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Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies Orme, Tatiana Hernandez, Dena Ross, Owen A. Kun-Rodrigues, Celia Darwent, Lee Shepherd, Claire E. Parkkinen, Laura Ansorge, Olaf Clark, Lorraine N. Honig, Lawrence S. Marder, Karen Lemstra, Afina W. Rogaeva, Ekaterina St George-Hyslop, Peter Londos, Elisabet Zetterberg, Henrik Morgan, Kevin Troakes, Claire Al-Sarraj, Safa Lashley, Tammaryn Holton, Janice Compta, Yaroslau Deerlin, Vivianna Van Trojanowski, John Q. Serrano, Geidy E. Beach, Thomas G. Lesage, Suzanne Galasko, Douglas Masliah, Eliezer Santana, Isabel Pastor, Pau Tienari, Pentti J. Myllykangas, Liisa Oinas, Minna Revesz, Tamas Lees, Andrew Boeve, Bradley F. Petersen, Ronald C. Ferman, Tanis J. Escott-Price, Valentina Demència amb cossos de Lewy Malalties neurodegeneratives Lewy body dementia Neurodegenerative Diseases Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease. 2020-12-21T16:51:39Z 2020-12-21T16:51:39Z 2020-01-29 2020-12-21T16:51:39Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1186/s40478-020-0879-z Acta Neuropathologica Communications, 2020, num. 8, p. 5 https://doi.org/10.1186/s40478-020-0879-z cc-by (c) Orme, Tatiana et al., 2020 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess BioMed Central Articles publicats en revistes (Medicina)