A5016184915- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Epilepsy research and treatment
- Metabolism and Genetic Disorders
- Myasthenia Gravis and Thymoma
- Corneal surgery and disorders
- Cardiac electrophysiology and arrhythmias
- Genetics and Neurodevelopmental Disorders
- Renal cell carcinoma treatment
- Cellular transport and secretion
- Liver Disease Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Pediatric Hepatobiliary Diseases and Treatments
- Gallbladder and Bile Duct Disorders
- Autoimmune Neurological Disorders and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Neurological and metabolic disorders
- Immunodeficiency and Autoimmune Disorders
- Connective tissue disorders research
- Photoreceptor and optogenetics research
- Biliary and Gastrointestinal Fistulas
- Genomic variations and chromosomal abnormalities
- Mitochondrial Function and Pathology
- Cardiac Arrhythmias and Treatments
Ludwig-Maximilians-Universität München
2015-2024
LMU Klinikum
2018-2024
Institute of Human Genetics
2022
Inserm
2014
Sorbonne Université
2014
University of Geneva
2014
München Klinik
2010
University of Bonn
1996-2006
Life & Brain (Germany)
2006
Hertie Foundation
2006
Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene ( KCNQ2 ) located on was isolated found be expressed in brain. Expression frog Xenopus laevis oocytes led potassium-selective currents that activated slowly depolarization. In large pedigree BFNC, five–base pair insertion would delete more than 300 amino acids from the carboxyl terminus. mutant did...
ABSTRACT Extracellular vesicles (EVs) are intercellular communicators with key functions in physiological and pathological processes have recently garnered interest because of their diagnostic therapeutic potential. The past decade has brought about the development commercialization a wide array methods to isolate EVs from serum. Which subpopulations captured strongly depends on isolation method, which turn determines how suitable resulting samples for various downstream applications. To...
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first, and to date only, idiopathic for which a specific mutation has been found. A missense in critical M2 domain of a4 subunit neuronal nicotinic acetylcholine receptor (CHRNA4) recently identified one large Australian pedigree. Here we describe novel CHRNA4 gene Norwegian family. Three nucleotides (GCT) were inserted at nucleotide position 776 into coding region C-terminal end domain. Physiological investigations...
Abstract We recently reported mutations in the sodium channel gene SCN2A two families with benign familial neonatal‐infantile seizures (BFNISs). Here, we aimed to refine molecular‐clinical correlation of early childhood epilepsies. was analyzed 2 probable BFNIS, 9 possible 10 infantile seizures, and 93 additional various Mutations effecting changes conserved amino acids were found BFNIS families, four nine none others. Our eight had six different mutations; one mutation (R1319Q) occurred...
<h3>Context</h3> Missense mutations in the<i>GABRG2</i>gene, which encodes the γ2 subunit of central nervous γ-aminobutyric acid (GABA)<sub>A</sub>receptors, have recently been described 2 families with idiopathic epilepsy. In one these families, affected individuals predominantly exhibited childhood absence epilepsy and febrile convulsions. <h3>Objective</h3> To assess role of<i>GABRG2</i>in genetic predisposition to epilepsies. <h3>Design</h3> The<i>GABRG2</i>gene was screened by...
KCNQ2 and KCNQ3 are two homologous K + channel subunits that can combine to form heterotetrameric channels with properties of neuronal M channels. Loss-of-function mutations in either subunit lead benign familial neonatal convulsions (BFNC), a generalized, idiopathic epilepsy the newborn. We now describe syndrome which BFNC is followed later life by myokymia, involuntary contractions skeletal muscles. All affected members myokymia/BFNC family carried mutation (R207W) neutralized charged...
One hypothesis proposes that a pre-existing alteration of medial temporal lobe structures contributes to febrile convulsions and subsequent hippocampal sclerosis (HS) in patients with epilepsy (TLE) antecedent convulsions. It is possible such structural does not always lead may also be present clinically unaffected relatives.We tested this by MRI investigation 23 members two families, whom 13 had experienced 10 not. member each family subsequently developed TLE. We compared the right/left...
To study the prevalence of DEPDC5 mutations in a series 30 small European families with phenotype compatible autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).Thirty unrelated referred ADNFLE were recruited France, Italy, Germany, Belgium, and Norway. Whole-exome sequencing was performed 10 probands direct coding sequence 20 probands. Testing for nonsense-mediated messenger RNA decay (NMD) lymphoblastic cells.Exome revealed splice acceptor mutation (c.2355-2A>G) proband German...
Abstract Septic shock is a common medical condition with mortality approaching 50% where early diagnosis and treatment are of particular importance for patient survival. Novel biomarkers that serve as prompt indicators sepsis urgently needed. High‐throughput technologies assessing circulating micro RNA s represent an important tool biomarker identification, but the blood‐compartment specificity these mi has not yet been investigated. We characterized profiles from serum exosomes, total blood...
The α4 subunit of the neuronal nicotinic acetylcholine receptor is first gene shown to be involved in a human idiopathic epileptic disease. A missense mutation, leading replacement serine 248 by phenylalanine second transmembrane segment, had been detected patients with autosomal dominant nocturnal frontal lobe epilepsy. properties wild type composed and β2 subunits mutant where carried mutation at were compared means cDNA manipulation expression Xenopus oocytes. exhibited faster...
Autosomal dominant lateral temporal lobe epilepsy previously has been linked to chromosome 10q22-q24, and recently mutations in the LGI1 gene (Leucine-rich gene, Glioma Inactivated) have found some autosomal families. We now identified a missense mutation affecting conserved cysteine residue extracellular region of protein. The C46R is associated with large Norwegian family showing unusual clinical features like short-lasting sensory aphasia auditory symptoms.
Benign familial neonatal convulsions (BFNC) is a rare dominantly inherited epileptic syndrome characterized by frequent brief seizures within the first days of life. The disease caused mutations in one two recently identified voltage-gated potassium channel genes, KCNQ2 or KCNQ3. Here, we describe four-generation BFNC family carrying novel mutation distal, unconserved C-terminal domain KCNQ2, 1-bp deletion, 2513delG, codon 838 predicting substitution last seven and extension another 56 amino...
Background Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and study interactions between heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, uses extracellular vesicles as an intercellular communication system prepare surrounding tissue for invasive growth. However, little is known about effects culture on vesicles. The aim this was comprehensively characterize organoid models compare them conventional 2D...
Summary: Purpose: The recent linkage between a genetically transmissible form of epilepsy (ADNFLE) and mutations within the α 4 subunit, one component major brain neuronal nicotinic acetylcholine receptor (nAChR), raises question role this in epileptogenesis. Although acting by different mechanisms, two genetic alterations so far identified both render nAChR less efficient. In view high sensitivity ADNFLE to carbamazepine (CBZ), we studied effects drug valproate (VPA) on human β 2 its...
Physiological and pharmacological properties of the human neuronal α4β2 nicotinic AChR mutants found in patients suffering from autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) were studied. Investigations AChRs reconstituted Xenopus oocytes with control or mutated α4 subunits revealed that both mutation S248F as well Leucine insertion (776ins3) result major but different changes physiological receptors. Mutation causes a decrease apparent affinity to ACh about 7 fold. In...
Naturally expressed nicotinic acetylcholine receptors composed of alpha4 and beta2 subunits (alpha4beta2-nAChR) are the predominant form high affinity nicotine binding site in brain implicated reward, mediation cholinergic transmission, modulation signaling through other chemical messages, a number neuropsychiatric disorders. To develop model system for studies human alpha4beta2-nAChR allowing protein chemical, functional, pharmacological, regulation expression studies, were stably...
Two novel alternatively spliced isoforms of the human two‐pore‐domain potassium channel TREK‐2 were isolated from cDNA libraries kidney and fetal brain. The cDNAs 2438 base pairs (bp) (TREK‐2b) 2559 bp (TREK‐2c) encode proteins 508 amino acids each. RT‐PCR showed that TREK‐2b is strongly expressed in (primarily proximal tubule) pancreas, whereas TREK‐2c abundantly In situ hybridization revealed a very distinct expression pattern rat brain which partially overlapped with TREK‐1. Expression...