyngeal muscle d…
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Dysphagia‐related quality of life in oculopharyngeal muscular dystrophy: Psychometric properties of the SWAL‐QOL instrument Open
Introduction The Swallowing Quality of Life instrument (SWAL‐QOL) is a patient‐reported outcome measure of swallowing‐related quality of life (SR‐QoL). Its psychometric properties in oculopharyngeal muscular dystrophy (OPMD) are not known.…
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Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD) Open
Background Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset muscle disease affecting one per 80 000 of the general population characterized by profound dysphagia and ptosis, and limb weakness at later stages. Affected muscles are …
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Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing Open
A short abnormal polyalanine expansion in the polyadenylate-binding protein nuclear-1 (PABPN1) protein causes oculopharyngeal muscular dystrophy (OPMD). Mutated PABPN1 proteins accumulate as insoluble intranuclear aggregates in muscles of …
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Trinucleotide CGG Repeat Diseases: An Expanding Field of Polyglycine Proteins? Open
Microsatellites are repeated DNA sequences of 3–6 nucleotides highly variable in length and sequence and that have important roles in genomes regulation and evolution. However, expansion of a subset of these microsatellites over a threshol…
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Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy Open
Oculopharyngeal muscular dystrophy (OPMD) is a rare late onset genetic disease leading to ptosis, dysphagia and proximal limb muscles at later stages. A short abnormal (GCN) triplet expansion in the polyA-binding protein nuclear 1 (PABPN1)…
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Oropharyngeal dysphagia profiles in individuals with oculopharyngeal muscular dystrophy Open
Background Although dysphagia represents a hallmark manifestation of oculopharyngeal muscular dystrophy ( OPMD ), limited knowledge exists regarding the underlying nature of oropharyngeal swallowing impairments in this patient population. …
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Multilingual website and cyberconsultations for oromandibular dystonia Open
Oromandibular dystonia is a focal dystonia that manifests as involuntary masticatory and/or tongue muscle contractions. This movement disorder is frequently misdiagnosed as a temporomandibular disorder. Hence, it would be useful to establi…
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Diagnostics of short tandem repeat expansion variants using massively parallel sequencing and componential tools Open
Short tandem repeats (STRs) are scattered throughout the human genome. Some STRs, like trinucleotide repeat expansion (TRE) variants, cause hereditable disorders. Unambiguous molecular diagnostics of TRE disorders is hampered by current te…
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RNA-Based Therapy Utilizing Oculopharyngeal Muscular Dystrophy Transcript Knockdown and Replacement Open
Oculopharyngeal muscular dystrophy (OPMD) is caused by a small expansion of a short polyalanine (polyAla) tract in the poly(A)-binding protein nuclear 1 protein (PABPN1). Despite the monogenic nature of OPMD, no treatment is currently avai…
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Longitudinal Assessment of Strength, Functional Capacity, Oropharyngeal Function, and Quality of Life in Oculopharyngeal Muscular Dystrophy Open
Despite the slow disease progression of OPMD, this study showed that several outcome measures detected progression within 20 months. Deltoid muscle strength, measured by fixed dynamometry, showed the greatest decline. These longitudinal da…
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Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR Open
RNA processing is critical for proper spatial and temporal control of gene expression. The ubiquitous nuclear polyadenosine RNA binding protein, PABPN1, post-transcriptionally regulates multiple steps of gene expression. Mutations in the P…
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Assessment of PABPN1 nuclear inclusions on a large cohort of patients and in a human xenograft model of oculopharyngeal muscular dystrophy Open
Oculopharyngeal muscular dystrophy (OPMD) is a rare muscle disease characterized by an onset of weakness in the pharyngeal and eyelid muscles. The disease is caused by the extension of a polyalanine tract in the Poly(A) Binding Protein Nuc…
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Swallowing, Chewing and Speaking: Frequently Impaired in Oculopharyngeal Muscular Dystrophy Open
Background: Oculopharyngeal muscular dystrophy (OPMD) is a late onset progressive neuromuscular disorder. Although dysphagia is a pivotal sign in OPMD it is still not completely understood. Objective: The aim of this study was to systemati…
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Dysfunctional transcripts are formed by alternative polyadenylation in OPMD Open
Post-transcription mRNA processing in the 3'-untranslated region (UTR) of transcripts alters mRNA landscape. Alternative polyadenylation (APA) utilization in the 3'-UTR often leads to shorter 3'-UTR affecting mRNA stability, a process that…
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Value of insoluble PABPN1 accumulation in the diagnosis of oculopharyngeal muscular dystrophy Open
Background and purpose The aim was to assess the value of insoluble PABPN1 muscle fibre nuclei accumulation in the diagnosis of atypical cases of oculopharyngeal muscular dystrophy (OPMD). Methods Muscle biopsies from a selected cohort of …
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Frequency and type of cancers in myotonic dystrophy: A retrospective cross‐sectional study Open
Introduction/Aims Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem invol…
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Established PABPN1 intranuclear inclusions in OPMD muscle can be efficiently reversed by AAV-mediated knockdown and replacement of mutant expanded PABPN1 Open
Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant late-onset muscular dystrophy affecting approximately 1:100 000 individuals in Europe. OPMD is mainly characterized by progressive eyelid drooping (ptosis) and dysphagi…
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Late-onset myopathies: clinical features and diagnosis. Open
Late-onset myopathies are not well-defined since there is no clear definition of 'late onset'. For practical reasons we decided to use the age of 40 years as a cut-off. There are diseases which only manifest as late onset myopathy (inclusi…
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Efficacy of Botulinum Toxin for Treating Sialorrhea in Neuromuscular Conditions Open
Background: Drooling related to bulbar weakness and dysfunction is a common concern in patients with neuromuscular disease. While there are numerous medications to manage sialorrhea, they are often limited by side effects and lack of effic…
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Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy Open
Small non-coding microRNAs (miRNAs) are involved in the regulation of mRNA stability. Their features, including high stability and secretion to biofluids, make them attractive as potential biomarkers for diverse pathologies. This is the fi…
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Differential diagnosis of vacuolar muscle biopsies: use of p62, LC3 and LAMP2 immunohistochemistry. Open
Intrafibral vacuoles are the morphological hallmark in a wide variety of human skeletal muscle disorders with different etiology. In most cases, differential diagnosis is feasible with a routine histochemical work up of muscle biopsy. Ultr…
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Fourier-Transform Infrared Spectroscopy of Skeletal Muscle Tissue: Expanding Biomarkers in Primary Mitochondrial Myopathies Open
Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform…
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Valproic acid is protective in cellular and worm models of oculopharyngeal muscular dystrophy Open
Our results suggest that VPA helps to counteract OPMD-related phenotypes in the cellular and C elegans disease models.