%0 Journal Article
%A Schiava, Marianela
%A Ikenaga, Chiseko
%A Villar-Quiles, Rocío Nur
%A Caballero-Ávila, Marta
%A Topf, Ana
%A Nishino, Ichizo
%A Kimonis, Virginia
%A Udd, Bjarne
%A Schoser, Benedikt
%A Zanoteli, Edmar
%A Souza, Paulo Victor Sgobbi
%A Tasca, Giorgio
%A Lloyd, Thomas
%A Lopez-de Munain, Adolfo
%A Paradas, Carmen
%A Pegoraro, Elena
%A Nadaj-Pakleza, Aleksandra
%A De Bleecker, Jan
%A Badrising, Umesh
%A Alonso-Jiménez, Alicia
%A Kostera-Pruszczyk, Anna
%A Miralles, Francesc
%A Shin, Jin-Hong
%A Bevilacqua, Jorge Alfredo
%A Olivé, Montse
%A Vorgerd, Matthias
%A Kley, Rudi
%A Brady, Stefen
%A Williams, Timothy
%A Domínguez-González, Cristina
%A Papadimas, George K
%A Warman-Chardon, Jodi
%A Claeys, Kristl G
%A de Visser, Marianne
%A Muelas, Nuria
%A LaForet, Pascal
%A Malfatti, Edoardo
%A Alfano, Lindsay N
%A Nair, Sruthi S
%A Manousakis, Georgios
%A Kushlaf, Hani A
%A Harms, Matthew B
%A Nance, Christopher
%A Ramos-Fransi, Alba
%A Rodolico, Carmelo
%A Hewamadduma, Channa
%A Cetin, Hakan
%A García-García, Jorge
%A Pál, Endre
%A Farrugia, Maria Elena
%A Lamont, Phillipa J
%A Quinn, Colin
%A Nedkova-Hristova, Velina
%A Peric, Stojan
%A Luo, Sushan
%A Oldfors, Anders
%A Taylor, Kate
%A Ralston, Stuart
%A Stojkovic, Tanya
%A Weihl, Conrad
%A Diaz-Manera, Jordi
%A VCP International Study Group
%A VCP International Study Group
%T Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.
%D 2022
%U http://hdl.handle.net/10668/20162
%X 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. Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. 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 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 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  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.
%K FRONTOTEMPORAL DEMENTIA
%K GENETICS
%K INCL BODY MYOSITIS
%K MUSCLE DISEASE
%K MYOPATHY
%~