2026-04-17T01:42:08Zhttps://recercat.cat/oai/request
oai:recercat.cat:2072/4714662025-05-08T14:47:05Zcom_2072_98col_2072_378192
RECERCAT author Töpf, Ana author Johnson, Katherine author Bates, Adam author Phillips, Lauren author Chao, Katherine Ru-Yui author England, Eleina M. author Laricchia, KristenM. author Mullen, Thomas author Valkanas, Elise author Xu, Liwen author Bertoli, Marta author Blain, Alison author Casasús, Ana B. author Duff, Jennifer author Mroczek, Magdalena author Specht, Sabine author Lek, Monkol author Ensini, Monica author MacArthur, Daniel G. author Akay, Ela author Alonso-Pérez, Jorge author Baets, Jonathan author Barisic, Nina author Bastian, Alexandra author Borell, Sabine author Chamova, Teodora author Claeys, Kristl author Colomer, Jaume author Coppens, Sandra author Deconinck, Nicolas author de Ridder, Willem author Diaz-Manera, Jordi author Domínguez-González, C author Duncan, Alexis author Durmus, Hacer author Fahmy, Nagia A. author Farrugia, Maria Elena author Fernández-Torrón, Roberto author Gonzalez-Quereda, L author Haberlova, Jana author von der Hagen, Maja author Hahn, Andreas author Jakovčević, Antonia author Jericó-Pascual, Ivonne author Kapetanovic, Solange author Kenina, Viktorija author Kirschner, Janbernd author Klein, Andrea author Kölbel, Heike author Kostera-Pruszczyk, Anna author Kulshrestha, Richa author Lähdetie, Jaana author Layegh, Mahsa author Longman, Cheryl author López de Munain, Adolfo author Loscher, Wolfgang author Lusakowska, Anna author Maddison, Paul author Magot, Armelle author Majumdar, Anirban author Martí, Pilar author Martínez Arroyo, Amaia author Mazanec, Radim author Mercier, Sandra author Mongini, Tiziana author Muelas, Nuria author Nascimento, Andrés author Nafissi, Shahriar author Omidi, Shirin author Ortez González, Carlos Ignacio author Paquay, Stéphanie author Pereon, Yann author Perić, Stojan author Ponzalino, Valentina author Rakočević Stojanović, Vidosava author Remiche, Gauthier author Rodríguez Sainz, Aida author Rudnik, Sabine author Sanchez Albisua, Iciar author Santos, Manuela author Schara, Ulrike author Shatillo, Andriy author Sertić, Jadranka author Stephani, Ulrich author Strang-Karlsson, Sonja author Sznajer, Yves author Tanev, Ani author Tournev, Ivailo author Van den Bergh, Peter author Van Parijs, Vinciane author Vílchez, Juan author Vill, Katharina author Vissing, John author Wallgren-Pettersson, Carina author Wanschitz, Julia author Willis, T. A author Witting, Nanna author Zulaica, Miren author Straub, Volker author Universitat Autònoma de Barcelona 2020 Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes. open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. https://creativecommons.org/licenses/by-nc-nd/4.0/ Genetic diagnosis Limb-girdle weakness Neuromuscular disease Next-generation sequencing Targeted exome analysis Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness Article