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1. Superparamagnetic dwell times and tuning of switching rates in perpendicular CoFeB/MgO/CoFeB tunnel junctions

Author

Reiss, G., Ludwig, J., and Rott, K.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Materials Science, Physics - Data Analysis, Statistics and Probability
Abstract

Thin electrodes of magnetic tunnel junctions can show superparamagnetism at surprisingly low temperature. We analysed their thermally induced switching for varying temperature, magnetic and electric field. Although the dwell times follow an Arrhenius law, they are orders of magnitude too small compared to a model of single domain activation. Including entropic effects removes this inconsistency and leads to a magnetic activation volume much smaller than that of the electrode. Comparing data for varying barrier thickness then allows to separate the impact of Zeman energy, spin-transfer-torque and voltage induced anisotropy change on the dwell times. Based on these results, we demonstrate a tuning of the switching rates by combining magnetic and electric fields, which opens a path for their application in noisy neural networks.

Published
2019

2. Magneto-thermoelectric figure of merit of Co/Cu multilayers

Author

Hu, X. K., Krzysteczko, P., Liebing, N., Serrano-Guisan, S., Rott, K., Reiss, G., Kimling, J., Böhnert, T., Nielsch, K., and Schumacher, H. W.

Subjects
Condensed Matter - Materials Science
Abstract

The switching of the magnetization configurations of giant magnetoresistance multilayer stacks not only changes the electric and thermal conductivities, but also the thermopower. We study the magnetotransport and the magneto-thermoelectric properties of Co/Cu multilayer devices in a lateral thermal gradient. We derive values of the Seebeck coefficient, the thermoelectric figure of merit, and the thermoelectric power factor. The Seebeck coefficient reaches values up to -18 microvolt/K at room temperature and shows a magnetic field dependence up to 28.6 % upon spin reversal. In combination with thermal conductivity data of the same Co/Cu stack, we find a spin dependence of the thermoelectric figure of merit of up to 65 %. Furthermore, a spin dependence of the power factor of up to 110 % is derived., Comment: 15 pages, 3 figures

Published
2013
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3. Determination of spin-dependent Seebeck coefficients of CoFeB/MgO/CoFeB magnetic tunnel junction nanopillars

Author

Liebing, N., Serrano-Guisan, S., Rott, K., Reiss, G., Langer, J., Ocker, B., and Schumacher, H. W.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Materials Science
Abstract

We investigate the spin-dependent Seebeck coefficient and the tunneling magneto thermopower of CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJ) in the presence of thermal gradients across the MTJ. Thermal gradients are generated by an electric heater on top of the nanopillars. The thermo power voltage across the MTJ is found to scale linearly with the heating power and reveals similar field dependence as the tunnel magnetoresistance. The amplitude of the thermal gradient is derived from calibration measurements in combination with finite element simulations of the heat flux. Based on this, large spin-dependent Seebeck coefficients of the order of (240 \pm 110) \muV/K are derived. From additional measurements on MTJs after dielectric breakdown, a tunneling magneto thermopower up to 90% can be derived for 1.5 nm MgO based MTJ nanopillars.

Published
2011
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4. Tunneling magneto thermo power in magnetic tunnel junction nanopillars

Author

Liebing, N., Serrano-Guisan, S., Rott, K., Reiss, G., Langer, J., Ocker, B., and Schumacher, H. W.

Subjects
Condensed Matter - Materials Science, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We study the tunneling magneto thermo power (TMTP) in CoFeB/MgO/CoFeB magnetic tunnel junction nanopillars. Thermal gradients across the junctions are generated by a micropatterned electric heater line. Thermo power voltages up to a few tens of \muV between the top and bottom contact of the nanopillars are measured which scale linearly with the applied heating power and hence with the applied temperature gradient. The thermo power signal varies by up to 10 \muV upon reversal of the relative magnetic configuration of the two CoFeB layers from parallel to antiparallel. This signal change corresponds to a large spin-dependent Seebeck coefficient of the order of 100 \muV/K and a large TMTP change of the tunnel junction of up to 90%., Comment: Revised version containing additional data and analyis. 13 pages, 3 figures

Published
2011
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5. Biased quasi ballistic spin torque magnetization reversal

Author

Serrano-Guisan, S., Rott, K., Reiss, G., Langer, J., Ocker, B., and Schumacher, H. W.

Subjects
Condensed Matter - Materials Science
Abstract

We explore the fundamental time limit of ultra fast spin torque induced magnetization reversal of a magnetic memory cell. Spin torque precession during a spin torque current pulse and free precessional magnetization ringing after spin torque pulse excitation is detected by time resolved magneto transport. Adapting the duration of the spin torque excitation pulse to the spin torque precession period allows suppression of the magnetization ringing and thus coherent control of the final orientation of the magnetization. In the presence of a hard axis bias field such coherent control enables an optimum ultra fast, quasi ballistic spin torque magnetization reversal by a single precessional turn directly from the initial to the reversed equilibrium state., Comment: 13 pages 3 Figures

Published
2008
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6. Low-frequency noise and tunnelling magnetoresistance in Fe(110)/MgO(111)/Fe(110) epitaxial magnetic tunnel junctions

Author

Guerrero, R., Aliev, F. G., Villar, R., Hauch, J., Fraune, M., Guntherodt, G., Rott, K., Bruckl, H., and Reiss, G.

Subjects
Condensed Matter - Other Condensed Matter
Abstract

We report on tunnelling magnetoresistance (TMR), current-voltage (IV) characteristics and low frequency noise in epitaxially grown Fe(110)/MgO(111)/Fe(110) magnetic tunnel junctions (MTJs) with dimensions from 2x2 to 20x20 um2. The evaluated MgO energy barrier (0.50+/-0.08 eV), the barrier width (13.1+/-0.5 angstrom) as well as the resistance times area product (7+/-1 Mohmsum2) show relatively small variation, confirming a high quality epitaxy and uniformity of all MTJs studied. The noise power, though exhibiting large variation, was observed to be roughly anticorrelated with the TMR. Surprisingly, for the largest junctions we observed a strong enhancement of the normalized low-frequency noise in the antiparallel magnetic configuration. This behaviour could be related to an interplay between the magnetic state and the local barrier defects structure of the epitaxial MTJs, Comment: 9 pages and 3 figures

Published
2006
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19. Magnetic vortex core reversal by excitation with short bursts of an alternating field

Author

Van Waeyenberge, B., Puzic, A., Stoll, H., Chou, K. W., Tyliszczak, T., Hertel, R., Fahnle, M., Bruckl, H., Rott, K., Reiss, G., Neudecker, I., Weiss, D., Back, C. H., and Schutz, G.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): B. Van Waeyenberge [1, 2]; A. Puzic [1]; H. Stoll (corresponding author) [1]; K. W. Chou [1]; T. Tyliszczak [3]; R. Hertel [4]; M. Fähnle [1]; H. Brückl [5, [...]

Published
2006
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22. Nanotechnology for neuronal ion channels

Author

Lehmann-Horn, F. and Jurkat-Rott, K.

Subjects
Health, Psychology and mental health
Abstract

Ion channels provide the basis for the regulation of electrical excitability in the central and peripheral nervous systems. This review deals with the techniques that make the study of structure [...]

Published
2003

35. Vortex dynamics in Co-Fe-B magnetic tunnel junctions in presence of defects.

Author

Kuepferling, M., Zullino, S., Sola, A., Van de Wiele, B., Durin, G., Pasquale, M., Rott, K., Reiss, G., and Bertotti, G.

Subjects
MAGNETIC tunnelling, MICROMAGNETICS, ACTIVATION energy, ANALYTICAL mechanics, MAGNETISM
Abstract

We investigate the frequency of thermally excited vortex oscillations in Co-Fe-B magnetic tunnel junction (MTJ) pillars in the presence of defects. Under a variable in-plane magnetic field, a characteristic behavior is observed: the frequency oscillates from a maximum at certain field values to a steep minimum, which tends towards zero frequency. These frequency variations are described qualitatively well by an analytical model based on the Thiele equation taking into account a single Gaussian pinning potential. It is thus possible to calculate the in-plane depinning field for certain pinning potential parameters. For steep potentials, the depinning is hysteretic and jumps between the pinned and unpinned regime occur due to the presence of an energy barrier. A sharp frequency minimum occurs at an applied field, where a large flat region in the energy landscape is present. From the experiments, the pinning potentials are estimated to be between -0.2eV and -0.4eV. We also perform micromagnetic simulations of the vortex oscillations in the presence of a distribution of pinning centers. The simulations confirm the validity of the Thiele-approach showing that the vortex remains sufficiently rigid. [ABSTRACT FROM AUTHOR]

Published
2015
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37. OrphanAnesthesia: Handlungsempfehlungen zur Anästhesie bei Mitochondriopathien Morbus Hurler.

Author

Hoppe, K., Plunien, R., Lehmann-Horn, F., Jurkat-Rott, K., Gösele, M., Klingler, W., Stelzner, J., and Terboven, T.

Abstract

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2021

38. Magnetic cobalt nanocrystals organized in patches and chains

Author

Sudfeld, D., Wojczykowski, K., Hachmann, W., Heitmann, S., Rott, K., Hempel, T., Kammerer, S., Jutzi, P., Hutten, A., and Reiss, G.

Subjects
Magnetism -- Research, Cobalt -- Usage, Electron microscopy -- Usage, Magnetic materials -- Research, Superlattices as materials -- Research, Ferromagnetism -- Research, Business, Electronics, Electronics and electrical industries
Abstract

Co nanocrystals have been prepared via two different chemical preparation routes. Microstructural characterization has been carried out by conventional and high-resolution transmission electron microscopy. Magnetic characterization reveals that Co nanocrystais with mean particle size distributions about 6 nm are ferromagnetic at room temperature. Superlattices of about 1 [micro]m x 1 [micro]m can be reproduced. For the second preparation route the formation of an [epsilon]-Co phase was detected by X-ray diffraction. Whereas the pure Co nanocrystals form domains with a mixture of simple cubic and hexagonal packing, FeCo alloyed nanoparticles form long chain-like structures. Index Terms--Arrays, electron microscopy, magnetic materials, nanocluster, superlattices.

Published
2002

39. Myotonia permanens with Nav1.4-G1306E displays varied phenotypes during course of life

Author

Lehmann-Horn, F., D Amico, A., Enrico Bertini, Lomonaco, M., Merlini, L., Nelson, K. R., Philippi, H., Siciliano, G., Spaans, F., and Jurkat-Rott, K.

Subjects
Adult, Male, Heterozygote, Adolescent, Myotonia Congenita, Laryngismus, Respiratory Tract Diseases, Action Potentials, muscular and respiratory tract diseases, Young Adult, Humans, NAV1.4 Voltage-Gated Sodium Channel, Preschool, Child, Exercise, Respiratory Sounds, Voltage-Gated Sodium Channel Blockers, neonate, stridor, Age Factors, Child, Preschool, Dyspnea, Female, Flecainide, Hypertrophy, Infant, Infant, Newborn, Middle Aged, Muscle Weakness, Mutation, Phenotype, Newborn, Original Article
Abstract

Myotonia permanens due to Nav1.4-G1306E is a rare sodium channelopathy with potentially life-threatening respiratory complications. Our goal was to study phenotypic variability throughout life.Clinical neurophysiology and genetic analysis were performed. Using existing functional expression data we determined the sodium window by integration.In 10 unrelated patients who were believed to have epilepsy, respiratory disease or Schwartz-Jampel syndrome, we made the same prima facie diagnosis and detected the same heterologous Nav1.4-G1306E channel mutation as for our first myotonia permanens patient published in 1993. Eight mutations were de-novo, two were inherited from the affected parent each. Seven patients improved with age, one had a benign phenotype from birth, and two died of respiratory complications. The clinical features age-dependently varied with severe neonatal episodic laryngospasm in childhood and myotonia throughout life. Weakness of varying degrees was present. The responses to cold, exercise and warm-up were different for lower than for upper extremities. Spontaneous membrane depolarization increased frequency and decreased size of action potentials; self-generated repolarization did the opposite. The overlapping of steady-state activation and inactivation curves generated a 3.1-fold window area for G1306E vs. normal channels.Residue G1306 Neonatal laryngospasm and unusual distribution of myotonia, muscle hypertrophy, and weakness encourage direct search for the G1306E mutation, a hotspot for de-novo mutations. Successful therapy with the sodium channel blocker flecainide is due to stabilization of the inactivated state and special effectiveness for enlarged window currents. Our G1306E collection is the first genetically clarified case series from newborn period to adulthood and therefore helpful for counselling.

Published
2017

42. Submicron-sized magnetic tunnel junctions in field programmable logic gate arrays.

Author

Meyners, D., Rott, K., Brückl, H., Reiss, G., and Wecker, J.

Subjects
*GATE array circuits, *LITHOGRAPHY, *TUNNELS, *MAGNETICS, *ELECTRICAL engineering, *MINING engineering
Abstract

We experimentally demonstrate the feasibility of reprogrammable logic gate arrays with lateral dimensions down to 10×10 μm2. The gates are based on magnetic tunnel junctions which are elliptically patterned by e-beam lithography with sizes down to 200×100 nm2. The junctions are realized with different tunneling systems and are investigated magnetically and electrically, where the magnetization reversal of the junctions’ soft magnetic layer is done via currents in conducting lines. The switching currents could be reduced by a factor of about 2 by introducing an additional NiFe layer on top of the lines. Thus it is possible to use these gate arrays within a highly integrated environment. [ABSTRACT FROM AUTHOR]

Published
2006
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43. Large Supramolecular Structures of 33-mer Gliadin Peptide Activate Toll-like Receptors in Macrophages

Author

Pizzuto, Malvina, Herrera, Maria Georgina, Lonez, Caroline Elodie, Rott, K, Hutten, Andreas, Sewald, Norbert, Ruysschaert, Jean Marie, Dodero, Verõnica Isabel, Pizzuto, Malvina, Herrera, Maria Georgina, Lonez, Caroline Elodie, Rott, K, Hutten, Andreas, Sewald, Norbert, Ruysschaert, Jean Marie, and Dodero, Verõnica Isabel

Abstract

Gliadin, an immunogenic protein present in wheat, is not fully degraded by humans and after the normal gastric and pancreatic digestion, the immunodominant 33-mer gliadin peptide remains unprocessed. The 33-mer gliadin peptide is found in human faeces and urine, proving not only its proteolytic resistance in vivo but more importantly its transport through the entire human body. Here, we demonstrate that 33-mer supramolecular structures larger than 220 nm induce the overexpression of nuclear factor kappa B (NF-κB) via a specific Toll-like Receptor (TLR) 2 and (TLR) 4 dependent pathway and the secretion of pro-inflammatory cytokines such as IP-10/CXCL10 and TNF-α. Using helium ion microscopy, we elucidated the initial stages of oligomerisation of 33-mer gliadin peptide, showing that rod-like oligomers are nucleation sites for protofilament formation. The relevance of the 33-mer supramolecular structures in the early stages of the disease is paving new perspectives in the understanding of gluten-related disorders., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

46. A novel N440K sodium channel mutation causes myotonia with exercise-induced weakness - exclusion of CLCN1 exon deletion/duplication by MLPA

Author

Lehmann-Horn, F., Orth, M., Kuhn, M., and Jurkat-Rott, K.

Subjects
musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Myotonia Congenita, Hyperkinesis, sodium channel myotonia, Severity of Illness Index, Sodium Channels, Segmental Duplications, Genomic, Chloride Channels, Humans, Paralysis, Muscle, Skeletal, Sequence Deletion, Muscle Weakness, Original Articles, chloride channel myotonia Thomsen and Becker, nervous system diseases, paramyotonia congenita, MLPA, Pedigree, body regions, Acetazolamide, potassiumaggravated myotonia, CLCN1, Hyperkalemia, Anticonvulsants, hyperkalemic periodic paralysis, Anti-Arrhythmia Agents
Abstract

We report a 4-generation Turkish family with 10 affected members presenting with myotonia and potassium- and exercise-induced paralytic attacks. The clinical presentation was neither typical for the chloride channel myotonias Thomsen and Becker nor for the separate sodium channel myotonia entities potassium-aggravated myotonia, paramyotonia congenita, and hyperkalemic periodic paralysis. It is best described by a combination of potassium-aggravated myotonia and hyperkalemic periodic paralysis. We excluded exonic chloride channel mutations including CLCN1 exon deletion/duplication by MLPA. Instead we identified a novel p.N440K sodium channel mutation that is located at the inner end of segment S6 of repeat I. We discuss the genotype phenotype relation.

Published
2011

47. State of the art in hereditary muscle channelopathies

Author

Jurkat-Rott, K. and Lehmann-Horn, F.

Subjects
susceptibility to malignant hyperthermia, Myasthenic Syndromes, Congenital, Original Articles, periodic paralyses, Congenital myasthenic syndromes, Myotonia, Paralyses, Familial Periodic, non-dystrophic myotonias, Drug Therapy, Humans, Channelopathies, Anesthetics, Local, Diuretics, central core disease, Anti-Arrhythmia Agents
Abstract

A combination of electrophysiological and genetic studies has resulted in the identification of several skeletal muscle disorders to be caused by pathologically functioning ion channels and has led to the term channelopathies. Typical hereditary muscle channelopa thies are congenital myasthenic syndromes, non-dystrophic myotonias, periodic paralyses, malignant hyperthermia, and central core disease. Most muscle channelopathies are commonly considered to be benign diseases. However, life-threatening weakness episodes or progressive permanent weakness may make these diseases severe, particularly the periodic paralyses (PP). Even in the typical PP forms characterized by episodic occurrence of weakness, up to 60% of the patients suffer from permanent weakness and myopathy with age. In addition, some PP patients present with a predominant progressive muscle weakness phenotype. The weakness can be explained by strongly depolarized fibers that take up sodium and water and that are electrically inexcitable. Drugs that repolarize the fiber membrane can restore muscle strength and may prevent progression.

Published
2010

48. A novel Ile1455Thr variant in the skeletal muscle sodium channel alpha-subunit in a patient with a severe adult-onset proximal myopathy with electrical myotonia and a patient with mild paramyotonia phenotype

Author

Bednarz, M., Stunnenberg, B.C., Kusters, B., Kamsteeg, E.J., Saris, C.G.J., Groome, J., Winston, V., Meola, G., Jurkat-Rott, K., Voermans, N.C., Bednarz, M., Stunnenberg, B.C., Kusters, B., Kamsteeg, E.J., Saris, C.G.J., Groome, J., Winston, V., Meola, G., Jurkat-Rott, K., and Voermans, N.C.

Abstract

Item does not contain fulltext, In sodium channelopathies, a severe fixed myopathy caused by a dominant mutation is rare. We describe two unrelated patients with a novel variant, p.Ile1455Thr, with phenotypes of paramyotonia in one case and fixed proximal myopathy with latent myotonia in another. In-vitro whole cell patch-clamp studies show that the mutation slows inactivation and accelerates recovery, in line with other paramyotonia variants with destabilized fast inactivation as pathomechanism. Additionally, p.IleI1455 causes a loss-of-function by reduced membrane insertion, right-shift of activation, and slowed kinetics. Molecular dynamics simulations comparing wild type and mutant Nav1.4 showed that threonine substitution hindered D4S4 mobility in response to membrane depolarization, consistent with effects of the mutation on channel inactivation. The fixed myopathy is likely to be associated to gain-of-function leading to sodium accumulation, regional edema, T-tubular swelling and mitochondrial stress. A possible contribution of the loss-of-function features towards myotonia and myopathy is discussed.

Published
2017

49. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes

Author

Schubert, J., Siekierska, A., Langlois, M., May, P., Huneau, C., Becker, F., Muhle, H., Suls, A., Lemke, J. R., de Kovel, C. G. F., Thiele, H., Konrad, K., Kawalia, A., Toliat, M. R., Sander, T., Ruschendorf, F., Caliebe, A., Nagel, I., Kohl, B., Kecskes, A., Jacmin, M., Hardies, K., Weckhuysen, S., Riesch, E., Dorn, T., Brilstra, E. H., Baulac, S., Moller, R. S., Hjalgrim, H., Koeleman, B. P. C., Jurkat-Rott, K., Lehman-Horn, F., Roach, J. C., Glusman, G., Hood, L., Galas, D. J., Martin, B., de Witte, P. A. M., Biskup, S., De Jonghe, P., Helbig, I., Balling, R., Nurnberg, P., Crawford, A. D., Esguerra, C. V., Weber, Y. G., Lerche, H., Euro, Epinomics R. E. S. Consortium, EuroEPINOMICS RES Consortium, [GIN] Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg [Luxembourg], Institute for Systems Biology [Seattle] (ISB), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurogenetics Group, Institut für Humangenetik, Universität Heidelberg [Heidelberg], Cologne Center for Genomics (CCG), University of Cologne, Department of Molecular and Developmental Genetics (VIB11), Flanders institute of biotechnology, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical Genetics Laboratory, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratory of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences Lueven Belgium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Center for Genomics and Transcriptomics (CEGAT), Antwerp University Hospital [Edegem] (UZA), Children’s Hospital of Philadelphia (CHOP ), Cologne Center for Genomics, University of Cologne, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Heidelberg [Heidelberg] = Heidelberg University, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Genetic Linkage, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Syntaxin 1, medicine.disease_cause, Epilepsy/genetics, Cohort Studies, Epilepsy, 0302 clinical medicine, Syntaxin 1/genetics, Missense mutation, Exome, ComputingMilieux_MISCELLANEOUS, In Situ Hybridization, Fluorescence, Zebrafish, Genetics, 0303 health sciences, Mutation, Comparative Genomic Hybridization, Temperature, PAROXYSMAL KINESIGENIC DYSKINESIA SYNAPTIC VESICLE FUSION DE-NOVO MUTATIONS FEBRILE SEIZURES INFANTILE CONVULSIONS GENERALIZED EPILEPSY PRRT2 MUTATIONS GENERATION DISORDERS ZEBRAFISH, Pedigree, Phenotype, Codon, Nonsense, Female, Molecular Sequence Data, Biology, Polymorphism, Single Nucleotide, Seizures, Febrile, 03 medical and health sciences, SCN1B, medicine, Animals, Humans, Amino Acid Sequence, Seizures, Febrile/genetics, Generalized epilepsy, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Sequence Analysis, DNA, Paroxysmal dyskinesia, medicine.disease, Epilepsy syndromes, Human medicine, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Gene Deletion
Abstract

Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B(6), that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees(7,8) identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

Published
2014
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