Query: myotubular myopathy

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Total 4837 results found since Jan 2013.

Preliminary Observations and Experiences of Physiotherapy Practice in Acute Care Setup of COVID 19: A Retrospective Observational Study.
Conclusion: Most common form of physiotherapy interventions in patients with Covid 19 were therapeutic positioning, early mobilization and breathing exercises. Physiotherapy intervention appears promising in facilitating early patient ambulation and discharge. This study shows that it is safe and feasible to provide early physiotherapy treatment techniques in patients with COVID-19 using appropriate measures of infection prevention and cross contamination. PMID: 32978920 [PubMed - in process]
Source: Journal of the Association of Physicians of India - September 29, 2020 Category: General Medicine Tags: J Assoc Physicians India Source Type: research

Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Myopathy: An Unusual Presentation
No abstract available
Source: JCR: Journal of Clinical Rheumatology - September 29, 2020 Category: Rheumatology Tags: Images Source Type: research

Muscle function & homeostasis / molecular therapeutic approaches
The Y-box binding protein 3 (YBX3) has been described as a transcriptional regulator and translational repressor of various proteins in skeletal and heart muscle. Its functions include, among others, the gradual repression of myogenin during myogenesis. By exome sequencing in a Finnish patient with an unusual form of nemaline myopathy, we have found two rare YBX3 variants, NP_003642.3:p.(Ser34Arg) and NP_003642.3:p.(Arg129Trp). Our previous results have shown that the variants affect the localisation of the protein and its post-translational modifications in transiently transfected cell cultures.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: L. Sagath, J. Blondelle, J. Laitila, V. Lehtokari, K. Kiiski, M. Gr önholm, C. Wallgren-Pettersson, S. Lange, K. Pelin Source Type: research

Muscle function & homeostasis / molecular therapeutic approaches
Nebulin (600-900 kDa) is a giant filamentous protein located in the thin filament of the skeletal muscle sarcomere. It has a highly modular structure, consisting of more than 200 actin-binding simple repeats along the length of the protein. The simple repeats in the central part of the protein are further organised into super repeats (numbered S1-S22). Mutations in the nebulin gene (NEB, 183 exons) are the most common cause of recessively inherited nemaline myopathy. Due to extensive alternative splicing, hundreds of different nebulin isoforms are expressed in skeletal muscle.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Laitila, M. Hanif, J. Sarparanta, J. Lehtonen, A. Khattab, M. Gr önholm, C. Wallgren-Pettersson, K. Pelin Source Type: research

Dmd & bmd – clinical
Duchenne/Becker muscular dystrophy (DMD/BMD) is a progressive skeletal myopathy as well as a cardiomyopathy. Historically, it is reported that patients with DMD/BMD experience significant morbidity/mortality as a result of rhythm abnormalities. However, natural history data is limited regarding the specific mode of death, e.g. heart failure vs. sudden cardiac death vs. non-cardiac death. We identified 82 patients at our institution to analyze retrospectively (67 DMD/15 BMD). Average age was 21 (range 10-38) years.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. Nealon, B. Beckman, N. Kertesz, L. Cripe Source Type: research

Myasthenia & related disorders
Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant rare disorder that is caused by mutations in the genes for voltage gated calcium channel CaV1.1 (CACNA1S) and NaV1.4 (SCN4A). Patients with hypoPP may suffer from periodic paralysis alone, periodic paralysis with weakness or permanent weakness. HypoPP has been known to be associated with vacuolar myopathy for decades but the cause of this has not been known. We have investigated a cohort of 14 hypoPP patients with the R528H mutation in the CACNA1S gene for vacuoles and their content.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: T. Krag, S. Holm-Yildiz, N. Witting, J. Vissing Source Type: research

Myasthenia & related disorders
Mutations in the sodium channel gene, SCN4A, encoding the Nav1.4 voltage-gated sodium channel, are well known causes of the skeletal muscle channelopathies: periodic paralyses (hyperkalemic, normokalemic, and hypokalemic periodic paralysis), paramyotonia congenita and other forms of myotonia. In addition, rare recessive SCN4A mutations have been associated with congenital myasthenic myopathy and congenital myopathy with hypotonia. To date over 40 dominant mutations in SCN4A have been reported to cause variable phenotypes depending on the type and location of the mutations.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Palmio, R. Mannikko, B. Udd Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) is a non-dystrophic congenital myopathy which currently has no therapy. The gene Nebulin (NEB) accounts for 50% of all cases of NM, with most patients being compound heterozygous for two different mutations in NEB. Patients with NM have significantly reduced levels of nebulin. Nebulin is a giant protein that is mainly expressed in the skeletal muscle, specifically in the sarcomeres. Most of the protein consists of repetitive repeats that help nebulin bind to the thin filament.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Viththiyapaskaran Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy is one of the most common congenital myopathies. The hallmarks of this disorder are early onset muscular weakness, hypotonia, pectus carinatum and rod-like inclusions in muscle cells. The severity spectrum of nemaline myopathy is broad, but early respiratory failure and death are the inevitable outcomes in most of the cases. Several gene mutations have been identified in nemaline myopathy, including a non-sense mutation in exon 11 of TNNT1 gene, encoding for the slow skeletal muscle isoform of troponin T (TnT), which results in selective atrophy of slow-twitch (type I) myofibers and in a unique form of Ne...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. D'Ambrosio, M. Sena-Esteves, H. GrayEdwards, M. Otero Source Type: research

Congenital myopathies 1 – nemaline
Inherited nemaline myopathies (iNM) are a genetically heterogeneous group of disorders characterized by accumulation of Z-disc derived nemaline rods in muscle fibres and presenting from infancy to adulthood. Nemaline rods are also a pathological feature of sporadic late onset nemaline myopathy (SLONM), an acquired myopathy sometimes associated with monoclonal gammopathies or HIV infection. We sought to identify pathological parameters distinguishing these two myopathies. This distinction has significant implications, as SLONM may respond to pharmacological therapy.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Nicolau, A. Dasgupta, D. Selcen, A. Engel, J. Doles, M. Milone Source Type: research

Congenital myopathies 1 – nemaline
We report the case of a 6 yo boy, born from consanguineous parents with typical phenotypic presentation for nemaline myopathy, proven on muscle biopsy.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: N. Chrestian, N. Laflamme, Y. Labrie, N. Rioux, M. Dugas, S. Rivest, B. Lace Source Type: research

Congenital myopathies 1 – nemaline
Congenital myopathies are a heterogeneous group of hereditary primary muscle disorders that are present from birth, although their onset may be delayed until later in infancy or early childhood. The most common of these rare disorders are nemaline myopathy, central core disease, centronuclear (myotubular) myopathies, and congenital fiber type disproportion. Among them, nemaline myopathy, a rare congenital myopathy, is characterized by generalized muscle weakness, respiratory insufficiency, and the presence of rod structures on muscle biopsy, which is caused by mutations in at least 13 known genes.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Lee, H. Park, Y. Choi Source Type: research

Congenital myopathies 1 – nemaline
Respiratory failure can be the initial presenting feature and is the most common cause of death in patients with nemaline myopathy. Surprisingly, data on respiratory muscle weakness, specifically diaphragm function, is scarce in these patients. Therefore, we performed a comprehensive characterization of respiratory muscle function, including diaphragm function, in patients with different nemaline myopathy mutations. We recruited children and adults with genetically confirmed nemaline myopathy with different mutations in the Netherlands.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. van Kleef, C. Ottenheijm, M. Gaytant, W. de Weerd, B. Vosse, B. van Engelen, N. Voermans, J. Doorduin Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) constitutes a clinically and genetically heterogeneous spectrum of muscle disorders. Until very recently, little or no scientific attention has been paid to the lived experience and functioning of people with neuromuscular disorders. The same is true for the impact of eating and nutrition on the daily life of these patients. Persons with NM often have weakness of the facial and bulbar muscles and secondary structural abnormalities of the oral region, complicating eating and swallowing, and likely affecting their nutritional state.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: V. Lehtokari, M. Tammepuu, M. Simil ä, S. Strang-Karlsson, S. Hiekkala, C. Wallgren-Pettersson Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) is a genetically and clinically heterogeneous disease that is diagnosed based on the presence of nemaline rods on skeletal muscle biopsy. Despite multiple genes and known mutations, the genetic heterogeneity of NM is not predictive of disease course, which suggests that unidentified secondary mechanisms exist that impact disease severity. We hypothesize that currently undetermined biological processes play a role in the muscle weakness of NM patients and that these can be revealed by examining disease signatures of NM mouse models.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: R. Slick, J. Tinklenberg, H. Meng, M. Beatka, M. Prom, E. Ott, F. Montanaro, L. Zhang, H. Granzier, E. Hardeman, A. Geurts, M. Lawlor Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) is a genetically and clinically heterogenous neuromuscular disorder that can cause death or lifelong disability. Essentially all genes associated with NM are related to the sarcomeric thin filament. Therefore, studies of weakness in NM have focused primarily on issues of skeletal muscle structure and contractility. However, the genetic variability seen does not explain the significant phenotypic heterogeneity observed in NM patients or mouse models, suggesting that additional factors determine disease phenotype.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Tinklenberg, R. Slick, J. Sutton, M. Prom, E. Ott, S. Danielson, M. Vanden Avond, M. Beatka, H. Meng, M. Grzybowski, J. Heisner, J. Ross, J. Ochala, K. Nowak, L. Zhang, A. Geurts, D. Stowe, F. Montanaro, M. Lawlor Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy type 6 (NEM6) is a rare congenital myopathy characterized by muscle weakness, exercise intolerance and muscle slowness, linked to autosomal dominant KBTBD13 gene mutations. Mutated KBTBD13 interacts improperly with thin filaments/actin provoking impaired muscle-relaxation kinetics. We performed a deep muscle phenotyping including immunohistochemistry and electron microscopy in 18 muscle biopsies of Dutch NEM6 patients in order to correlate muscle morphology with clinical phenotype and pathophysiological mechanisms.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: K. Bouman, B. K üsters, J. De Winter, C. Gllet, E. Van Kleef, L. Eshuis, G. Brochier, A. Madelaine, C. Labasse, C. Boulogne, B. Van Engelen, C. Ottenheijm, M. Olive, N. Romero, N. Voermans, E. Malfatti Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Immune-mediated necrotizing myopathy (IMNM) belongs to the group of idopathic inflammatory myopathies. Affected patients present with severe proximal lower-limb-predominant muscle weakness and strong elevation of the creatine kinase. The presence of anti-HMGCR- or anti-SRP- autoantibodies or the absence of known myositis specific antibodies is diagnostically essential and divides IMNM into three subgroups. Treatment with immune modulators can be effective, but escalation of therapy is often necessary.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: N. Fischer, C. Preusse, Y. Allenbach, O. Benveniste, A. Roos, H. Goebel, W. Stenzel Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
A subgroup of autophagic vacuolar myopathies (AVMs) is characterized by unusual autophagic vacuoles with sarcolemmal features (AVSFs) and includes Danon disease and X-linked myopathy with excessive autophagy (XMEA). We suggest referring to this subgroup as ‘AVSF myopathy’ as a new clinical entity. However, the features of AVSF myopathy have not been well established. Therefore, to evaluate the clinical features, we reviewed the clinical histories, muscle specimens, and genetic analyses of Japanese patients with AVSF myopathy.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: K. Sugie, H. Komaki, T. Kurashige, D. Kaneda, N. Eura, T. Shiota, Y. Nishimori, N. Iguchi, H. Nanaura, T. Kiriyama, E. Mori, I. Nonaka, I. Nishino Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
We have identified four patients with a childhood/adolescence onset of a myopathy from two unrelated consanguineous families. The patients have a wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures as characteristic features. All patients showed increased levels of serum creatine kinase but no or minor muscle weakness. Mild cardiac manifestations were observed. Light and electron microscopical investigations revealed a structural myopathy with numerous lobulated muscle fibers and considerable myofibrillar alterations with a coarse and irregular intermyofibrillar network.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: C. Hedberg-Oldfors, Supervillin Study Group, Supervillin Study Group Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Chloroquine (CQ) and hydroxychloroquine (HCQ) are used in the treatment of malaria and various connective tissue diseases (CTD). They have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. As patients with CTD may have muscle weakness due to myositis or steroid myopathy, the diagnosis can be missed or delayed. In this retrospective study, we aimed to define the clinical phenotype, laboratory features and treatment outcomes of CQ/HCQ-myopathy.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. Naddaf, P. Pritikanta Source Type: research

New genes in neuromuscular diseases
Disrupting pathogenic variants in RNA-binding proteins such as TDP-43, hnRNPA2B1, FUS, TIA-1 are known to cause a spectrum of diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, inclusion body myopathy, and/or distal myopathy. Using deep clinical phenotyping and exome sequencing, we identified six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: P. Mohassel, S. Donkervoort, H. Kim, A. Foley, X. Lornage, hnRNPA2B1 Study Group, N. Foulds, S. Hammans, T. Haack, J. B öhm, M. Tarnopolsky, V. Straub, J. Laporte, F. Muntoni, J. Taylor, C. Bönnemann Source Type: research

New genes in neuromuscular diseases
Distal myopathies are a clinically, histopathologically and genetically heterogeneous group of inherited skeletal muscle diseases with muscle weakness predominantly observed in the distal muscles. Despite advancements in high throughput sequencing, a number of patients remain without a molecular diagnosis. Especially sporadic distal myopathy cases, often due to lack of additional family history, usually cannot progress beyond candidate gene approaches. Taking advantage of deep phenotyping and histopathological evidence, we have identified the small muscle protein X gene (SMPX) as a novel disease gene causing the first X-li...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Johari, M. Savarese, A. Vihola, M. Jokela, A. Torella, G. Piluso, P. Jonson, H. Luque, A. Magot, F. Magri, C. Kornblum, T. Stojkovic, N. Romero, P. Lahermo, K. Donner, V. Nigro, P. Hackman, B. Udd Source Type: research

Limb girdle muscular dystrophies
Dysferlinopathies represent several pathologies caused by mutations in the DYSF gene. The two main phenotypes are Limb-girdle muscular dystrophy (LGMD) type 2B and distal Miyoshi's myopathy, but a proximodistal phenotype accounts for 6-35% of dysferlinopathies. The Acadians were French colonists who settled in the Canadian Maritimes and incurred the Great Deportation. Those who eluded capture remained mostly along the Maritime coastlines, preluding a higher regional prevalence of some recessive diseases.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Bourque, D. Bourcier, J. Mamelona, J. Urtizberea, B. Brais, N. Crapoulet, A. Marrero Source Type: research

Congenital myopathies 2
Titin related disorder is an emerging genetic disorder that is not well described. New phenotypes are being described with improvement in diagnostic genetic testing. We are presenting a 16-year-old Indian boy with congenital static myopathy, complete ophthalmoplegia, thoracolumbar scoliosis and obstructive sleep apnea. His investigations were significant for abnormal muscle magnetic resonance imaging with severe involvement of the gluteal, anterior compartment muscle and clear adductor sparing. His muscle biopsy of right vastus lateralis showed multi-minicores and distinctive cap-like structures.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: H. Qashqari, H. Gonorazky, K. Amburgey, G. Yoon, L. Hazrati, J. Dowling Source Type: research

Congenital myopathies 2
Myotubular myopathy (MTM) is a devastating childhood muscle disease associated with severe disabilities and early death. Maani et al (2018)., recently identified tamoxifen as a novel therapeutic candidate for MTM that improves muscle structure, strength and prolongs survival in MTM mice through modulation of dynamin-2 (DNM2), a known disease modifier. As clinical trials for tamoxifen in MTM are imminent, there remains a need for a reliable, non-invasive biomarker to reflect disease severity and treatment response, facilitating disease monitoring and testing of novel therapies.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: N. Maani, N. Sabha, D. Gustafson, A. Ramani, J. Fish, M. Alexander, J. Dowling Source Type: research

Congenital myopathies 2
RYR1-related myopathy (RYR1-RM) is a frequent diagnosis among congenital myopathies associated with dominant and recessive inheritance. Genetic diagnosis is essential to characterize the clinical spectrum and patients ’ follow-up. To describe the phenotypic, genotypic and muscle MRI (WBMRI) in a series of patients diagnosed with RYR1-RM in a single neuromuscular center. We performed a retrospective study of patients with a genetic diagnosis of RYR1-RM, IRB-approved. Demographic data and patients characteristics were obtained from medical records.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Jofre, B. Suarez, M. Martinez-Jalilie, M. Diemer, C. Hervias, G. Calcagno, X. Ortega, M. Palomino, X. Villanueva, S. Haro, S. Lillo, T. Vial, F. Fattori, E. Bertini, C. Castiglioni Source Type: research

Congenital myopathies 2
A new dog model was generated with a genetic background based on a DNM2 mutation identified in a male Border Collie. The heterozygous R465W mutation of the DNM2 gene is known in humans to be responsible for a form of centronuclear myopathy (CNM). Pups developed from zygotes obtained after fertilization of Beagle oocytes with spermatozoa from the affected Border Collie. The outbred nature and the large size of the dogs contribute to their added value because they help better predict safety of translated treatments.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: Y. Fromes, I. Barth élémy, L. Tiret, J. Boisserie, J. Le Louër, H. Reyngoudt, B. Marty Source Type: research

Congenital myopathies 2
X-linked myotubular myopathy (XLMTM) is a rare congenital neuromuscular disorder affecting boys at a rate of 1 in 50,000 live births. The majority ( ∼80%) of the affected children are born with serious and diffuse skeletal muscle weakness and hypotonia that necessitate immediate and sustained extensive care including tracheostomy and feeding by gastric intubation. Considerable proportions (∼25%) of the cases succumb to death within their fir st year of life and the majority do so later due mainly to respiratory failure.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Ghahramani Seno, J. Volpatti, N. Sabha, C. Alper, E. Sarikaya, J. Dowling Source Type: research

Congenital myopathies 2
The kyphoscoliosis peptidase (KY) gene encodes a muscle-specific a Z-disc-associated protein which is specifically expressed in skeletal-, cardiac muscle and CNS. The mutation in the Ky-gene has first been identified in a mouse mutant with progressive muscular dystrophy and thoracolumbar kyphoscoliosis. Since then, only a few cases with myofibrillar myopathy, congenital myopathy and hereditary spastic paraplegia caused by mutation in KY were described. Here, we present two brothers with congenital myopathy with early contractures carrying a novel homozygous missense (ENST00000423778.2) p.Cys243Arg (c.727T>C) mutation in the KY gene.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: H. Durmus, A. Cakar, Y. Parman Source Type: research

Muscle imaging – mri
The impact of muscle MRI in diagnostics of suspected myopathies is still discussed controversially. To further analyze the status of muscle MRI, electromyography (EMG) and muscle biopsy, a total of 191 patients have been included into the study group. Age at inclusion was 52.63 years (range: 18 to 88 years). All patients included into the study received muscle MRI, EMG and muscle biopsy for diagnostic reason and suspected myopathy. In all patients assessed, localization of biopsy and muscle MRI were identical.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: D. Urban, M. Mohamed, A. Ludolph, J. Kassubek, A. Rosenbohm Source Type: research

Limb girdle muscular dystrophies
Dysferlinopathy is an autosomal recessive disease caused by a DYSF (MIM*603009) gene mutation, located on chromosome 2p13. We investigated clinical, laboratory, radiological, pathological, and genetic spectrum of dysferlinopathy in the Korean population. For this study, we reviewed medical records from patients with genetic myopathy from January 2004 to March 2020 at Gangnam Severance Hospital. Then, we identified 86 patients with dysferlinopathy. We analyzed the clinical spectrum of patients with dysferlinopathy FAF, which included sex, age of the diagnosis; the age of the symptom onset; and the presence of motor weakness...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: U. Yun, H. Park, W. Kim, Y. Choi Source Type: research

Limb girdle muscular dystrophies
Anoctamin 5 (ANO5) belongs to the Anoctamin family of transmembrane proteins and has been suggested to play a part in muscle cell membrane fusion and repair. Mutations in the ANO5 gene are a common cause of muscular dystrophy. Little is known about the pathophysiology in ANO5 ‐related muscular dystrophy. The purpose of this study was to investigate whether inflammatory changes are present in patients with ANO5 myopathy by making a systematic histological and MRI-based evaluation of muscles. Muscle biopsies from 24 patients diagnosed with ANO5 myopathy were reviewed.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Holm-Yildiz, N. Witting, K. Kass, T. Khawajazada, T. Krag, J. Vissing Source Type: research

Limb girdle muscular dystrophies
Dysferlin is a protein of approximately 237 kDa predominantly expressed in striated muscle. Mutations in the gene encoding for dysferlin (DYSF) are responsible for various types of rare autosomal recessive muscular dystrophies such as limb girdle muscular dystrophy R2 (formerly LGMD2B) and distal Miyoshi Myopathy. Absence of dysferlin expression assessed by immunoblot of muscle biopsies or CD14+ peripheral blood monocytes is a highly specific diagnostic indicator of disease. CD14+ immunoblot is generally preferred over the muscle biopsy as being a less invasive and more cost-effective assay.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: D. Cox, D. Cox, M. Henderson, V. Straub, R. Barresi Source Type: research

Limb girdle muscular dystrophies
Patients with autosomal recessive LGMD subtype 2 (LGMD2) may experience severe mobility impairments (including loss of ambulation [LOA]). As clinical heterogeneity exists among patients with LGMD, the objective was to synthesize data on the timing of LOA among patients with LGMD2, particularly calpainopathy (LGMD2A), dysferlinopathy (LGMD2B/Miyoshi myopathy [MM]), and sarcoglycanopathies (LGMD2C-F). In this systematic review, a study-specific search strategy was implemented in MEDLINE and EMBASE in September 2019.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Cheung, I. Audhya, S. Szabo, M. Harwood, K. Gooch Source Type: research

Limb girdle muscular dystrophies
Dysferlinopathy presents as limb-girdle muscular dystrophy or Miyoshi distal myopathy. Beginning to deteriorate from late teen to early adulthood, the patients lose mobility in a decade or so. We had found a third of our dysferlinopathy patients harbor a homozygous nonsense mutation, while another third of them have a heterozygous nonsense mutation in conjunction with another type of pathogenic mutation. Ataluren is an orally administered nontoxic small-molecular compound, currently approved for nonsense-mediated Duchenne muscular dystrophy.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: K. Seo, Y. Park, D. Kim, J. Shin Source Type: research

Fshd / opmd / myotonic dystrophy
Oculopharyngeal muscular dystrophy (OPMD) is a rare late-onset genetic myopathy, affecting mainly eyelid and pharyngeal muscles leading to ptosis and dysphagia, respectively. OPMD is caused by a mutation in Poly-A Binding Protein Nuclear 1 (PABPN1) gene, that codes for a protein essential for proper mRNA biogenesis in nucleus. Accordingly, mutated PABPN1 in OPMD results in PABPN1 intranuclear aggregates in muscle that sequestrate mRNA and proteins and thus induce a wide range of deleterious consequences on muscle homeostasis (mitochondrial dysfunctions, calcium homeostasis disruption, fibrosis, force impairment, atrophy).
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Boulinguiez, F. Roth, J. Dhiab, M. Bui, T. Evangelista, N. Romero, E. Negroni, J. Lacau St Guily, V. Mouly, G. Butler-Browne, C. Trollet Source Type: research

Fshd / opmd / myotonic dystrophy
We report the case of a seventy-nine years old caucasian patient who presented with rapidly progressive dropping head at age 77 and subtle swallowing troubles one year after. There were no other muscular symptoms. On examination, there was no facial involvement (including ptosis or eye movements limitation), neck extensors were weak (3/5 MRC), there was no segmental weakness, except for a discrete deficit of the finger's extensors (4+/5 MRC).
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Masingue, M. Bisciglia, A. Chanut, C. Labasse, C. Metay, T. Evangelista Source Type: research

Congenital muscular dystrophies
In this study, we stratified the phenotypes of 121 patients with COL6-RD from Spain (n  = 56) and the US (n = 65) into three categories according to the maximal motor ability achieved: (1) achieved rising from floor only with assistance = Ullrich congenital muscular dystrophy; (2) achieved rising from floor unassisted = intermediate COL6-RD, and (3) achieved stair clim bing (ascending a minimum of four stairs without use of the railing) = Bethlem myopathy.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: D. Natera-de Benito, A. Reghan-Foley, C. Dom ínguez-González, C. Ortez, M. Jain, A. Mebrahtu, S. Donkervoort, Y. Hu, M. Fink, P. Yun, T. Ogata, J. Medina, J. Díaz-Manera, L. Carrera-García, J. Expósito-Escudero, M. Olivé, J. Colomer, C. Jiménez-Mal Source Type: research

Congenital muscular dystrophies
We report the clinical and molecular findings in 14 patients from 12 families carrying the COL6A3 missense variant c.7447A>G combined with a nonsense, deletion or frameshift COL6A3 mutation and one c.7447A>G homozygous patient.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: R. Villar Quiles, S. Donkevoort, A. de Becdelievre, V. Allamand, V. Jobic, J. Urtizberea, G. Sole, A. Furby, M. Cerino, E. Campana-Salort, A. Magot, A. Ferreiro, B. Eymard, C. B önnemann, P. Richard, C. Metay, T. Stojkovic Source Type: research

Congenital muscular dystrophies
We describe the phenotype, genotype and muscle MRI (WBMRI) in a series of patients with Collagen VI-Related Myopathy (COLVI-RM). A retrospective study of patients with a genetic diagnosis of Collagen-VI-RM, IRB-approved. Demographic data and patients ’ characteristics were obtained from medical records.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: B. Suarez, J. Jofre, M. Martinez-Jalilie, M. Diemer, X. Ortega, T. Vial, S. Lillo, M. Haro, G. Calcagno, M. Palomino, C. Hervias, C. Castiglioni Source Type: research

From the spinal cord to the muscle
Limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MM) are progressive, inherited muscular dystrophies caused DYSF gene mutations. LGMDR2 describes a predominantly proximal phenotype while an MM phenotype involves more distal weakness. It is not clear, for the purposes of clinical trials and drug licencing, if patients with each diagnosis should be separated or can be managed as one disease. The aim of this investigation was to determine if MM and LGMDR2 are distinct clinical entities that require separation for clinical trials.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: U. Moore, H. Gordish, J. D íaz Maneraz, M. James, A. Mayhew, M. Guglieri, S. Spuler, J. Day, K. Jones, D. Bharucha-Goebel, E. Salort-Campana, A. Pestronk, M. Walter, C. Paradas, T. Stojkovic, M. Yoshimura, E. Bravver, E. Pegoraro, J. Mendell, V. Straub Source Type: research

Registries, care, quality of life, management of nmd
Improvements in medical care for patients with genetic muscle diseases have made their lifespan longer. It should be important to provide multidisciplinary child-to-adult transition for better life of them. We reviewed medical records of patients with genetic muscle diseases who visited our clinic for transition between November 2012 and October 2016, and analyzed current status and issues of child-to-adult healthcare transition. We accepted 31 patients with muscular dystrophy and 4 with congenital myopathy for transition in 4 years; mean age was 19.3 ±4.6 years (range 11-32).
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: K. Ogata, T. Murakami, K. Yatabe, M. Suzuki, I. Nonaka, T. Tamura Source Type: research

New genes and diseases / ngs & related techniques
We report 16 patients from a cohort of 585 genotyped congenital myopathy patients whose whole exome sequencing (WES) results along with RNA sequencing (RNA-seq) revealed mutations in uncommon myopathy genes.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Aykanat, C. Genetti, W. Win, Z. Valivullah, E. O'Heir, B. Darras, R. Laine, A. O'Donnell-Luria, A. Beggs Source Type: research

Mitochondrial diseases & metabolic myopathies
We report here four additional patients (P1-P4), from three kindreds, including two sisters (P1, P2) with homozygous or compound heterozygous mid-domain variants in RBCK1.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: R. Phadke, C. Hedberg-Oldfors, R. Scalco, D. Lowe, M. Ashworth, M. Novelli, R. Vara, A. Merwick, H. Amer, R. Sofat, M. Sugarman, A. Jovanovic, M. Roberts, V. Nakou, A. King, I. Bodi, H. Jungbluth, A. Oldfors, E. Murphy Source Type: research

Mitochondrial diseases & metabolic myopathies
TK2d is an ultra-rare genetic mitochondrial disease caused by a critical enzyme deficiency in the mitochondrial DNA (mtDNA) replication pathway leading to mtDNA copy number depletion. TK2d presents as severe progressive myopathy across all ages and leads to significant morbidity (loss of ambulation, need for ventilatory support) and mortality. MT1621 is a fixed dose combination of deoxycytidine (dC) and thymidine (dT) being developed as a substrate enhancement therapy for TK2d. A mechanism of action study was conducted to assess the incorporation of isotopically labeled heavy dC and dT into mtDNA of the knock-out TK2-/- mouse model.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: L. Tsuruda, D. Kenny, C. Bl ázquez-Bermejo, A. Karlsson, R. Martí, Y. Cámara Source Type: research

Late breaking news e-poster presentation
Skeletal muscle-targeted therapies that increase contractility hold promise for the treatment of neuromuscular diseases. As a compound class, fast skeletal muscle troponin activators (FSTAs) directly increase muscle calcium (Ca ²+) sensitivity and amplify the muscle force response to subtetanic neural stimulation. Disease-modifying therapies like systemic gene transfer have previously been shown to improve muscle function in a canine model of myotubular myopathy. The purpose of the current study was to evaluate the expand ed utility of a canine skeletal muscle model to understand the pharmacokinetic/pharmacodynamic (PK/PD...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: Dr. Robert W Grange, Dr. Eva R Chin, Dr. Jordan Klaiman, Dr. Darren Hwee, Dr. Bradley Morgan, Dr. Fady Malik, Dr. Martin Childers, Dr. SiWei Luo, Dr. David Mack Source Type: research

Unusual Skin Involvement in Statin-induced Anti-HMGCR Immune-mediated Necrotizing Myopathy.
PMID: 32985673 [PubMed - as supplied by publisher]
Source: Acta Dermato-Venereologica - September 28, 2020 Category: Dermatology Authors: Scard C, Bara-Passot C, Chassain K, Maillard H Tags: Acta Derm Venereol Source Type: research

Anti-HMGCR Myopathy: A Rare and Serious Side Effect of Statins
Cardiovascular disease is a leading cause of morbidity and mortality in the United States. Since their initial discovery, statins have become the first-line treatment for decreasing the risk of cardiovascular disease. Although they are typically well tolerated, side effects do occur and tend to affect the musculature. Most side effects are benign and resolve after discontinuing the statin. A subset of immune-mediated necrotizing myositis, anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) myopathy is a rare disease that occurs in 0.9 to 1.4 cases per 100,000 people. It causes significant muscle weakness that does...
Source: Journal of the American Board of Family Medicine - September 28, 2020 Category: Primary Care Authors: Irvine, N. J. Tags: Brief Reports Source Type: research

PCSK9 Inhibitors May Lower Cholesterol in Patients with Statin-Associated Immune-Mediated Necrotizing Myopathy
A 2019 study demonstrated the benefit of a newer drug class, PCSK9 inhibitors, to help lower cholesterol in patients with statin-associated immune-mediated necrotizing myopathy...
Source: The Rheumatologist - September 23, 2020 Category: Rheumatology Authors: Vanessa Caceres Tags: Drug Updates Arthritis & Rheumatology cholesterol immune-mediated necrotizing myopathy PCSK9 inhibitors protein convertase subtilisin/kexin type 9 inhibitors statin-associated myopathy Source Type: research