RT Journal Article
T1 Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.
A1 Schiava, Marianela
A1 Ikenaga, Chiseko
A1 Villar-Quiles, Rocío Nur
A1 Caballero-Ávila, Marta
A1 Topf, Ana
A1 Nishino, Ichizo
A1 Kimonis, Virginia
A1 Udd, Bjarne
A1 Schoser, Benedikt
A1 Zanoteli, Edmar
A1 Souza, Paulo Victor Sgobbi
A1 Tasca, Giorgio
A1 Lloyd, Thomas
A1 Lopez-de Munain, Adolfo
A1 Paradas, Carmen
A1 Pegoraro, Elena
A1 Nadaj-Pakleza, Aleksandra
A1 De Bleecker, Jan
A1 Badrising, Umesh
A1 Alonso-Jiménez, Alicia
A1 Kostera-Pruszczyk, Anna
A1 Miralles, Francesc
A1 Shin, Jin-Hong
A1 Bevilacqua, Jorge Alfredo
A1 Olivé, Montse
A1 Vorgerd, Matthias
A1 Kley, Rudi
A1 Brady, Stefen
A1 Williams, Timothy
A1 Domínguez-González, Cristina
A1 Papadimas, George K
A1 Warman-Chardon, Jodi
A1 Claeys, Kristl G
A1 de Visser, Marianne
A1 Muelas, Nuria
A1 LaForet, Pascal
A1 Malfatti, Edoardo
A1 Alfano, Lindsay N
A1 Nair, Sruthi S
A1 Manousakis, Georgios
A1 Kushlaf, Hani A
A1 Harms, Matthew B
A1 Nance, Christopher
A1 Ramos-Fransi, Alba
A1 Rodolico, Carmelo
A1 Hewamadduma, Channa
A1 Cetin, Hakan
A1 García-García, Jorge
A1 Pál, Endre
A1 Farrugia, Maria Elena
A1 Lamont, Phillipa J
A1 Quinn, Colin
A1 Nedkova-Hristova, Velina
A1 Peric, Stojan
A1 Luo, Sushan
A1 Oldfors, Anders
A1 Taylor, Kate
A1 Ralston, Stuart
A1 Stojkovic, Tanya
A1 Weihl, Conrad
A1 Diaz-Manera, Jordi
A1 VCP International Study Group, 
A1 VCP International Study Group, 
K1 FRONTOTEMPORAL DEMENTIA
K1 GENETICS
K1 INCL BODY MYOSITIS
K1 MUSCLE DISEASE
K1 MYOPATHY
AB 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.
YR 2022
FD 2022-07-27
LK http://hdl.handle.net/10668/20162
UL http://hdl.handle.net/10668/20162
LA en
DS RISalud
RD May 10, 2025