Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.

Autor:	Schiava M; John Walton Muscular Dystrophy Research Centre, Newcastle University, and Newcastle Hospitals NHS Foundation Trusts, Newcastle Upon Tyne, UK., Ikenaga C; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Villar-Quiles RN; APHP, Centre de référence des maladies neuromusculaires, Institut de Myologie, Sorbonne Université, APHP, Hôpital Pitié-Salpêtrière, Paris, France., Caballero-Ávila M; Neuromuscular Disorders Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Topf A; Newcastle University and Newcastle Hospitals NHS Foundation Trusts, Newcastle University, Newcastle upon Tyne, UK., Nishino I; Department of Neuromuscular Research, National Institute of Neuroscience National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan., Kimonis V; Department of Pediatrics Division of Genetics and Genomic Medicine, University of California-Irvine Medical Center Children's Hospital of Orange County, Orange, California, USA., Udd B; Tampere Neuromuscular Center, Tampere University Hospital, Tampere, Finland.; Folkhalsan Genetic Institute, Helsinki University, Helsinki, Finland., Schoser B; Department of Neurology, Friedrich-Baur-Institute Ludwig Maximilian University Clinics, Munich, Germany., Zanoteli E; Department of Neurology, School of Medicine, Universidade de São Paulo (FMUSP), São Paulo, Brazil., Souza PVS; Disciplina de Neurologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Tasca G; Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A Gemelli, IRCCS, Rome, Italy., Lloyd T; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Lopez-de Munain A; Biodonostia Neurosciences Area Group of Neuromuscular Diseases Biodonostia-Osakidetza Basque Health Service, San Sebastian, Spain., Paradas C; Neurology Department, Neuromuscular Disorders Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain.; Instituto de Biomedicina de Sevilla, Sevilla, Spain.; Center for Biomedical Network Research on Neurodegenerative Disorders (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain., Pegoraro E; Department of Neurosciences, University of Padova, Padova, Italy., Nadaj-Pakleza A; Department of Neurology, Centre de Reference des Maldies Neuromusculaires Nord-Est-Ile de France, University Hospital of Strasbourg, Strasbourg, France., De Bleecker J; Department of Neurology and Neuromuscular Reference Center, Ghent University Hospital, Ghent, Belgium., Badrising U; Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands., Alonso-Jiménez A; Department of Neurology, Neuromuscular Reference Centre, Antwerp University Hospital, Universiteit Antwerpen, Instituut Born Bunge, Antwerpen, Belgium., Kostera-Pruszczyk A; Department of Neurology, Medical University of Warsaw, European Reference Network ERN-NMD, Warsaw, Poland., Miralles F; Department of Neurology, Unitat de Patologia Neuromuscular i Gabinet d'electrodiagnòstic, Hospital Universitari Son Espases, Palma de Mallorca, Spain., Shin JH; Laboratory of Molecular Neurology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea., Bevilacqua JA; Unidad Neuromuscular, Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago de Chile, Chile.; Departamento de Neurología y Neurocirugía Clínica, Clínica Dávila, Santiago Chile, Chile., Olivé M; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Deaprtment of Neurology, Neuromuscular Disorders Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain., Vorgerd M; Heimer Institut for Muscle Research, Klinikum Bergmannsheil, Ruhr University, Bochum, Germany., Kley R; Department of Neurology and Clinical Neurophysiology, St Marien-Hospital Borken, Borken, Germany., Brady S; Neurology Department, John Radcliffe Hospital, Oxford, UK., Williams T; Newcastle Motor Neurone Disease Care Centre, Royal Victoria Infirmary, Newcastle, UK., Domínguez-González C; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain.; Neurology Service, Hospital Universitario 12 de Octubre, Madrid, Spain., Papadimas GK; First Department of Neurology, Medical School, Eginition Hospital and National and Kapodistrian University of Athens, Athens, Greece., Warman-Chardon J; Department of Medicine, Ottawa Neuromuscular Centre, Ottawa Hospital, Ottawa, Ontario, Canada., Claeys KG; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.; KU Leuven Laboratory for Muscle Diseases and Neuropathies, Leuven, Belgium., de Visser M; Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands., Muelas N; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain.; Neuromuscular Unit, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain., LaForet P; Neurology department, Raymond-Poincaré hospital, APHP, UVSQ, Paris-Saclay University, Paris, France., Malfatti E; APHP, Neuromuscular Reference Center Nord-Est-Ile-de-France, Henri Mondor Hospital, Université Paris Est, U955, INSERM, Créteil, IMRB, Paris, France., Alfano LN; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA., Nair SS; Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India., Manousakis G; Department of Neurology, University of Minnesota Hospital, Minneapolis, Minnesota, USA., Kushlaf HA; Department of Neurology & Rehabilitation Medicine, University of Cincinnati, Cincinnati, Ohio, USA., Harms MB; NewYork Presbyterian Columbia University Irving Medical Centre, New York, New York, USA., Nance C; Department of Neurology, Carver College of Medicine at the University of Iowa, Iowa, Iowa, USA., Ramos-Fransi A; Neuromuscular Unit, Neurology Department, Hospital Germas Trias i Pujol, Badalona, Spain., Rodolico C; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy., Hewamadduma C; Sheffield Institute for translational neurosciences (SITRAN), Neuroscience Institute, University of Sheffield, Sheffield, UK., Cetin H; Department of Neurology, Medical University of Vienna, Vienna, Austria., García-García J; Neurology Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain., Pál E; Department of Neurology, University of Pécs, Pécs, Hungary., Farrugia ME; Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK., Lamont PJ; Department of Neurology, Royal Perth Hospital, Perth, Western Australia, Australia., Quinn C; Neuromuscular Division, Neurology Department, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Nedkova-Hristova V; Neurology Department, Bellvitge University Hospital, Bellvitge, Spain., Peric S; Neurology Clinic, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Luo S; Department of Neurology, Huashan Hospital Fudan University, Shanghai, China.; National Center for Neurological Disorders, Shanghai, China., Oldfors A; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Taylor K; Southern General Hospital, Glasgow, UK., Ralston S; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK., Stojkovic T; APHP, Centre de référence des maladies neuromusculaires, Institut de Myologie, Sorbonne Université, APHP, Hôpital Pitié-Salpêtrière, Paris, France., Weihl C; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA., Diaz-Manera J
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2022 Jul 27. Date of Electronic Publication: 2022 Jul 27.
DOI:	10.1136/jnnp-2022-328921
Abstrakt:	Background: Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations. Methods: Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. Results: Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8±9.6 years and mean age of onset 45.6±9.3 years. Mean diagnostic delay was 7.7±6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8±7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC <70% and being a full-time wheelchair user were associated with death. Conclusion: This study expands the knowledge on the phenotypic presentation, natural history, genotype-phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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