A5074843522- Inflammatory Myopathies and Dermatomyositis
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Eosinophilic Disorders and Syndromes
- Immunodeficiency and Autoimmune Disorders
- Celiac Disease Research and Management
- Peripheral Neuropathies and Disorders
- Systemic Sclerosis and Related Diseases
- Genomics and Rare Diseases
- Myasthenia Gravis and Thymoma
- Muscle activation and electromyography studies
- Cardiomyopathy and Myosin Studies
- Diet and metabolism studies
- Heterotopic Ossification and Related Conditions
- Parkinson's Disease and Spinal Disorders
- Cancer-related gene regulation
- Skin Diseases and Diabetes
- biodegradable polymer synthesis and properties
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
Radboud University Nijmegen
2016-2025
Radboud University Medical Center
2016-2025
Radboud Institute for Molecular Life Sciences
2022-2024
University Medical Center Utrecht
2006-2020
University Medical Center
2018-2020
Amsterdam Neuroscience
2020
University of Amsterdam
2020
Elisabeth-TweeSteden Ziekenhuis
2020
Wageningen University & Research
2019
Leiden University
2018
For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these cause phenotypes. Knowledge of intermediate steps crucial to understand pathogenesis, while also providing leads for potential pharmacological intervention. Here we relied upon natural human variation identify effects on trans-gene expression (expression quantitative trait locus mapping, eQTL) in whole peripheral blood from 1,469 unrelated...
Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility phenotypes sporadic ALS, we performed genome-wide SNP analysis ALS cases controls. A total 288,357 SNPs were screened set 1,821 2,258 controls from U.S. Europe. Survival was using 1,014 deceased cases. Top results for further an independent sample 538 556 rs1541160 KIFAP3...
Abstract Background Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis mainly based on clinical symptoms, there currently no therapy to stop disease or slow its progression. Since access cord tissue not possible at onset, we investigated changes gene expression profiles whole blood ALS patients. Results Our transcriptional study showed dramatic patients; 2,300 probes (9.4%) significant...
In rare diseases it is difficult to achieve high-quality evidence of treatment efficacy because small cohorts and clinical heterogeneity. With emerging treatments for diseases, innovative trial designs are needed.To investigate the effectiveness mexiletine in nondystrophic myotonia using an aggregated N-of-1 trials design compare results between this a previously conducted RCT.A series aggregated, double-blind, randomized, placebo-controlled N-of-1-trials, performed single academic referral...
Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, hereditary sensory neuropathy, or (de novo) dominant mental retardation type 9. More recently, variants have also been described a few cases with paraplegia. Here, we describe 20 24 patients from clinical exome sequencing cohort of 347 individuals mostly 'pure' In these patients, was slowly progressive and pure, but highly variable disease onset (0-57 years). Segregation analyses showed de novo occurrence seven...
Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic antibody status and clinical, serological histopathological features to explore utility of this identify myositis subgroups predict prognosis. Data from various European registries were pooled. Anticytosolic was determined by an established ELISA technique. Cases stratified according...
To investigate the characteristics of different clinico-serologic subgroups immune-mediated necrotizing myopathy (IMNM).We retrospectively reviewed data from medical charts 64 patients diagnosed with IMNM between 2012 and 2017 in 3 neuromuscular referral centers The Netherlands 1 Belgium.Seventeen had anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies (Abs), whom 11 a history statin use, 15 anti-signal recognition particle (SRP) Abs, 2 anti-melanoma...
Diaphragm ultrasound is increasingly used in the diagnosis of diaphragm dysfunction and to guide respiratory management patients with neuromuscular disorders those who are critically ill. However, association between variables demographic factors like age, sex, body mass index (BMI) understudied. Such relationships important for correct interpretation normative values comparison selected groups. The aim this study was determine associations subject characteristics.B-mode image at zone...
Mutations in the m.13094T>C MT-ND5 gene have been previously described three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at time analysis (median age death was 10 years (range: 5·4 months−37 years, IQR = 17·9 years). Nine manifested with LS, one mitochondrial encephalomyopathy, lactic acidosis stroke-like episodes (MELAS), Leber...
The biological pathways involved in amyotrophic lateral sclerosis (ALS) remain elusive and diagnostic decision-making can be challenging. Gene expression studies are valuable overcoming such challenges since they shed light on differentially regulated may ultimately identify biomarkers. This two-stage transcriptome-wide study, including 397 ALS patients 645 control subjects, identified 2,943 expressed transcripts predominantly RNA binding intracellular transport. When batch effects between...
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of connective tissue diseases, collectively known as myositis. Diagnosis IIM is challenging while timely recognition an utter importance considering treatment options and otherwise irreversible (severe) long-term clinical complications. With the EULAR/ACR classification criteria (2017) considerable advancement has been made in diagnostic workup IIM. While these take into account parameters well presence one autoantibody,...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase susceptibility. In contrast, rare copy-number (CNVs), been associated with neuropsychiatric traits, not studied for ALS well-powered study populations. To examine role of CNVs susceptibility, we conducted CNV including over 19 000 individuals. screen 1875...
Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS considered to be complex trait genome-wide association studies (GWAS) have implicated few susceptibility loci. However, many more causal loci remain discovered. Since it has been shown that genetic variants associated with traits are likely eQTLs than frequency-matched from GWAS platforms, we conducted two-stage screening for ALS. In addition, applied an...
Neuromuscular disorders (NMDs) are clinically and genetically heterogeneous. Accurate molecular genetic diagnosis can improve clinical management, provides appropriate counseling testing of relatives, allows potential therapeutic trials.To establish the utility panel-based whole exome sequencing (WES) in NMDs a population with children adults various neuromuscular symptoms.Clinical sequencing, followed by diagnostic interpretation variants genes associated NMDs, was performed cohort 396...
We explored efficacy and safety of IVIg as first-line treatment in patients with an idiopathic inflammatory myopathy.In this investigator-initiated phase 2 open-label study, we included 20 adults a newly diagnosed, biopsy-proven myopathy, disease duration less than 9 months. Patients IBM prior use immunosuppressants were excluded. The standard regimen consisted (Privigen) monotherapy for weeks: loading dose (2 g/kg body weight) two subsequent maintenance doses (1 3-week interval. primary...
<h3>Objective</h3> To validate the diagnostic accuracy of a previously described short sonographic protocol to identify chronic inflammatory neuropathy (CIN), including demyelinating polyneuropathy (CIDP), Lewis Sumner syndrome, and multifocal motor (MMN), determine added value nerve ultrasound detect treatment-responsive patients compared conduction studies (NCS) in prospective multicenter study. <h3>Methods</h3> We included 100 consecutive clinically suspected CIN 3 centers. The study...
Autoantibodies to cytosolic 5'-nucleotidase 1A (cN-1A; NT5C1A) have a high specificity differentiating sporadic inclusion body myositis from polymyositis and dermatomyositis. In primary Sjögren's syndrome (pSS) systemic lupus erythematosus (SLE) anti-cN-1A autoantibodies can be detected as well. However, various frequencies of reactivity been reported in SLE pSS, which may at least part explained by the different assays used. Here, we determined occurrence large number patients with pSS...