نتائج البحث - "Peter Van den Bergh"

1

دورية أكاديمية

Human skeletal myopathy myosin mutations disrupt myosin head sequestration

المؤلفون: Glenn Carrington, Abbi Hau, Sarah Kosta, Hannah F. Dugdale, Francesco Muntoni, Adele D’Amico, Peter Van den Bergh, Norma B. Romero, Edoardo Malfatti, Juan Jesus Vilchez, Anders Oldfors, Sander Pajusalu, Katrin Õunap, Marta Giralt-Pujol, Edmar Zanoteli, Kenneth S. Campbell, Hiroyuki Iwamoto, Michelle Peckham, Julien Ochala

المصدر: JCI Insight, Vol 8, Iss 21 (2023)

مصطلحات موضوعية: Muscle biology, Medicine

الوصف: Myosin heavy chains encoded by MYH7 and MYH2 are abundant in human skeletal muscle and important for muscle contraction. However, it is unclear how mutations in these genes disrupt myosin structure and function leading to skeletal muscle myopathies termed myosinopathies. Here, we used multiple approaches to analyze the effects of common MYH7 and MYH2 mutations in the light meromyosin (LMM) region of myosin. Analyses of expressed and purified MYH7 and MYH2 LMM mutant proteins combined with in silico modeling showed that myosin coiled coil structure and packing of filaments in vitro are commonly disrupted. Using muscle biopsies from patients and fluorescent ATP analog chase protocols to estimate the proportion of myosin heads that were super-relaxed, together with x-ray diffraction measurements to estimate myosin head order, we found that basal myosin ATP consumption was increased and the myosin super-relaxed state was decreased in vivo. In addition, myofiber mechanics experiments to investigate contractile function showed that myofiber contractility was not affected. These findings indicate that the structural remodeling associated with LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help design future therapies for myosinopathies.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/59ff4fd339fd4cbaa9a588a2470f9192Test

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النص الكامل

2

دورية أكاديمية

Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation

المصدر: JCI Insight, Vol 6, Iss 14 (2021)

مصطلحات موضوعية: Genetics, Neuroscience, Medicine

الوصف: Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G304Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/47cf72fa59a4478a90634b78aa5718fdTest

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النص الكامل

3

دورية أكاديمية

Detection of variants in dystroglycanopathy-associated genes through the application of targeted whole-exome sequencing analysis to a large cohort of patients with unexplained limb-girdle muscle weakness

المصدر: Skeletal Muscle, Vol 8, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: Whole-exome sequencing, Dystroglycanopathies, Limb-girdle muscle weakness, Diseases of the musculoskeletal system, RC925-935

الوصف: Abstract Background Dystroglycanopathies are a clinically and genetically heterogeneous group of disorders that are typically characterised by limb-girdle muscle weakness. Mutations in 18 different genes have been associated with dystroglycanopathies, the encoded proteins of which typically modulate the binding of α-dystroglycan to extracellular matrix ligands by altering its glycosylation. This results in a disruption of the structural integrity of the myocyte, ultimately leading to muscle degeneration. Methods Deep phenotypic information was gathered using the PhenoTips online software for 1001 patients with unexplained limb-girdle muscle weakness from 43 different centres across 21 European and Middle Eastern countries. Whole-exome sequencing with at least 250 ng DNA was completed using an Illumina exome capture and a 38 Mb baited target. Genes known to be associated with dystroglycanopathies were analysed for disease-causing variants. Results Suspected pathogenic variants were detected in DPM3, ISPD, POMT1 and FKTN in one patient each, in POMK in two patients, in GMPPB in three patients, in FKRP in eight patients and in POMT2 in ten patients. This indicated a frequency of 2.7% for the disease group within the cohort of 1001 patients with unexplained limb-girdle muscle weakness. The phenotypes of the 27 patients were highly variable, yet with a fundamental presentation of proximal muscle weakness and elevated serum creatine kinase. Conclusions Overall, we have identified 27 patients with suspected pathogenic variants in dystroglycanopathy-associated genes. We present evidence for the genetic and phenotypic diversity of the dystroglycanopathies as a disease group, while also highlighting the advantage of incorporating next-generation sequencing into the diagnostic pathway of rare diseases.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13395-018-0170-1Test; https://doaj.org/toc/2044-5040Test

الوصول الحر: https://doaj.org/article/7b793b20033f4da8837130c6461f81e4Test

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النص الكامل

4

دورية أكاديمية

Gait among patients with myotonic dystrophy type 1: A three-dimensional motion analysis study

المؤلفون: Vincent Tiffreau, Christine Detrembleur, Peter Van Den Bergh, Anne Renders, Virginie Kinet, André Thevenon, Etienne Allart, Thierry Lejeune

المصدر: The Journal of the International Society of Physical and Rehabilitation Medicine, Vol 1, Iss 2, Pp 65-71 (2018)

مصطلحات موضوعية: electromyography, gait analysis, kinematics, kinetics, myotonic dystrophy type 1, treadmill, Orthopedic surgery, RD701-811, Medicine

الوصف: Objective: The objective was to characterize the gait abnormalities in myotonic dystrophy type 1 patients. Material and Methods: Outcomes variables were kinematic and kinetic parameters, timing of muscles, mechanical work and energy cost, and the motor function measure. Results: Despite a high cadence and a low ankle range of motion ratio, ankle extension power, and first extension moment of the knee during the stance, the mechanical work and energy cost were normal. The duration of electromyography activation of the gastrocnemius lateralis (GL) muscle was abnormally long. Conclusion: The hypothesis of a myotonic activity of the GL during the swing phase should be investigated.

وصف الملف: electronic resource

العلاقة: http://www.jisprm.org/article.asp?issn=2349-7904;year=2018;volume=1;issue=2;spage=65;epage=71;aulast=TiffreauTest; https://doaj.org/toc/2589-9457Test

الوصول الحر: https://doaj.org/article/c872e31f3eff4be28fdd84e0816886f8Test

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5

دورية أكاديمية

Severe Rhabdomyolysis Associated with Simvastatin and Role of Ciprofloxacin and Amlodipine Coadministration

المؤلفون: Nicolas De Schryver, Xavier Wittebole, Peter Van den Bergh, Vincent Haufroid, Eric Goffin, Philippe Hantson

المصدر: Case Reports in Nephrology, Vol 2015 (2015)

مصطلحات موضوعية: Diseases of the genitourinary system. Urology, RC870-923

الوصف: Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2090-6641Test; https://doaj.org/toc/2090-665XTest

الوصول الحر: https://doaj.org/article/c6aad163512a40a89b8195895be408d9Test

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النص الكامل

6

دورية أكاديمية

Extreme Maternal Metabolic Acidosis Leading to Fetal Distress and Emergency Caesarean Section

المؤلفون: Nicolas Cecere, Corinne Hubinont, Arnauld Kabulu Kadingi, Marie-Françoise Vincent, Peter Van den Bergh, Anna Onnela, Philippe Hantson

المصدر: Case Reports in Obstetrics and Gynecology, Vol 2013 (2013)

مصطلحات موضوعية: Gynecology and obstetrics, RG1-991

الوصف: A 31-year-old pregnant woman ( weeks) was admitted with extreme tachypnea. She had a previous history of congenital muscular dystrophy (Ullrich’s disease) and isolated glucosuria. The patient had reduced food intake during the last 24 hours prior to admission and vomited twice. Serum glucose level was normal (112 mg/dL), while urinalysis revealed glucosuria 4+ and ketonuria 4+. ABG revealed pH 7.06, PCO2 9 mm Hg, and bicarbonate 2 mmol/L. Anion gap was 28 mmol/L. Tachypnea was a compensatory mechanism for a severe nonlactic metabolic acidosis. The diagnosis of starvation ketoacidosis was established. The patient received supplemental dextrose 10% intravenously and sodium bicarbonate. As fetal heart monitoring was pathological, an emergency caesarean section was performed. Umbilical cord venous pH was 7.01, with PCO2 34 mm Hg and bicarbonate 8 mmol/L. Starvation ketoacidosis is a rare metabolic disorder that may occur mainly in the third trimester of pregnancy. Muscular dystrophy and renal glucosuria were precipitating factors.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2090-6684Test; https://doaj.org/toc/2090-6692Test

الوصول الحر: https://doaj.org/article/cdcd997a27944fcfa0889ff508db3162Test

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النص الكامل

7

254th ENMC international workshop. Formation of a European network to initiate a European data collection, along with development and sharing of treatment guidelines for adult SMA patients. Virtual meeting 28 – 30 January 2022

المصدر: Neuromuscular Disorders. 33:511-522

مصطلحات موضوعية: Neurology, Pediatrics, Perinatology and Child Health, Medizin, Neurology (clinical), Genetics (clinical)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::358ba1ce701ca027f0bfab2def0d78b1Test
https://doi.org/10.1016/j.nmd.2023.03.011Test

8

Human light meromyosin mutations linked to skeletal myopathies disrupt the coiled coil structure and myosin head sequestration

المؤلفون: Glenn Carrington, Abbi Hau, Sarah Kosta, Hannah F. Dugdale, Francesco Muntoni, Adele D’Amico, Peter Van den Bergh, Norma B. Romero, Edoardo Malfatti, Juan Jesus Vilchez, Anders Oldfors, Sander Pajusalu, Katrin Õunap, Marta Giralt-Pujol, Edmar Zanoteli, Kenneth S. Campbell, Hiroyuki Iwamoto, Michelle Peckham, Julien Ochala

الوصف: Myosin heavy chains encoded byMYH7andMYH2are among the most abundant proteins in human skeletal muscle. After decades of intense research using a wide range of biophysical and biological approaches, their functions have begun to be elucidated. Despite this, it remains unclear how mutations in these genes and resultant proteins disrupt myosin structure and function, inducing pathological states and skeletal myopathies termed myosinopathies. Here, we have analysed the effects of several commonMYH7andMYH2mutations located in light meromyosin (LMM) using a broad range of approaches. We determined the secondary structure and filament forming capabilities of expressed and purified LMM constructs in vitro, performedin-silicomodelling of LMM constructs, and evaluated the incorporation of eGFP-myosin heavy chain constructs into sarcomeres in cultured myotubes. Using muscle biopsies from patients, we applied Mant-ATP chase protocols to estimate the proportion of myosin heads that were super-relaxed, X-ray diffraction measurements to estimate myosin head order and myofibre mechanics to investigate contractile function. We found that humanMYH7andMYH2LMM mutations commonly disrupt myosin coiled-coil structure and packing of filamentsin vitro; decrease the myosin super-relaxed statein vivoand increase the basal myosin ATP consumption; but are not associated with myofibre contractile deficits. Altogether, these findings indicate that the structural remodelling resulting from LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help in the design of future therapies for myosinopathies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::ab1b4ec646b6b611cfeaf932f88e8f58Test
https://doi.org/10.1101/2023.05.15.540775Test

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The emerging spectrum of foetal acetylcholine receptor antibody-associated disorders (FARAD)

المؤلفون: Nicholas M Allen, Mark O’Rahelly, Bruno Eymard, Mondher Chouchane, Andreas Hahn, Gerry Kearns, Dae-Seong Kim, Shin Yun Byun, Cam-Tu Emilie Nguyen, Ulrike Schara-Schmidt, Heike Kölbel, Adela Della Marina, Christiane Schneider-Gold, Kathryn Roefke, Andrea Thieme, Peter Van den Bergh, Gloria Avalos, Rodrigo Álvarez-Velasco, Daniel Natera-de Benito, Man Hin Mark Cheng, Wing Ki Chan, Hoi Shan Wan, Mary Ann Thomas, Lauren Borch, Julie Lauzon, Cornelia Kornblum, Jens Reimann, Andreas Mueller, Thierry Kuntzer, Fiona Norwood, Sithara Ramdas, Leslie W Jacobson, Xiaobo Jie, Miguel A Fernandez-Garcia, Elizabeth Wraige, Ming Lim, Jean Pierre Lin, Kristl G Claeys, Selma Aktas, Maryam Oskoui, Yael Hacohen, Ameneh Masud, M Isabel Leite, Jacqueline Palace, Darryl De Vivo, Angela Vincent, Heinz Jungbluth

المصدر: Brain.

مصطلحات موضوعية: Neurology (clinical)

الوصف: In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). fAChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicenter cohort (n = 46 cases) associated with maternal fAChR antibodies, 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established MG diagnosis. All mothers (n = 30) had AChR antibodies, and where tested, against the fAChR (binding to fAChR was often much greater than that to the adAChR). Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%) or, during early infancy mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/IVIG/PLEX) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognised and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose Fetal Acetylcholine Receptor Antibody-related Disorder (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognise, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::34284e62cb5632e5fa3d1b50598045ebTest
https://doi.org/10.1093/brain/awad153Test

10

European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases

المساهمون: Repositório da Universidade de Lisboa, Neurology, ANS - Neuroinfection & -inflammation

المصدر: European journal of neurology, 29(6), 1571-1586. Wiley-Blackwell

مصطلحات موضوعية: AGREE, recommendation, consensus, neurology, Practice Guidelines as Topic, Humans, rare diseases, Neurology (clinical), Nervous System Diseases, 610 Medicine & health, Delphi, guideline

الوصف: © 2022 European Academy of Neurology
Background and purpose: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. Methods: A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. Results: The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. Conclusions: This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::656400a6389d2f66ec5d4fad84207509Test
http://www.scopus.com/inward/record.url?scp=85127364547&partnerID=8YFLogxKTest

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