Genotype–phenotype correlations in valosin-containing protein disease: a retrospective muticentre study. Issue 10 (27th July 2022)

• Record Type: Journal Article
• Authors: 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; Lamont, Phillipa J; Quinn, Colin; Nedkova-Hristova, Velina; Peric, Stojan; Luo, Sushan; Oldfors, Anders; Taylor, Kate; Ralston, Stuart; Stojkovic, Tanya; Weihl, Conrad; Diaz-Manera, Jordi;
• Other Names: author non-byline.; Munain Adolfo López de author non-byline.; Ramos-Fransi Alba author non-byline.; Nadaj-Pakleza Aleksandra author non-byline.; Alonso-Jiménez Alicia author non-byline.; Martinez-Piñeiro Alicia author non-byline.; Töpf Ana author non-byline.; Oldfors Anders author non-byline.; Kaminska Anna author non-byline.; Kostera-Pruszczyk Anna author non-byline.; Mayhew Anna author non-byline.; Rydelius Anna author non-byline.; Behin Anthony author non-byline.; Toscano Antonio author non-byline.; Laín Aurelio Hernández author non-byline.; Lannes Beatrice author non-byline.; Velez Beatriz author non-byline.; Schoser Benedikt author non-byline.; Kierdaszuk Biruta author non-byline.; Udd Bjarne author non-byline.; Paepe Boel De author non-byline.; Eymard Bruno author non-byline.; Cazcarra Carla Marco author non-byline.; Rodolico Carmelo author non-byline.; Paradas Carmen author non-byline.; Hedberg-Oldfors Carola author non-byline.; Hewamadduma Channa author non-byline.; Longman Cheryl author non-byline.; Bettollo Chiara Marini author non-byline.; Ikenaga Chiseko author non-byline.; Nance Christopher author non-byline.; Quinn Colin author non-byline.; Weihl Conrad author non-byline.; Papadopoulos Constantinos author non-byline.; Metay Corinne author non-byline.; Domínguez-González Cristina author non-byline.; Hilton-Jones David author non-byline.; Zanotelli Edmar author non-byline.; Malfatti Edoardo author non-byline.; Pegoraro Elena author non-byline.; Harrington Elizabeth A. author non-byline.; Eline Ellen author non-byline.; Gelpi Ellen author non-byline.; Rivas Eloy author non-byline.; Pál Endre author non-byline.; Miralles Francesc author non-byline.; Papadimas George K author non-byline.; Manousakis Gergious author non-byline.; Sorarù Gianni author non-byline.; Tasca Giorgio author non-byline.; Bisogni Giulia author non-byline.; Lucente Giuseppe author non-byline.; Cetin Hakan author non-byline.; Kushlaf Hani author non-byline.; Nishino Ichizo author non-byline.; Bleecker Jan L De author non-byline.; François Jean author non-byline.; Chanson Jean-Baptiste author non-byline.; Lin Jie author non-byline.; Shin Jin-Hong author non-byline.; Warman Jodi author non-byline.; Palmio Johanna author non-byline.; Baets Jonathan author non-byline.; Díaz-Manera Jordi author non-byline.; Bevilacqua Jorge A author non-byline.; Pérez Jorge Alonso author non-byline.; Díaz Jorge author non-byline.; García-García Jorge author non-byline.; Vilchez Juan J author non-byline.; Hudson Judith author non-byline.; Hadzsiev Kinga author non-byline.; Claeys Kristl G author non-byline.; Alfano Lindsay N author non-byline.; Bello Luca author non-byline.; Farrugia Maria Elena author non-byline.; Schiava Marianela author non-byline.; Visser Marianne de author non-byline.; Campero Mario author non-byline.; Sabatelli Mario author non-byline.; Masingue Marion author non-byline.; Caballero-Ávila Marta author non-byline.; Harms Matthew B author non-byline.; Vorgerd Matthias author non-byline.; Monforte Mauro author non-byline.; James Meredith author non-byline.; Guglieri Michela author non-byline.; Inoue Michio author non-byline.; Povedano Mónica author non-byline.; Hofer Monika author non-byline.; Olivé Montse author non-byline.; Garcia-Angarita Natalia author non-byline.; Earle Nicholas author non-byline.; Sarró Noemi Vidal author non-byline.; Muelas Nuria author non-byline.; Lafôret Pascal author non-byline.; Rihard Pascale author non-byline.; Souza Paulo VS author non-byline.; Jonghe Peter de author non-byline.; Lamont Phillipa J. author non-byline.; Riguzzi Pietro author non-byline.; Camaño Pilar author non-byline.; Rubio Raúl Domínguez author non-byline.; Carlier Robert author non-byline.; Muni-Lofra Robert author non-byline.; Fernández-Torrón Roberto author non-byline.; Villar-Quiles Rocío Nur author non-byline.; Alvarez Rodrigo author non-byline.; Kley Rudi author non-byline.; Krause Sabine author non-byline.; Leonard-Louis Sarah author non-byline.; Souvannanorath Sarah author non-byline.; Klotz Sigrid author non-byline.; Thiele Simone author non-byline.; Xirou Sofia author non-byline.; Nair Sruthi S author non-byline.; Brady Stefen author non-byline.; Peric Stojan author non-byline.; Ralston Stuart author non-byline.; Luo Sushan author non-byline.; Stojkovic Tanya author non-byline.; Evangelista Teresinha author non-byline.; Lloyd Thomas E author non-byline.; Grider Tiffany author non-byline.; Williams Timothy author non-byline.; Badrising Umesh author non-byline.; Nedkova-Hristova Velina author non-byline.; Rakocevic-Stojanovic Vidosava author non-byline.; Kimonis Virginia author non-byline.; Straub Volker author non-byline.; Zhu Wenhua author non-byline.; Ridder Willem de author non-byline.; Kelly William author non-byline.; Saito Yoshihiko author non-byline.; Park Young-Eun author non-byline.; Nishimori Yukako author non-byline.; Sahenk Zarife author non-byline.;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93:Issue 10(2022)
• Page Start: 1099
• Page End: 1111
• Publication Date: 2022-07-27
• Subjects: MUSCLE DISEASE -- GENETICS -- MYOPATHY -- INCL BODY MYOSITIS -- FRONTOTEMPORAL DEMENTIA; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-328921
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.