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Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.
Schiava, Marianela; Ikenaga, Chiseko; Villar-Quiles, Rocío Nur; Caballero-Ávila, Marta; Topf, Ana; Nishino, Ichizo; Kimonis, Virginia; Udd, Bjarne; Schoser, Benedikt; Zanoteli, Edmar; Souza, Paulo Victor Sgobbi; Tasca, Giorgio; Lloyd, Thomas; Lopez-de Munain, Adolfo; Paradas, Carmen; Pegoraro, Elena; Nadaj-Pakleza, Aleksandra; De Bleecker, Jan; Badrising, Umesh; Alonso-Jiménez, Alicia; Kostera-Pruszczyk, Anna; Miralles, Francesc; Shin, Jin-Hong; Bevilacqua, Jorge Alfredo; Olivé, Montse; Vorgerd, Matthias; Kley, Rudi; Brady, Stefen; Williams, Timothy; Domínguez-González, Cristina; Papadimas, George K; Warman-Chardon, Jodi; Claeys, Kristl G; de Visser, Marianne; Muelas, Nuria; LaForet, Pascal; Malfatti, Edoardo; Alfano, Lindsay N; Nair, Sruthi S; Manousakis, Georgios; Kushlaf, Hani A; Harms, Matthew B; Nance, Christopher; Ramos-Fransi, Alba; Rodolico, Carmelo; Hewamadduma, Channa; Cetin, Hakan; García-García, Jorge; Pál, Endre; Farrugia, Maria Elena.
Afiliação
  • 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.
  • Schoser B; Folkhalsan Genetic Institute, Helsinki University, Helsinki, Finland.
  • Zanoteli E; Department of Neurology, Friedrich-Baur-Institute Ludwig Maximilian University Clinics, Munich, Germany.
  • Souza PVS; Department of Neurology, School of Medicine, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
  • Tasca G; Disciplina de Neurologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
  • Lloyd T; Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A Gemelli, IRCCS, Rome, Italy.
  • Lopez-de Munain A; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Paradas C; Biodonostia Neurosciences Area Group of Neuromuscular Diseases Biodonostia-Osakidetza Basque Health Service, San Sebastian, Spain.
  • Pegoraro E; Neurology Department, Neuromuscular Disorders Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
  • Nadaj-Pakleza A; Instituto de Biomedicina de Sevilla, Sevilla, Spain.
  • De Bleecker J; Center for Biomedical Network Research on Neurodegenerative Disorders (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
  • Badrising U; Department of Neurosciences, University of Padova, Padova, Italy.
  • Alonso-Jiménez A; Department of Neurology, Centre de Reference des Maldies Neuromusculaires Nord-Est-Ile de France, University Hospital of Strasbourg, Strasbourg, France.
  • Kostera-Pruszczyk A; Department of Neurology and Neuromuscular Reference Center, Ghent University Hospital, Ghent, Belgium.
  • Miralles F; Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
  • Shin JH; Department of Neurology, Neuromuscular Reference Centre, Antwerp University Hospital, Universiteit Antwerpen, Instituut Born Bunge, Antwerpen, Belgium.
  • Bevilacqua JA; Department of Neurology, Medical University of Warsaw, European Reference Network ERN-NMD, Warsaw, Poland.
  • Olivé M; Department of Neurology, Unitat de Patologia Neuromuscular i Gabinet d'electrodiagnòstic, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
  • Vorgerd M; Laboratory of Molecular Neurology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
  • Kley R; Unidad Neuromuscular, Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago de Chile, Chile.
  • Brady S; Departamento de Neurología y Neurocirugía Clínica, Clínica Dávila, Santiago Chile, Chile.
  • Williams T; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
  • Domínguez-González C; Deaprtment of Neurology, Neuromuscular Disorders Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Papadimas GK; Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
  • Warman-Chardon J; Heimer Institut for Muscle Research, Klinikum Bergmannsheil, Ruhr University, Bochum, Germany.
  • Claeys KG; Department of Neurology and Clinical Neurophysiology, St Marien-Hospital Borken, Borken, Germany.
  • de Visser M; Neurology Department, John Radcliffe Hospital, Oxford, UK.
  • Muelas N; Newcastle Motor Neurone Disease Care Centre, Royal Victoria Infirmary, Newcastle, UK.
  • LaForet P; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain.
  • Malfatti E; Neurology Service, Hospital Universitario 12 de Octubre, Madrid, Spain.
  • Alfano LN; First Department of Neurology, Medical School, Eginition Hospital and National and Kapodistrian University of Athens, Athens, Greece.
  • Nair SS; Department of Medicine, Ottawa Neuromuscular Centre, Ottawa Hospital, Ottawa, Ontario, Canada.
  • Manousakis G; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
  • Kushlaf HA; KU Leuven Laboratory for Muscle Diseases and Neuropathies, Leuven, Belgium.
  • Harms MB; Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands.
  • Nance C; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain.
  • Ramos-Fransi A; Neuromuscular Unit, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
  • Rodolico C; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
  • Hewamadduma C; Neurology department, Raymond-Poincaré hospital, APHP, UVSQ, Paris-Saclay University, Paris, France.
  • Cetin H; APHP, Neuromuscular Reference Center Nord-Est-Ile-de-France, Henri Mondor Hospital, Université Paris Est, U955, INSERM, Créteil, IMRB, Paris, France.
  • García-García J; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • Pál E; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
  • Farrugia ME; Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
Article em En | MEDLINE | ID: mdl-35896379
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.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Neurol Neurosurg Psychiatry Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Neurol Neurosurg Psychiatry Ano de publicação: 2022 Tipo de documento: Article