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Autor
Auer-Grumbach, Michaela 2 Löscher, Wolfgang N 2 Schlotter-Weigel, Beate 2 Seeman, Pavel 2 Abreu, Lisa 1 Baets, Jonathan 1 Baumeister, Maren 1 Beetz, Christian 1 Bonello-Palot, Nathalie 1 Braathen, Geir J 1 Brenner, David 1 Brügger, Britta 1 Carvajal, Alejandra 1 Cassereau, Julien 1 Cui, Guoliang 1 Dalton, Joline 1 Dankwa, Lois 1 De Jonghe, Peter 1 Deconinck, Tine 1 Delmont, Emilien 1
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Pracoviště
Department of Neurology Medical Unive... 2 AP HP Institut de Myologie Centre de ... 1 AP HP Laboratoire de génétique molécu... 1 Abertawe Bro Morgannwg University Hea... 1 Anne Rowling Regenerative Neurology C... 1 Centogene AG Rostock Germany 1 Centre for Medical Research Universit... 1 Centre for Neuromuscular Diseases Nat... 1 Centro para la Investigación Biomédic... 1 Clinical Department of Neurology Medi... 1 Complejo Hospitalario Universitario d... 1 Core Facility Omics IT and Data Manag... 1 DNA Laboratory Department of Child Ne... 1 DNA Laboratory Department of Pediatri... 1 Department of Clinical Chemistry and ... 1 Department of Clinical Neurophysiolog... 1 Department of Clinical Neurosciences ... 1 Department of Clinical and Experiment... 1 Department of Immunology Hospital de ... 1 Department of Medical Genetics Childr... 1
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Autor
Auer-Grumbach, Michaela 2 Löscher, Wolfgang N 2 Schlotter-Weigel, Beate 2 Seeman, Pavel 2 Abreu, Lisa 1 Baets, Jonathan 1 Baumeister, Maren 1 Beetz, Christian 1 Bonello-Palot, Nathalie 1 Braathen, Geir J 1 Brenner, David 1 Brügger, Britta 1 Carvajal, Alejandra 1 Cassereau, Julien 1 Cui, Guoliang 1 Dalton, Joline 1 Dankwa, Lois 1 De Jonghe, Peter 1 Deconinck, Tine 1 Delmont, Emilien 1
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Pracoviště
Department of Neurology Medical Unive... 2 AP HP Institut de Myologie Centre de ... 1 AP HP Laboratoire de génétique molécu... 1 Abertawe Bro Morgannwg University Hea... 1 Anne Rowling Regenerative Neurology C... 1 Centogene AG Rostock Germany 1 Centre for Medical Research Universit... 1 Centre for Neuromuscular Diseases Nat... 1 Centro para la Investigación Biomédic... 1 Clinical Department of Neurology Medi... 1 Complejo Hospitalario Universitario d... 1 Core Facility Omics IT and Data Manag... 1 DNA Laboratory Department of Child Ne... 1 DNA Laboratory Department of Pediatri... 1 Department of Clinical Chemistry and ... 1 Department of Clinical Neurophysiolog... 1 Department of Clinical Neurosciences ... 1 Department of Clinical and Experiment... 1 Department of Immunology Hospital de ... 1 Department of Medical Genetics Childr... 1
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Wolfgang N, Löscher* Dotaz Zobrazit nápovědu
Digitální knihovna NLK
Plný text - Článek
NLK
Cell Press Free Archives
od 1994-04-01 do Před 1 rokem
Free Medical Journals
od 1995 do Před 1 rokem
Elsevier Open Access Journals
od 1995-01-01 do 2023-06-13
Elsevier Open Archive Journals
od 1995-01-01 do Před 1 rokem
PubMed
30952607
DOI
10.1016/j.immuni.2019.03.005
Knihovny.cz E-zdroje
Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8+ T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8+ T cell death. Protective CD8+ T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness.
- MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- cytokiny biosyntéza MeSH
- dědičné senzorické a autonomní neuropatie genetika MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocytární choriomeningitida imunologie virologie MeSH
- mechanistické cílové místo rapamycinového komplexu 1 metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- proliferace buněk MeSH
- serin-C-palmitoyltransferasa genetika MeSH
- sfingolipidy biosyntéza MeSH
- signální transdukce imunologie MeSH
- stres endoplazmatického retikula genetika imunologie MeSH
- virus lymfocytární choriomeningitidy imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
PubMed
33880507
DOI
10.1093/brain/awab014
Knihovny.cz E-zdroje
Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.
- MeSH
- autoantigeny imunologie MeSH
- autoprotilátky imunologie MeSH
- chronická zánětlivá demyelinizační polyneuropatie imunologie MeSH
- dospělí MeSH
- kontaktin 1 imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekuly buněčné adheze neuronové imunologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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Senderek, Jan
Autor Senderek, Jan From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany. michaela.auer-grumbach@meduniwien.ac.at jan.senderek@med.uni-muenchen.de
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Lassuthova, Petra
Autor Lassuthova, Petra From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Kabzińska, Dagmara
Autor Kabzińska, Dagmara From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Abreu, Lisa
Autor Abreu, Lisa From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Baets, Jonathan
Autor Baets, Jonathan From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Beetz, Christian
Autor Beetz, Christian From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Braathen, Geir J
Autor Braathen, Geir J From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Brenner, David
Autor Brenner, David From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Dalton, Joline
Autor Dalton, Joline From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
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Dankwa, Lois
Autor Dankwa, Lois From the Friedrich-Baur-Institute (J.S., B.S.-W., M.W.), Department of Neurology, LMU Munich, Germany DNA Laboratory (P.L., P.S.), Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Czech Republic Neuromuscular Unit (D.K., A.K.), Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Dr. John T. Macdonald Foundation Department of Human Genetics (L.A., A.R., S.Z.), John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, FL Neurogenetics Group (J.B., T.D., P.D.J.), Center for Molecular Neurology, University of Antwerp Institute Born-Bunge (J.B., T.D., P.D.J.), University of Antwerp Neuromuscular Reference Centre (J.B., P.D.J.), Department of Neurology, Antwerp University Hospital, Belgium Department of Clinical Chemistry and Laboratory Medicine (C.B.), Jena University Hospital Centogene AG (C.B.), Rostock, Germany Department of Medical Genetics (G.J.B., H.H.), Telemark Hospital Trust, Skien, Norway Neurology Department (D.B., A.L., J. Weishaupt), Ulm University, Germany Department of Neurology (J.D., D. Walk), University of Minnesota, Minneapolis Department of Neurology (L.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia Department of Sleep Medicine and Neuromuscular Diseases (B.D., A.S., P.Y.), University of Münster Institute of Human Genetics (K.E., I.K.), Medical Faculty, RWTH Aachen University, Germany Sydney Medical School (M.E., M.K., G.N.), Concord Hospital, Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, Australia Department of Orthopaedics and Trauma Surgery (C.F., K.K., D. Weinmann, R.W., S.T., M.A.-G.), Medical University of Vienna, Austria AP-HP (T.S.), Institut de Myologie, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, G-H Pitié-Salpêtrière, Paris, France Department of Neurology (D.N.H.), University of Rochester, NY Department of Clinical Neurosciences (R.H.), University of Cambridge School of Clinical Medicine, UK Department of Neurology (S.I.), Konventhospital der Barmherzigen Brüder Linz Karl Chiari Lab for Orthopaedic Biology (K.K., D. Weinmann, S.T.), Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Austria Stanford Center for Undiagnosed Diseases (J.N.K.), Stanford, CA Undiagnosed Diseases Network (UDN) (J.N.K., S.Z.) Centre for Medical Research (N.G.L., R.O., G.Ravenscroft), University of Western Australia, Nedlands Harry Perkins Institute of Medical Research (N.G.L., R.O., G. Ravenscroft), Nedlands Neurogenetic Unit (P.J.L.), Royal Perth Hospital, Perth, Australia Department of Neurology (W.N.L., J. Wanschitz), Medical University of Innsbruck, Austria Department of Neurosciences and Behavior (W.M.), Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil Department of Neurology (S.P.), Hannover Medical School, Germany Department of Clinical and Experimental Medicine (G. Ricci), University of Pisa, Italy Institute of Human Genetics (S.R.-S.), Medical University of Innsbruck, Austria Department of Neurodegenerative Diseases Hertie-Institute for Clinical Brain Research and Center of Neurology (L.S., R.S., M.S.), University of Tübingen German Center for Neurodegenerative Diseases (DZNE) (L.S., R.S., M.S.), Tübingen, Germany AP-HP (B.F.), Laboratoire de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital de Bicêtre Le Kremlin-Bicêtre, France Institute of Human Genetics (T.M.S.), Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg Institute for Human Genetics (T.M.S.), Technical University Munich and Institut für Klinische Genetik (J. Wagner), Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Germany
OBJECTIVE: To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained neuropathies in the elderly, we performed genetic analysis of 230 patients with unexplained axonal neuropathies and disease onset ≥35 years. METHODS: We recruited patients, collected clinical data, and conducted whole-exome sequencing (WES; n = 126) and MME single-gene sequencing (n = 104). We further queried WES repositories for MME variants and measured blood levels of the MME-encoded protein neprilysin. RESULTS: In the WES cohort, the overall detection rate for assumed disease-causing variants in genes for CMT or other conditions associated with neuropathies was 18.3% (familial cases 26.4%, apparently sporadic cases 12.3%). MME was most frequently involved and accounted for 34.8% of genetically solved cases. The relevance of MME for late-onset neuropathies was further supported by detection of a comparable proportion of cases in an independent patient sample, preponderance of MME variants among patients compared to population frequencies, retrieval of additional late-onset neuropathy patients with MME variants from WES repositories, and low neprilysin levels in patients' blood samples. Transmission of MME variants was often consistent with an incompletely penetrant autosomal-dominant trait and less frequently with autosomal-recessive inheritance. CONCLUSIONS: A detectable fraction of unexplained late-onset axonal neuropathies is genetically determined, by variants in either CMT genes or genes involved in other conditions that affect the peripheral nerves and can mimic a CMT phenotype. MME variants can act as completely penetrant recessive alleles but also confer dominantly inherited susceptibility to axonal neuropathies in an aging population.
- MeSH
- Charcotova-Marieova-Toothova nemoc krev genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- hereditární motorické a senzitivní neuropatie krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- neprilysin krev genetika MeSH
- sekvenování exomu MeSH
- senioři MeSH
- stárnutí * krev MeSH
- věk při počátku nemoci MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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