Query: myotubular myopathy

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Total 4359 results found since Jan 2013.

Cerebrospinal fluid ATP as a potential biomarker in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes (MELAS)
Publication date: Available online 19 November 2019Source: MitochondrionAuthor(s): Takamasa Nukui, Atsushi Matsui, Hideki Niimi, Mamoru Yamamoto, Noriyuki Mastuda, Jin-Lan Piao, Kyo Noguchi, Isao Kitajima, Yuji NakastujiAbstractMitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is caused by defective oxidative phosphorylation in the cerebral parenchyma, cerebral blood vessels, and leptomeningeal tissue. Although increased serum and cerebrospinal fluid (CSF) lactate level has been used as a diagnostic biomarker in patients with MELAS, no biomarkers reflecting disease activity exist. Since we hav...
Source: Mitochondrion - November 20, 2019 Category: Biochemistry Source Type: research

Significance of Asymptomatic Hyper Creatine-Kinase Emia
Conclusions: Recurrent AHCE should be taken seriously and managed with conventional work-up. If noninformative, genetic work-up should follow irrespective of the family history.
Source: Journal of Clinical Neuromuscular Disease - November 20, 2019 Category: Neurology Tags: Review Article Source Type: research

Inflammatory myopathy following acute meningoccemia in a properdin-deficient patient: A case report.
CONCLUSION: Post-infectious inflammatory myopathy should be suspected in case of severe and persistent myalgia associated with rhabdomyolysis following an IMD, after exclusion of pyomyositis especially. A short course of corticosteroids seems to be effective. PMID: 31735371 [PubMed - as supplied by publisher]
Source: Revue de Medecine Interne - November 19, 2019 Category: Internal Medicine Tags: Rev Med Interne Source Type: research

Drug-Induced Liver Injury from Statins
The hydroxymethyglutaryl-coenzyme A reductase inhibitors (statins) are a commonly prescribed class of medication for the treatment of hyperlipidemia and coronary artery disease. This class of medication has several proven benefits, including reduction of mortality related to coronary artery disease. A major consideration when prescribing these drugs are the potential for adverse effects, mainly myalgias, myopathy, and hepatotoxicity. In this article, we summarize current data on statin-associated hepatotoxicity and highlight that the risk of clinically significant idiosyncratic drug-induced liver injury is actually quite s...
Source: Clinics in Liver Disease - November 19, 2019 Category: Gastroenterology Authors: Lindsay Meurer, Stanley Martin Cohen Source Type: research

X-Linked Myopathy with Excessive Autophagy; A Case Report
We report this rare condition in a 5-year-old boy with proximal muscle weakness and morphological evidence of autophagic vacuoles.
Source: Neurology India - November 19, 2019 Category: Neurology Authors: Shilpa Rao SR Chandra Gayathri Narayanappa Source Type: research

Sequential activation of STIM1 links Ca2+ with luminal domain unfolding
The stromal interaction molecule 1 (STIM1) has two important functions, Ca2+ sensing within the endoplasmic reticulum and activation of the store-operated Ca2+ channel Orai1, enabling plasma-membrane Ca2+ influx. We combined molecular dynamics (MD) simulations with live-cell recordings and determined the sequential Ca2+-dependent conformations of the luminal STIM1 domain upon activation. Furthermore, we identified the residues within the canonical and noncanonical EF-hand domains that can bind to multiple Ca2+ ions. In MD simulations, a single Ca2+ ion was sufficient to stabilize the luminal STIM1 complex. Ca2+ store deple...
Source: Signal Transduction Knowledge Environment - November 19, 2019 Category: Science Authors: Schober, R., Bonhenry, D., Lunz, V., Zhu, J., Krizova, A., Frischauf, I., Fahrner, M., Zhang, M., Waldherr, L., Schmidt, T., Derler, I., Stathopulos, P. B., Romanin, C., Ettrich, R. H., Schindl, R. Tags: STKE Research Articles Source Type: news

Mutations in the J domain of DNAJB6 cause dominant distal myopathy
Mutations in DNAJB6 were identified in 2012 to cause autosomal dominant limb-girdle muscular dystrophy type 1D (LGMD1D, OMIM 603511; current proposed nomenclature LGMD D1 DNAJB6-related) [1,2]. Later, several other DNAJB6 mutations have been identified in Asian, European and North American populations [3 –11]. Interestingly, all reported mutations have affected the glycine/phenylalanine-rich (G/F) domain of DNAJB6. LGMD1D was originally described as late-onset, slowly progressive disease, most patients remained ambulant even at high age.
Source: Neuromuscular Disorders - November 19, 2019 Category: Neurology Authors: Johanna Palmio, Per Harald Jonson, Michio Inoue, Jaakko Sarparanta, Rocio Bengoechea, Marco Savarese, Anna Vihola, Manu Jokela, Masanori Nakagawa, Satoru Noguchi, Montse Oliv é, Marion Masingue, Emilia Kerty, Peter Hackman, Conrad C. Weihl, Ichizo Nishin Source Type: research

The Inherited Neuromuscular Disorder GNE Myopathy: Research to Patient Care
Kapila Awasthi, Ranjana Arya, Alok Bhattacharya, Sudha BhattacharyaNeurology India 2019 67(5):1213-1219 Inherited neuromuscular diseases are a heterogeneous group of rare diseases for which the low general awareness leads to frequent misdiagnosis. Advances in DNA sequencing technologies are changing this situation, and it is apparent that these diseases are not as rare as previously thought. Knowledge of the pathogenic variants in patients is helping in research efforts to develop new therapies. Here we present a review of current knowledge in GNE myopathy, a rare neuromuscular disorder caused by mutations in the GNE gene...
Source: Neurology India - November 19, 2019 Category: Neurology Authors: Kapila Awasthi Ranjana Arya Alok Bhattacharya Sudha Bhattacharya Source Type: research

Corticosteroid-sparing benefit of intravenous immunoglobulin in systemic sclerosis-associated myopathy: A comparative study in 52 patients
ConclusionsThis study suggests the benefit of IVIg as adjunctive therapy, with an acceptable tolerance profile, and supports its use as a CS-sparing agent, in SScAM.
Source: Autoimmunity Reviews - November 15, 2019 Category: Allergy & Immunology Source Type: research

HFpEF Is the Substrate for Stroke in Obesity and Diabetes Independent of Atrial Fibrillation
Publication date: Available online 6 November 2019Source: JACC: Heart FailureAuthor(s): Milton PackerAbstractBoth obesity and type 2 diabetes are important risk factors for the development of heart failure with a preserved ejection fraction (HFpEF), and both disorders increase the risk of systemic thromboembolic events. Traditionally, the risk of stroke has been explained by the strong association of these disorders with atrial fibrillation (AF). However, adiposity and diabetes are risk factors for systemic thromboembolism, even in the absence of AF, because both can lead to the development of an inflammatory and fibrotic ...
Source: JACC: Heart Failure - November 8, 2019 Category: Cardiology Source Type: research

Toward a Diagnostic Score in Cushing's Syndrome
This article provides an overview about the current standard in the diagnosis of CS starting with clinical scores and screenings, the clinical signs, relevant differential diagnoses, the first-line biochemical screening, and ending with a few exceptional cases.
Source: Frontiers in Endocrinology - November 8, 2019 Category: Endocrinology Source Type: research

GNE myopathy- A cross-sectional study on spatio-temporal gait characteristics
GNE myopathy is a rare disease, which is also known by other names like Nonaka myopathy, distal myopathy with rimmed vacuoles-DMRV, hereditary inclusion body myopathy-HIBM, Inclusion body myopathy 2-IBM2 and quadriceps sparing myopathy. It has a prevalence of 1-21/1,000,000 population. [1 –5] It is an autosomal recessive disease caused by bi-allelic inheritance of variable mutations in the GNE gene on chromosome 9, encoding a bifunctional enzyme- uridine diphosphate-N-acetylglucosamine 2-epimerase /N-acetylmannosamine kinase required in sialic acid- 5-N-acetylneuraminic acid (Neu5A c) synthesis, which in turn plays a rol...
Source: Neuromuscular Disorders - November 8, 2019 Category: Neurology Authors: Gaurav Gomez, Meeka Khanna, Anupam Gupta, Atchayaram Nalini, K. Thennarasu, Saraswati Nashi, Kiran Polavarapu, Seena Vengalil Source Type: research

Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1
ConclusionsIn this study, we describe the structural brain signatures that delineate the involvement of the CNS in DM1. We show that specific sensory and multi-sensory — as well as frontal cortical areas — display potential vulnerability associated with the hypothesized neurodegenerative nature of DM1 brain abnormalities.
Source: NeuroImage: Clinical - November 7, 2019 Category: Radiology Source Type: research

The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics
ConclusionThe LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.
Source: American Heart Journal - November 7, 2019 Category: Cardiology Source Type: research

Understanding the life experience of Barth syndrome from the perspective of adults: a qualitative one-on-one interview study
Barth syndrome (BTHS, OMIM 302060) is a rare, life-threatening, x-linked genetic disorder that occurs almost exclusively in males and is characterized by cardiomyopathy, neutropenia, skeletal muscle myopathy p...
Source: Orphanet Journal of Rare Diseases - November 7, 2019 Category: Internal Medicine Authors: Iyar Mazar, Jonathan Stokes, Sarah Ollis, Emily Love, Ashlee Espensen, Peter G. Barth, John H. Powers III and Alan L. Shields Tags: Research Source Type: research

Congenital fiber type disproportion caused by TPM3 mutation: a report of two atypical cases.
Congenital fiber type disproportion (CFTD, MIM #255310) is a histologically and genetically heterogeneous type of congenital myopathy defined by slow type1 fiber hypotrophy in the absence of any other major structural abnormalities in the skeletal muscle tissue [1]. Clinically patients manifest with a variable range of hypotonia and generalized muscle weakness at birth, developing with a high-arched palate, proximal weakness and thoracic and spinal deformities and contractures. Respiratory involvement is described in 30% of the patients.
Source: Neuromuscular Disorders - November 7, 2019 Category: Neurology Authors: Cristiane de Ara újo Martins Moreno, Eduardo de Paula Estephan, Alan Fappi, Soledad Monges, Fabiana Lubieniecki, Osório Lopes Abath Neto, Umbertina Conti Reed, Sandra Donkervoort, Matthew B. Harms, Carsten Bonnemann, Edmar Zanoteli Tags: Case report Source Type: research

Statins for children with familial hypercholesterolemia.
CONCLUSIONS: Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins. PMID: 31696945 [PubMed - in process]
Source: Cochrane Database of Systematic Reviews - November 7, 2019 Category: General Medicine Authors: Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Tonstad S, Wiegman A, Drogari E, Ramaswami U Tags: Cochrane Database Syst Rev Source Type: research

Differentiating Congenital Myopathy from Congenital Muscular Dystrophy
The congenital muscular dystrophies and congenital myopathies are a heterogenous group of diseases with a wide variety of presentations and outcomes. With the growing understanding of genetic involvement, and developing therapies, having a genetically confirmed diagnosis with phenotype correlation is essential. To achieve this, a structured approach is warranted to each child to ensure that mimickers are excluded. By structuring the evaluation appropriately, the clinician can help expedite the evaluation of these infants in a cost-effective manner. Understanding the pitfalls of each step of testing will allow the clinician...
Source: Clinics in Perinatology - November 7, 2019 Category: Perinatology & Neonatology Authors: Matthew Harmelink Source Type: research

A childhood-onset nemaline myopathy caused by novel heterozygote variants in the nebulin gene with literature review
We report two novel compound heterozygous variants in nebulin gene in a family residing in China. One is an intron event caused by an underlying variant at the +  3 position of the donor site. Another is a novel nonsense variant, which may lead to the end of protein translation and have a significant impact on protein function. The pathogenicity of this novel compound heterozygous variant remains to be verified. Variants reported here could help to diagnos e NM for clinicians.
Source: Acta Neurologica Belgica - November 6, 2019 Category: Neurology Source Type: research

Heteroplasmy and phenotype spectrum of the mitochondrial tRNALeu (UUR) gene m.3243A > G mutation in seven Han Chinese families
The m.3243A  > G mutation in the mitochondrial tRNALeu (UUR) gene is associated with a variety of phenotypic heterogeneity. The clinical spectrum and phenotypic-genotypic correlations in the Chinese patients are poorly understood. In the present study, we reported the clinical and genetic characterization, as w ell as haplogroups of seven Han Chinese families carrying the m.3243A > G mutation. Of the 39 matrilineal individuals, five suffered from mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), two had life-threatening mitochondrial myopathy (LTMM), and one patient had neuropathy,...
Source: Journal of the Neurological Sciences - November 6, 2019 Category: Neurology Authors: Gailing Liu, Xiya Shen, Yongan Sun, Qing Lv, Yuanyuan Li, Ailian Du Source Type: research

A missed protective drug –drug interaction of DPP-4 inhibitors and statins on myopathy risk
Source: Acta Diabetologica - November 6, 2019 Category: Endocrinology Source Type: research

GSE104996 Altered gene expression in liver and muscle of ADCK2(+/-) mouse
Contributors : Daniel J Fern ández-Ayala ; Rafael deCabo ; Plácido NavasSeries Type : Expression profiling by arrayOrganism : Mus musculusAnalysis of gene expression in both muscle and liver due to the lost of one copy of the gene ADCK2. Heterocygous mouse ADCK2(+/-) present an altered gene expression that explain the adult phenotype, including myopathy in muscle and steatosis and inflamation in liver.
Source: GEO: Gene Expression Omnibus - November 4, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research

Efficacy and Safety of High-intensity Statins in Patients with Acute Myocardial Infarction: An Asian Perspective
ConclusionsAMI patients in Taiwan with HIS had similar clinical outcomes to those with non-HIS. Using HIS for effective reduction of low-density lipoprotein cholesterol is safe in Taiwan.
Source: Canadian Journal of Cardiology - November 2, 2019 Category: Cardiology Source Type: research

A Case of β-Carotenemia Misdiagnosed as Jaundice by the Bilirubin Oxidase Method.
Authors: Kiuchi S, Ihara H, Koyasu M, Tani A, Hashizume N Abstract Serum bilirubin measurement is necessary to accurately distinguish jaundice from carotenemia. A 59.8-y old Japanese male showed symptoms of yellow skin pigmentation as a result of β-carotenemia. Diagnostic laboratory results indicated elevated levels of serum muscle enzymes (aspartate aminotransferase, lactate dehydrogenase, and creatine kinase), but normal levels in liver function tests (alanine aminotransferase and direct bilirubin). The laboratory results indicated hypothyroid myopathy. Moreover, although the patient did not show significant abn...
Source: Journal of Nutritional Science and Vitaminology - November 1, 2019 Category: Nutrition Tags: J Nutr Sci Vitaminol (Tokyo) Source Type: research

Inspiratory muscle training for advanced heart failure with lamin-related muscular dystrophy
Publication date: Available online 29 October 2019Source: Journal of Cardiology CasesAuthor(s): Masanobu Taya, Eisuke Amiya, Masaru Hatano, Hisataka Maki, Yumiko Hosoya, Junichi Ishida, Chie Bujo, Masaki Tsuji, Yuto Konishi, Kazuhiko Yokota, Nobuhiko Haga, Issei KomuroAbstractRespiratory muscle weakness is often complicated in patients with heart failure. Its presence further worsens the clinical course of heart failure. However, the effect and appropriate method of inspiratory muscle training has not previously been elucidated.A 55-year-old man with dilated cardiomyopathy was admitted for intractable heart failure. His he...
Source: Journal of Cardiology Cases - October 30, 2019 Category: Cardiology Source Type: research

Treatment with Statins in Elderly Patients.
Abstract Elderly patients are a special category of patients, due to the physiological changes induced by age, the great number of comorbidities and drug treatment and last, but not least, to the cognitive dysfunction frequently encountered in this population. Cardiovascular disease is the most important cause of morbidity and mortality in elderly individuals worldwide. The rate of cardiovascular events increases after 65 years in men and after 75 years in women. Myocardial infarction and stroke are the leading disorders caused by atherosclerosis, that lead to death or functional incapacity. Elderly people have a ...
Source: Medicina (Kaunas) - October 30, 2019 Category: Universities & Medical Training Authors: Horodinschi RN, Stanescu AMA, Bratu OG, Pantea Stoian A, Radavoi DG, Diaconu CC Tags: Medicina (Kaunas) Source Type: research

Structural and functional characterization of D109H and R69C mutant versions of human αB-crystallin: the biochemical pathomechanism underlying cataract and myopathy development.
In conclusion, the R69C and D109H mutations displayed a significant damaging effect on the structure and chaperone function of human αB-Cry which could be considered as their biochemical pathomechanisms in development of congenital cataract and myopathy disorders. PMID: 31678106 [PubMed - as supplied by publisher]
Source: International Journal of Biological Macromolecules - October 30, 2019 Category: Biochemistry Authors: Ghahramani M, Yousefi R, Krivandin A, Muranov K, Kurganov B, Akbar Moosavi-Movahedi A Tags: Int J Biol Macromol Source Type: research

Electromyographic activity and kinematics of sit-to-stand in individuals with muscle disease
ConclusionWe observed that individuals with muscle disease are able to stand up in a similar sit-to-stand pattern to healthy individuals with longer duration and higher muscle activation levels. Prolonged high muscle activation during functional activities may cause fatigue and muscle destruction in patients. For this reason, planning of exercise programs for appropriate muscles and phases will enable the patients to perform the activity of sit-to-stand more easily. Thus, patients will become more functional and independent in their daily lives with less effort.
Source: Neurological Sciences - October 28, 2019 Category: Neurology Source Type: research

Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells.
Abstract Lysosome-associated membrane protein-2 (LAMP2), is a highly glycosylated lysosomal membrane protein involved in chaperone mediated autophagy. Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). Additionally, retinopathy has also been observed in young DD patients, leading to vision loss. Emerging evidence show LAMP2-deficiency to be involved in oxidative stress (ROS) but the mechanism remains obscure. In the present study, we found that tert-butyl hydroperoxide or antimycin A induced more cell death in LAMP2 knockdown (LAMP2-KD) than in control ...
Source: Biochemical and Biophysical Research communications - October 28, 2019 Category: Biochemistry Authors: Lee JJ, Ishihara K, Notomi S, Efstathiou NE, Ueta T, Maidana D, Chen X, Iesato Y, Caligiana A, Vavvas DG Tags: Biochem Biophys Res Commun Source Type: research

Growth and Differentiation Factor 15 as a biomarker for mitochondrial myopathy
Publication date: Available online 26 October 2019Source: MitochondrionAuthor(s): Nanna Scharff Poulsen, Karen Lindhardt Madsen, Tessa Munkeboe Hornsyld, Anne-Sofie Vibæk Eisum, Freja Fornander, Astrid Emilie Buch, Mads Godtfeldt Stemmerik, Cristina Ruiz-Ruiz, Thomas Oliver Krag, John VissingAbstractObjectiveWe investigated if Growth and Differentiation Factor 15 (GDF-15) can be used as a biomarker to distinguish patients with mitochondrial myopathy from patients with other myopathies.MethodsSerum GDF-15 was measured in 28 patients with mitochondrial disease, 24 with metabolic myopathies, 27 with muscular dystrophy and 21...
Source: Mitochondrion - October 26, 2019 Category: Biochemistry Source Type: research

Neutral lipid storage disease with myopathy in China: a large multicentric cohort study
Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents ske...
Source: Orphanet Journal of Rare Diseases - October 26, 2019 Category: Internal Medicine Authors: Wei Zhang, Bing Wen, Jun Lu, Yawen Zhao, Daojun Hong, Zhe Zhao, Cheng Zhang, Yuebei Luo, Xueliang Qi, Yingshuang Zhang, Xueqin Song, Yuying Zhao, Chongbo Zhao, Jing Hu, Huan Yang, Zhaoxia Wang & hellip; Tags: Research Source Type: research

Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a single-center experience with 63 patients.
CONCLUSIONS: IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection. PMID: 31653191 [PubMed - as supplied by publisher]
Source: Lupus - October 25, 2019 Category: Rheumatology Authors: Nieto-Aristizábal I, Martínez T, Urbano MA, Posso-Osorio I, Plata IF, Garcia-Robledo JE, Aragón CC, Santos VA, Tobón GJ Tags: Lupus Source Type: research

A novel homoplasmic mitochondrial DNA mutation (m.13376T > C, p.I347T) of MELAS presenting characteristic medial temporal lobe atrophy
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial cytopathy that usually affects people under 40  years of age with variable symptoms [1]. The prevalence of MELAS syndrome in Japan was reported to be 0.2: 100,000 [2]. MELAS can be diagnosed by serum analyses under an aerobic exercise test, brain magnetic resonance imaging (MRI), muscle biopsy and mitochondrial DNA (mtDNA) analysis [3]. Approx imately 80% of MELAS cases are caused by a mutation m.3243A > G of the mitochondrial transfer RNA gene [4].
Source: Journal of the Neurological Sciences - October 25, 2019 Category: Neurology Authors: Ryo Sasaki, Yasuyuki Ohta, Noriko Hatanaka, Koh Tadokoro, Emi Nomura, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yoshio Omote, Eisaku Morimoto, Sanae Teshigawara, Jun Wada, Yu-ichi Goto, Koji Abe Tags: Letter to the Editor Source Type: research

Mitochondrial myopathy plus due to the variant m.586G > A in MT-TF
Publication date: December 2019Source: Molecular Genetics and Metabolism Reports, Volume 21Author(s): Giulia Barcia, Zahra Assouline, Alessandra Pennisi, Julie Steffann, Nathalie Boddaert, Cyril Gitiaux, Agnès Rötig, Jean-Paul Bonnefont, Arnold Munnich
Source: Molecular Genetics and Metabolism Reports - October 23, 2019 Category: Genetics & Stem Cells Source Type: research

Human muscle pathology is associated with altered phosphoprotein profile of mitochondrial proteins in the skeletal muscle.
Abstract Analysis of human muscle diseases highlights the role of mitochondrial dysfunction in the skeletal muscle. Our previous work revealed that diverse upstream events correlated with altered mitochondrial proteome in human muscle biopsies. However, several proteins showed relatively unchanged expression suggesting that post-translational modifications, mainly protein phosphorylation could influence their activity and regulate mitochondrial processes. We conducted mitochondrial phosphoprotein profiling, by proteomics approach, of healthy human skeletal muscle (n = 10) and three muscle diseases (n = 10 ...
Source: Journal of Proteomics - October 23, 2019 Category: Biochemistry Authors: Sunitha B, Kumar M, Gowthami N, Unni S, Gayathri N, Prasad TSK, Nalini A, Polavarapu K, Vengalil S, Preethish-Kumar V, Padmanabhan B, Bharath MMS Tags: J Proteomics Source Type: research

Case 22-2019: A 65-Year-Old Woman with Myopathy
New England Journal of Medicine,Volume 381, Issue 17, Page 1693-1694, October 2019.
Source: New England Journal of Medicine - October 23, 2019 Category: Internal Medicine Source Type: research

Impairment of mitochondrial bioenergetics and permeability transition induction caused by major long-chain fatty acids accumulating in VLCAD deficiency in skeletal muscle as potential pathomechanisms of myopathy.
Abstract cis-5-Tetradecenoic (cis-5) and myristic (Myr) acids predominantly accumulate in patients affected by very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. They commonly manifest myopathy with muscular pain and rhabdomyolysis, whose underlying mechanisms are poorly known. Thus, in the present study we investigated the effects of cis-5 and Myr on mitochondrial bioenergetics and Ca2+ homeostasis in rat skeletal muscle. cis-5 and Myr decreased ADP-stimulated (state 3) and CCCP-stimulated (uncoupled) respiration, especially when mitochondria were supported by NADH-linked as compared to FADH2-linked subst...
Source: Toxicology in Vitro - October 16, 2019 Category: Toxicology Authors: Cecatto C, Amaral AU, Roginski AC, Castilho RF, Wajner M Tags: Toxicol In Vitro Source Type: research

Paraspinal amyotrophy in DNM-2-related centronuclear myopathy
Centronuclear myopathy (CNM) is a rare congenital myopathy characterized by the morphological feature of centrally located nuclei in a large number of muscle fibers. CNM is related to several causative genes: dynamin 2 (DNM2), myotubularin (MTM1), amphiphysin 2 (BIN1), and ryanodine receptor 1 (RYR1) [1]. DNM2-related CNM (DNM2-CNM) is an autosomal-dominant inherited disease that accounts for about 50% of CNM cases [1]. Although DNM2-CNM has shown a variety of clinical manifestations, from severe neonatal onset to mild adult onset, most patients present with slowly progressive muscle weakness in the distal or sometimes pro...
Source: Journal of the Neurological Sciences - October 16, 2019 Category: Neurology Authors: Kensuke Kakiuchi, Kiichi Unoda, Hideto Nakajima, Ichizo Nishino, Shigeki Arawaka Tags: Letters to the Editor Source Type: research

Quantitative nuclear magnetic resonance imaging detects subclinical changes over 1 year in skeletal muscle of GNE myopathy
ConclusionsEven in a limited number of patients, qNMRI could detect a significant change over a 1-year period in GNE myopathy, which suggests that qNMRI could constitute a surrogate endpoint in this slowly progressive disease. Quantitative NMRI outcome measures can monitor intramuscular fat accumulation with high responsiveness. Longer follow-up should improve our understanding of GNE myopathy evolution and also lead to the identification of non-invasive outcome measures with the highest discriminant power for upcoming clinical trials.
Source: Journal of Neurology - October 15, 2019 Category: Neurology Source Type: research

Distal myopathy induced arrhythmogenic right ventricular cardiomyopathy in a pedigree carrying novel DSG2 null variant
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease predominantly caused by variants in desmosome genes. Variants in human Desmoglein-2 (DSG2) gene can cause ARVC with incomplete penetrance. However, it remains unknown whether ARVC would penetrate by distal myopathy.
Source: International Journal of Cardiology - October 7, 2019 Category: Cardiology Authors: Peng Chen, Zongzhe Li, Bo Yu, Fei Ma, Xianqing Li, Dao Wen Wang Source Type: research

Hypoxia inducible factor-prolyl hydroxylase inhibitor ameliorates the myopathy in a mice model of chronic kidney disease.
Abstract Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Pro-angiogenesis therapy is therefore considered a potentially effective strategy for limiting CKD-associated myopathy. The hypoxia inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia, however, little evidence was available from CKD models. Here, we assessed whether the pharmac...
Source: American Journal of Physiology. Renal Physiology - October 7, 2019 Category: Physiology Authors: Qian FY, Li ZL, Guo YD, Gao HC, Gu LH, Le K, Xie CM, Wang B, Zhang ZJ Tags: Am J Physiol Renal Physiol Source Type: research

EP.101Clinical, histopathological and molecular characterization of a cohort of Spanish patients with congenital myopathy
Congenital myopathies are a heterogeneous group of inherited disorders that mainly affect muscle tissue. Hypotonia and muscle weakness, with neonatal or childhood onset, are the most typical presentations. The predominance of particular histopathological findings classifies them into subtypes. Clinical, histopathological and molecular characterization of a cohort of patients with congenital myopathy. A retrospective descriptive study was conducted in an historic cohort of 105 patients registered with clinical and histopathological diagnosis of congenital myopathy.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: D. Natera de Benito, C. Jou, C. Jimenez-Mallebrera, C. Ortez, A. Codina, L. Carrera Garcia, J. Exposito Escudero, J. Colomer Oferil, F. Palau, A. Nascimento Source Type: research

P.106Mutation-specific therapy for X-linked myotubular myopathy
X-linked myotubular myopathy (XLMTM) is a severe congenital myopathy due to mutations in MTM1 encoding a 3-phosphoinositides phosphatase myotubularin. XLMTM patients display severe generalized hypotonia at birth accompanied by respiratory insufficiency and pathologically show small-size fibers with peripheral halo, centrally located nuclei, disorganized perinuclear organelles in the muscle. Among 78 patients with pathologically diagnosed as XLMTM in our cohort, causative mutations were not identified in 20 cases by targeted re-sequencing panel for congenital myopathy, MTM1 Sanger sequencing nor Whole-exome sequencing.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: S. Hayashi, S. Noguchi, T. Kumutpongpanich, A. Iida, M. Okubo, M. Matsuo, I. Nishino Source Type: research

P.105INCEPTUS pre-phase 1, prospective, non-interventional, natural history run-in study to evaluate subjects aged 4 years and younger with X-linked myotubular myopathy (XLMTM)
XLMTM is a rare disease caused by mutations in the MTM1 gene, leading to profound muscle weakness, respiratory failure and early death. INCEPTUS (NCT02704273) is a prospective, non-interventional study in patients (pts) ≤4 years old to characterize the course and natural history of XLMTM using neuromuscular and respiratory assessments and to identify adverse events (AEs). INCEPTUS will generate within-pt control data to support a Phase 1/2 gene therapy clinical trial (ASPIRO). As of 22MAR19, 32 male pts (0.3-4.6 years of age) have been enrolled and assessed every 3 months for up to 24 months.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: L. Servais, P. Shieh, J. Dowling, N. Kuntz, W. M üller-Felber, B. Smith, C. Bönnemann, F. Muntoni, D. Bilder, T. Duong, R. Graham, M. Jain, M. Lawlor, V. MacBean, M. Noursalehi, T. Pitts, G. Rafferty, S. Rico, S. Prasad Source Type: research

P.104Skeletal muscle reduction of Dnm2 with antisense oligonucleotides in myotubular myopathy
Centronuclear myopathies (CNM) are a group of severe muscle diseases for which no effective therapy is currently available. The most severe and neonatal X-linked form is known as myotubular myopathy and caused by loss-of-function mutations in Myotubularin (MTM1), while the main autosomal dominant form is due to mutations in Dynamin 2 (DNM2). We previously showed that genetic reduction of DNM2 expression in Mtm1 knockout (Mtm1KO) mice prevents development of muscle pathology. We are now investigating skeletal muscle targeting of Dnm2 reduction in mice.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: S. Buono, A. Rob é, R. Gomez Oca, C. Koch, S. Guo, M. Depla, B. Monia, J. Laporte, L. Thielemans, B. Cowling Source Type: research

P.295Linked-read whole genome sequencing in patients with congenital myopathy
In this study, we wanted to test whether a new NGS application — the Linked-Read (LR) library preparation — can improve the identification of disease-causing variants in patients with congenital myopathy. For LR library preparation, gDNA molecules are encapsulated inside emulsion droplets.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: J. Lehtonen, V. Lehtokari, H. Almusa, A. Sulonen, J. Saarela, C. Wallgren-Pettersson, K. Pelin Source Type: research

P.257Analysis of 34 Korean patients of GNE mutations associated distal myopathy with rimmed vacuoles
GNE myopathy is an autosomal recessive disorder caused by mutations in the GNE on chromosome 9p1-q1, which encodes the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. GNE myopathy is characterized by adult-onset muscle weakness and atrophy starting from the tibialis anterior, except for quadriceps. The majority of GNE variants (about 80%) are missense mutations scattered through the epimerase and kinase domains. The present study reviewed thirty-four patients with genetically confirmed GNE myopathy conducted from 2003 to 2018.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: Y. La, J. Lee, H. Park, Y. Choi Source Type: research

Quantum Blue Reduces the Severity of Woody Breast Myopathy via Modulation of Oxygen Homeostasis-Related Genes in Broiler Chickens
In this study, using diffuse reflectance spectroscopy (DRS) coupled with iSTAT portable clinical analyzer, we provide evidence that the circulatory- and breast muscle-oxygen homeostasis is dysregulated [low oxygen and hemoglobin (HB) levels] in chickens with WB myopathy compared to healthy counterparts. Molecular analysis showed that blood HB subunit Mu (HBM), Zeta (HBZ), and hephaestin (HEPH) expression were significantly down regulated; however, the expression of the subunit rho of HB beta (HBBR) was upregulated in chicken with WB compared to healthy counterparts. The breast muscle HBBR, HBE, HBZ, and hypoxia-inducible f...
Source: Frontiers in Physiology - October 1, 2019 Category: Physiology Source Type: research

EP.132Central core myopathy in Chinese patients with Nav1.4 p.R675Q mutation
Nav1.4 (SCN4A) p.R675Q is the most common mutation in Chinese patients with skeletal muscle sodium channelopathies. Two patients with R675Q mutation from different neuromuscular diagnosis centers complained of fixed myopathy and recurrent periodic paralysis. Muscle biopsy on biceps were performed for both patients. Clinical features as well as muscle MRI in bilateral lower limbs were retrospectively reviewed. To further explore the underlying mechanism of the central core-like pathology, we performed the immunofluorescence staining (IF) and western blot of Ryanodine receptor-1 (RYR1) and calcium channel voltage-dependent L...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: J. Sun, S. Luo, M. Gao, K. Qiao, H. Lv, C. Zhao Source Type: research

EP.123Selenoprotein-related congenital myopathy in two siblings
Selenoprotein-related myopathy (SEPN1-RM) is a rare disease with a variable clinical presentation. Typically, patients have early onset respiratory insufficiency and relatively preserved limb muscle strength. Although the precise function of SEPN1 protein is uncertain, recent studies suggest a role in cell protection against oxidative stress. Prominent involvement of diaphragm muscle and skeletal muscle which are more vulnerable to oxidative stress probably may cause early respiratory involvement.
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: O. Herguner, S. Bilge, N. Ozcan, G. Gul Mert, D. Ozcanyuz, F. Incecik, S. Altunbasak Source Type: research