A5026051663- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Inflammatory Myopathies and Dermatomyositis
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- Nuclear Structure and Function
- Cellular Mechanics and Interactions
- Skin and Cellular Biology Research
- Hereditary Neurological Disorders
- Glycogen Storage Diseases and Myoclonus
- Muscle and Compartmental Disorders
- Metabolism and Genetic Disorders
- Peripheral Neuropathies and Disorders
- Biotin and Related Studies
- Eosinophilic Disorders and Syndromes
- Ion channel regulation and function
- Neurological and metabolic disorders
- ATP Synthase and ATPases Research
- Myasthenia Gravis and Thymoma
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Glaucoma and retinal disorders
- Amyotrophic Lateral Sclerosis Research
- Endoplasmic Reticulum Stress and Disease
University Hospital Bonn
2014-2025
Klinik und Poliklinik für Neurologie
2020-2025
University of Bonn
2012-2022
Wellcome Centre for Mitochondrial Research
2017
Newcastle University
2017
Life & Brain (Germany)
2010-2017
Leibniz Institute for Analytical Sciences - ISAS
2017
Centre for Life
2017
RWTH Aachen University
2013-2017
Jülich Aachen Research Alliance
2013
Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Because accompanying inflammation may interact with promote neurodegeneration, anti-inflammatory treatment strategies are being evaluated. peroxisome proliferator-activated receptor γ (PPARγ) agonists act as potent drugs, we tested whether superoxide dismutase (SOD1)-G93A transgenic mice, mouse model ALS, benefit from oral PPARγ agonist...
Objective: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) order to identify characteristic patterns alterations that may be helpful separate these genetic heterogeneous muscular disorders. Methods: Muscle and clinical 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 αB-crystallinopathy, 3 ZASPopathy). The data collected retrospectively 43 prospectively patients. Results: In the semitendinosus was at least...
Mutations in the valosin-containing protein (VCP, p97) gene on chromosome 9p13-p12 cause a late-onset form of autosomal dominant inclusion body myopathy associated with Paget disease bone and frontotemporal dementia (IBMPFD). We report pathological consequences three heterozygous VCP (R93C, R155H, R155C) mutations human striated muscle. IBMPFD skeletal muscle pathology is characterized by degenerative changes filamentous VCP- ubiquitin-positive cytoplasmic nuclear aggregates. Furthermore,...
Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG) dynamics and autophagic protein degradation that underlie the pathogenesis a spectrum degenerative diseases affect muscle, brain, bone. Specifically, identical mutations in adaptor SQSTM1 can cause varied penetrance 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease bone, distal myopathy. It has been hypothesized clinical pleiotropy relates to additional genetic...
Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients disorders as formulated during 259th ENMC Workshop Anaesthesia Disorders.International experts field (paediatric) anaesthesia, neurology, and genetics were invited participate...
Abstract Mutations in the sarcomeric protein titin, encoded by TTN , are emerging as a common cause of myopathies. The diagnosis -related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and prevalence variants control populations. Here, we present combined clinico-pathological, genetic biophysical approach pathogenicity ascertainment missense variants. We identified 30 patients primary congenital (CM) two truncating variants, or one...
To report the retinal phenotype and associated genetic systemic findings in patients with mitochondrial disease. Retrospective case series. Twenty-three retinopathy disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes deafness (MIDD), encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, retinitis pigmentosa (NARP) other manifestations. Review of notes, imaging, electrophysiologic...
Mutations of the human plectin gene (Plec1) cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). Here, we report on molecular mechanisms leading to severe dystrophic muscle alterations in EBS-MD. Analysis a 25-yr-old EBS-MD patient carrying novel homozygous 16-bp insertion mutation (13803ins16/13803ins16) close intermediate filament (IF) binding site showed disorganization myogenic IF cytoskeleton. Intermyofibrillar and subsarcolemmal accumulations...
Mutations of the human valosin-containing protein gene cause autosomal-dominant inclusion body myopathy associated with Paget disease bone and frontotemporal dementia. We identified strumpellin as a novel binding partner. Strumpellin mutations have been shown to hereditary spastic paraplegia. demonstrate that is ubiquitously expressed present in cytosolic endoplasmic reticulum cell fractions. Overexpression or ablation wild-type caused significantly reduced wound closure velocities healing...
Abstract Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and usually caused by mutations proteins required for assembly complex. Mutations nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting leukodystrophy severe epilepsy, we identified homozygous splice site mutation COX8A, which codes ubiquitously expressed isoform subunit VIII, smallest complex IV. The mutation, affecting...
In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair movement, leading arthrogryposis multiplex congenita (AMC). Fetal AChR have also been implicated in apparently rare, milder myopathic presentations termed inactivation syndrome (FARIS). The full spectrum associated with fAChR is still poorly understood. Moreover, since some mothers no myasthenic symptoms, condition likely underreported, resulting failure implement effective...
Mutations in the gene encoding dysferlin cause limb girdle muscular dystrophy type 2B (LGMD2B), distal Miyoshi myopathy (MM), and a rare form of anterior compartment myopathy. To study correlations between clinical manifestations muscle imaging changes we conducted 3.0-T magnetic resonance (MRI) six German patients with primary dysferlinopathies defined by absence expression (MM, n = 3; LGMD2B, 2; hyperCKemia without symptoms, 1).Patients manifest had widespread pathology. In analogy to...
Mutations in the TPM2 gene, which encodes β-tropomyosin, are an established cause of several congenital skeletal myopathies and distal arthrogryposis. We have identified a mutation, p.K7del, five unrelated families with nemaline myopathy consistent distinctive clinical phenotype. Patients develop large joint contractures during childhood, followed by slowly progressive muscle weakness adulthood. The p.K7del mutation results loss highly conserved lysine residue near N-terminus is predicted to...
The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported in a few cases. We performed retrospective multi-centre cohort study focussing on the patients with MH or RM (1987–2017). All muscle biopsies were reviewed by neuromuscular pathologist. Additional morphometric electron microscopic analysis where possible. Through six participating centres we identified 50 from 46 families,...
The elucidation of pathomechanisms leading to the manifestation rare (genetically caused) neurological diseases including neuromuscular (NMD) represents an important step toward understanding genesis respective disease and might help define starting points for (new) therapeutic intervention concepts. However, these "discovery studies" are often limited by availability human biomaterial. Moreover, given that results next-generation-sequencing approaches frequently result in identification...