A5047730908- Muscle Physiology and Disorders
- RNA Research and Splicing
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Epilepsy research and treatment
- Genetics and Neurodevelopmental Disorders
- Neuroblastoma Research and Treatments
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- Glioma Diagnosis and Treatment
- Hereditary Neurological Disorders
- Metabolism and Genetic Disorders
- Tissue Engineering and Regenerative Medicine
- Myasthenia Gravis and Thymoma
- Diet and metabolism studies
- Biotin and Related Studies
- Genomics and Chromatin Dynamics
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- ATP Synthase and ATPases Research
- Telomeres, Telomerase, and Senescence
Humboldt-Universität zu Berlin
2017-2025
Freie Universität Berlin
2017-2025
Charité - Universitätsmedizin Berlin
2014-2025
Helios Hospital Berlin-Buch
2023
Guy's Hospital
2015
St Thomas' Hospital
2015
Ludwig-Maximilians-Universität München
2015
Friedrich Baur Stiftung
2015
The exosome is a conserved multi-protein complex that essential for correct RNA processing. Recessive variants in components EXOSC3, EXOSC8, and RBM7 cause various constellations of pontocerebellar hypoplasia (PCH), spinal muscular atrophy (SMA), central nervous system demyelination. Here, we report on four unrelated affected individuals with recessive EXOSC9 the effect function vitro individuals' fibroblasts skeletal muscle vivo zebrafish. clinical presentation was severe, early-onset,...
Myostatin (Mstn) participates in the regulation of skeletal muscle size and has emerged as a regulator metabolism. Here, we hypothesized that lack myostatin profoundly depresses oxidative phosphorylation-dependent function. Toward this end, explored Mstn(-/-) mice model for constitutive absence AAV-mediated overexpression propeptide blockade adult wild-type mice. We show muscles from mice, although larger stronger, fatigue extremely rapidly. deficiency shifts aerobic toward anaerobic energy...
Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on energy metabolism and energy-dependent function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation by treatment with soluble ActRIIB-Fc triggers extreme fatigability. is associated elevated serum...
Background Very long-chain fatty acids (VLCFAs) are essential for functioning of biological membranes. ELOVL acid elongase 1 catalyses elongation saturated and monounsaturated C22-C26-VLCFAs. We studied two patients with a dominant ELOVL1 mutation. Independently, Kutkowska-Kaźmierczak et al. had investigated the same found extended our study towards additional biochemical, functional, therapeutic aspects. Methods did mutation screening by whole exome sequencing. RNA-sequencing was performed...
Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one-third of cases. Even when a structural lesion identified as the epileptogenic focus, understanding underlying genetic causes crucial to guide both counseling treatment decisions. Both somatic germline DNA variants may contribute itself and/or influence severity symptoms. We therefore used whole exome sequencing (WES) search for potentially pathogenic brain samples from children with lesional epilepsy who...
<h3>Objective:</h3> To identify the cause of sensorimotor neuropathy in a cohort patients with genetically unsolved neuropathies (57 families total 74 members) whom hitherto known disease genes had been excluded. <h3>Methods:</h3> We used autozygosity mapping or haplotype analysis to delineate potential loci informative families. For mutation detection, we either whole-exome sequencing Sanger positional candidates. Subsequently, larger was specifically screened for <i>IGHMBP2</i> mutations....
Various genetic defects cause autism associated with intellectual disability and epilepsy. Here, we set out to identify the defect in a consanguineous Omani family three affected children whom mutations known candidate genes had been excluded beforehand.For mutation screening, combined autozygosity mapping whole exome sequencing. Segregation of potential disease variants phenotype was verified by Sanger A splice-site confirmed quantified qPCR.We found an autosomal recessive splice acceptor...
Dystrophin is a rod-shaped cytoplasmic protein that provides sarcolemmal stability as structural link between the cytoskeleton and extracellular matrix via dystrophin-associated complex (DAPC). Mutations in dystrophin-encoding DMD gene cause X-linked dystrophinopathies with variable phenotypes, most severe being Duchenne muscular dystrophy (DMD) characterized by progressive muscle wasting fibrosis. However, dystrophin deficiency does not only impair function of skeletal heart but may also...
To identify the underlying genetic cause of a congenital neuropathy in 5-year-old boy as part cohort 32 patients from 23 families with genetically unresolved neuropathies.We used autozygosity mapping coupled next-generation sequencing to investigate consanguineous family Lebanon 1 affected and 2 healthy children. Variants were investigated for segregation by Sanger sequencing. A splice site mutation was further evaluated on messenger RNA level quantitative reverse transcription PCR....
Transforming growth factor-β (TGF-β) signalling is thought to contribute the remodelling of extracellular matrix (ECM) skeletal muscle and functional decline in patients with muscular dystrophies. We wanted determine role TGF-β-induced ECM dystrophic muscle.We experimentally induced pathological hallmarks severe dystrophy by mechanically overloading plantaris mice. Furthermore, we determined TGF-β on tissue modulation function (i) myostatin knockout (Mstn-/- ) mice (ii) additional...
Congenital myasthenic syndromes (CMS) are characterized by muscle weakness, ptosis and episodic apnoea. Mutations affect integral protein components of the neuromuscular junction (NMJ). Here we searched for genetic basis CMS in female monozygotic twins.We employed whole-exome sequencing mutation detection Sanger segregation analysis. Immunohistology was done with antibodies against CHD8, rapsyn, β-catenin (βCAT) golgin on fi-bro-blasts, human mouse muscle. We recorded superresolution images...
Background Dmd mdx , harbouring the c.2983C>T nonsense mutation in exon 23, is a mouse model for Duchenne muscular dystrophy (DMD), frequently used to test therapies aimed at dystrophin restoration. Current translational research methodologically hampered by lack of reporter model, which would allow direct visualization expression as well longitudinal vivo studies. Methods We generated EGFP‐mdx allele carrying cis mdx‐ 23 and C‐terminal EGFP‐tag. This allows spontaneously therapeutically...
Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and presence antibodies to metabotropic glutamate 5 receptor (mGluR5). Little known about pathogenetic link between these symptoms role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with isolated quantitative immunocytochemistry for mGluR5-expression. Further, we studied L-1236, L-428, L-540, SUP-HD1, KM-H2, HDLM-2 cell lines FACS Western...
Mutations in SLC25A4 (syn. ANT1, Adenine nucleotide translocase, type 1) are known to cause either autosomal dominant progressive external ophthalmoplegia (adPEO) or recessive mitochondrial myopathy, hypertrophic cardiomyopathy, and lactic acidosis.Whole exome sequencing a young man with subsarcolemmal aggregations, acidosis, L-2-hydroxyglutaric aciduria (L-2-HGA) revealed new homozygous mutation [c.653A>C, NM_001151], leading the replacement of highly conserved glutamine by proline...
Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and presence antibodies to metabotropic glutamate 5 receptor (mGluR5). Little known about pathogenetic link between these symptoms role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with isolated quantitative immunocytochemistry for mGluR5-expression. Further, we studied L-1236, L-428, L-540, SUP-HD1, KM-H2, HDLM-2 cell lines FACS Western...
Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency function mGluR5 HL its potential role causing seropositive disease. We studied representative cohort pediatric NHL (n = 57) using immunohistochemistry fluorescence staining to investigate expression. All tissues...
Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one third of cases. Even when a structural lesion identified as the epileptogenic focus, understanding underlying genetic causes crucial to guide both counseling treatment decisions. Both somatic germline DNA variants may contribute itself and/or influence severity symptoms. We therefore used whole exome sequencing (WES) search for potentially pathogenic brain samples from children with lesional epilepsy who...
Figure S1. Targeting of various dystrophin isoforms in Dmd EGFP mice. A schematic representation known and splice variants their alternative C-termini; mice, the FLAG-EGFP sequence is fused to exon 79 coding Dmd. We expected successful targeting Dp427 (M, B, P), Dp260, Dp140, Dp116, Dp71, Dp71d, Dp71c. The alternatively spliced namely Dp71f, Dp71Δ110, Dp40 contain an C-terminus that does not hence cannot be tagged with EGFP. Dark blue squares show C-terminal generated by skipping 78. Due...