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Structure and Dynamics of DNA and RNA Double Helices Formed by d(CTG), d(GTC), r(CUG), and r(GUC) Trinucleotide Repeats and Associated DNA-RNA Hybrids.

Myotonic dystrophy type 1 is the most frequent form of muscular dystrophy in adults caused by an abnormal expansion of the CTG trinucleotide. Both the expanded DNA and the expanded CUG RNA transcript can fold into hairpins. Co-transcriptional formation of stable RNA·DNA hybrids can also enhance the instability of repeat tracts. We performed molecular dynamics simulations of homoduplexes associated with the disease, d(CTG)n and r(CUG)n, and their corresponding r(CAG)n:d(CTG)n and r(CUG)n:d(CAG)n hybrids that can form under bidirectional transcription and of non-pathological d(GTC)n and d(GUC)n …

Best practice recommendations for speech-language pathology in children with neuromuscular disorders: A Delphi-based consensus study.

PURPOSE: Speech-language pathology (SLP) is considered an essential intervention due to the high prevalence of dysphagia and dysarthria in p … tervention items for cases of four types of pNMD (congenital myopathy, Duchenne muscular dystrophy, myotonic dystrophy type 1, and spinal muscular atrophy type 2), covering symptoms of dysphagia, dysarthria, drooling, and oral hygiene problems. They rated the level of agreement. RESULT: Intervention items that achieved consensus were incorporated into best practice …

Distribution of alternative untranslated regions within the mRNA of the CELF1 splicing factor affects its expression.

CUG-binding protein, ELAV-like Family Member 1 (CELF1) plays an important role during the development of different tissues, such as striated muscle and brain tissue. CELF1 is an RNA-binding protein that regulates RNA metabolism processes, e.g., alternative splicing, and antagonizes other RNA-binding proteins, such as Muscleblind-like proteins (MBNLs). Abnormal activity of both classes of proteins plays a crucial role in the pathogenesis of myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults. In this work, we show that alternative splicing of exons forming both…

[Erythrocyte from Duchenne muscular dystrophy is fragile].

Intermittent indirect hyperbilirubinemia was occasionally observed in Duchenne muscular dystrophy (DMD) patients. We suspected that hyperbilirubinemia might be caused by hemolysis of fragile erythrocytes due to damaged endothelium, which was reported in DMD. To examine the fragility of erythrocytes, we performed osmotic resistance test in 25 DMD, 12 myotonic dystrophy (DM), 12 amyotrophic lateral sclerosis (ALS) and 24 healthy volunteers (male 15, female 9). Minimum resistance (beginning point of hemolysis) of DMD (0.447 +/- 0.016%) was higher than that of age matched male controls (0.425 +/- …

Strength training and aerobic exercise training for muscle disease.

BACKGROUND: Strength training or aerobic exercise programmes, or both, might optimise muscle and cardiorespiratory function and prevent addi … FSHD), dermatomyositis, polymyositis, mitochondrial myopathy, Duchenne muscular dystrophy (DMD), or myotonic dystrophy. Risk of bias was variable, as blinding of participants was not possible, some trials did not blind outcome assessors, and some did not use an intention-to-treat analysis. Strength training compared to no training (3 trials) For participants with FS …

Orthopaedic abnormalities in primary myopathies.

Orthopaedic abnormalities are frequently recognised in patients with myopathy but are hardly systematically reviewed with regard to type of myopathy, type of orthopaedic problem, and orthopaedic management. This review aims to summarize recent findings and current knowledge about orthopaedic abnormalities in these patients, their frequency, and possible therapeutic interventions. A MEDLINE search for the combination of specific terms was carried out and appropriate articles were reviewed for the type of myopathy, types of orthopaedic abnormalities, frequency of orthopaedic abnormalities, and p

Analysis of Trinucleotide Repeat Stability by Integration at a Chromosomal Ectopic Site.

Expansions of CNG microsatellite tracts are responsible for several neurodegenerative diseases, including myotonic dystrophy type 1, Huntington disease, and spinocerebellar ataxia type 8. Here we show that expanded (CNG)n repeats are susceptible not only to expansions and contractions, but are prone to DNA double strand breaks following replication stress. We describe a general strategy for the construction of clonal cell lines containing CNG repeats of various lengths, in which the microsatellites are integrated using the yeast FLP recombinase at a single ectopic recombination acceptor site i…

DNA triplet repeat expansion and mismatch repair.

DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the exp…

Idiopathic isolated orbicularis weakness.

PURPOSE: Orbicularis weakness is commonly associated with seventh nerve palsy or neuromuscular and myopathic conditions such as myotonic dystrophy and myasethenia gravis. We report four cases of idiopathic isolated orbicularis weakness. METHODS: All four cases were female and the presenting symptoms of ocular irritation and epiphora had been present for over 7 years in three patients. All patients had lagophthalmos and three had ectropion. Three patients underwent full investigations which excluded known causes of orbicularis weakness. Two patients underwent oribularis oculi muscle biopsy and…

Mosaicism in Short Tandem Repeat Disorders: A Clinical Perspective.

Fragile X, Huntington disease, and myotonic dystrophy type 1 are prototypical examples of human disorders caused by short tandem repeat variation, repetitive nucleotide stretches that are highly mutable both in the germline and somatic tissue. As short tandem repeats are unstable, they can expand, contract, and acquire and lose epigenetic marks in somatic tissue. This means within an individual, the genotype and epigenetic state at these loci can vary considerably from cell to cell. This somatic mosaicism may play a key role in clinical pathogenesis, and yet, our understanding of mosaicism in …

Cholesterol Management in Neurology: Time for Revised Strategies?

Statin therapy has been extensively evaluated and shown to reduce the incidence of new or recurrent vascular events, ischemic stroke include … tment, and whose age and cholesterol levels put them at risk for ischemic stroke; (3) patients with myotonic dystrophy, whose disease often associates diabetes mellitus and heart conduction defects, and in whom blood cholesterol management is also not settled. As such, further trials are needed to address these issues.

Detection of large expansions in SCA8 using a fluorescent repeat-primed PCR assay.

Spinocerebellar ataxia type 8 (SCA8) is a neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. It is caused by bidirectional expression of (CUG)n expansion in the ATXN80S/ATXN8 gene and (CAG)n expansion transcripts in ATXN8. The diagnosis of SCA8 must be confirmed by the presence of a (CTG)n trinucleotide repeat expansion in the ATXN8OS gene. On the other hand, there are many human genetic diseases that are caused by expansion of short tandem repeats. Since Werner et al proposed a repeat-primed fluorescent PCR to detect large CTG-repeats in myotonic dystrophy, Frie…

CTG repeats at the myotonic protein kinase gene in a healthy Chilean population sample.

OBJECTIVES: To study the variability at the myotonic dystrophy protein kinase (DMPK) gene in a Chilean sample of healthy people. DM1 is an autosomal dominant disorder caused by an expansion of a (CTG) repeat at the 3'-UTR of the gene DMPK. Healthy individuals have alleles under 35 repeats and diseased individuals have over 50. METHODS: Genotyping the number of (CTG) repeats at this gene in a sample of healthy Chilean people. RESULTS: Allele frequencies were significantly different from those of other populations. The most frequent allele was with five repeats. The frequency of larger alleles…

[Aldolase].

Aldolase (EC 4.1.2.13) plays an important role in glucose metabolism. Aldolase has a molecular weight of 160 kDa and has three isozymes, namely aldolase A, B and C. The enzyme is probably present in all cells; it occurs in particularly large quantities in the muscles, liver and brain. An increase in serum aldolase is found in myotonic muscular disease, such as progressive muscular dystrophy and polymyositis. The enzyme rises in myocardial infarction, reaches a maximum within 24-48 hours and returns to normal in the course of five days. In these muscular diseases, aldolase A isozyme is elevated

Double discharges in neuromuscular diseases.

Double discharges (doublets) of motor units were examined in routine EMG. The material consisted of 132 patients suffering from different neuromuscular diseases and 34 controls in whom the examined muscles were intact. Only m. tibialis anterior and biceps brachii were examined. Activity from at least 10 different motor units per muscle were recorded and analyzed off-line. Modified criteria were used in determining doubling units. Applying the modified criteria no doubling units were found in controls. In myopathies doublets occurred only in myotonic dystrophy and in one case of polymyositis in…

Subclinical cardiac involvement present as electrocardiographic abnormalities in various neuromuscular diseases.

BACKGROUND: Cardiac involvement is commonly present in various neuromuscular diseases which may develop life-threatening consequences. The early manifestation is often asymptomatic which however has been insufficiently studied. OBJECTIVES: We aim to characterize electrocardiographic (ECG) changes in neuromuscular diseases without cardiac symptoms. METHODS: Adults having genetically and/or pathologically confirmed type 1 myotonic dystrophy (DM1), Becker muscular dystrophy (BMD), limb girdle muscular dystrophies (LGMDs) and mitochondrial diseases (MtDs) but without history of heart diseases an…

Overview of Neuromuscular Disorder Molecular Diagnostic Experience for the Population of Latvia.

BACKGROUND AND OBJECTIVES: Genetic testing has become an integral part of health care, allowing the confirmation of thousands of hereditary … enital myotonia, 0.052 per 10,000 for spinobulbar muscular atrophy, and 0.047 per 10,000 for type 1 myotonic dystrophy. DISCUSSION: DNA diagnostics is a successful approach. The carrier frequencies of the common CAPN3, FKRP, SPG11, and HINT1 gene variants as well as that of the SMN1 gene exon 7 deletion in the population of Latvia are comparable with data from Euro …

Electric and CO2 laser SEPs in a patient with asymptomatic syringomyelia.

We recorded electrically stimulated somatosensory evoked potentials (electric SEPs) and pain-related SEPs following CO2 laser stimulation (CO2 laser SEPs) from a 17-year-old patient affected by myotonic dystrophy whose MRI disclosed a large syrinx extending from spinal level C2 to S3. Careful clinical and electromyographic examinations revealed no motor or sensory disturbances, apart from myotonia. The only abnormality noted in median and ulnar nerve short-latency electric SEPs (recorded with a non-cephalic reference electrode) was the absence of cervical component N13, the other SEP responses…

Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients.

OBJECTIVE: Information about pregnancy and delivery in hereditary neuromuscular disorders (NMD) is limited and largely restricted to small case series and single case reports. Further data of obstetric histories in clinically and genetically defined subgroups are required. STUDY DESIGN: We reviewed the obstetric histories of 178 patients with myotonic dystrophy type 1 (DM1) and 2 (DM2), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), and congenital myopathy (CM) by means of questionnaires a…

Неинвазивная вентиляция для стенки грудной клетки и нервно-мышечных расстройств.

Нейромускульные расстройства и нарушения стенки грудной клетки в индивидуальном порядке редки, но вместе они образуют важную группу заболеваний, которые могут привести к хронической недостаточности вентиляции. Это лучше всего распознается в сколиозе, кифозе, после грудной пластики, в мышечных дистрофиях, таких, как мышечная дистрофия Дюченна (DMD) и миотонная дистрофия, после полиомиелита и с моторной нейронной болезнью (амитрофический боковой склероз). В случае нарушения функции луковицы может потребоваться вентиляция трахеостомии, однако в других случаях предпочтительным является неинвазивна

Совпадение в аннотации оригинала
Neuromuscular and chest wall disorders are individually uncommon but together form an important group of conditions that can lead to chronic ventilatory failure. This is best recognised in scoliosis, kyphosis, following a thoracoplasty, in muscular dystrophies, such as Duchenne muscular dystrophy (DMD), and myotonic dystrophy, after poliomyelitis and with mo…