Semantic and right temporal variant of FTD: Next generation sequencing genetic analysis on a single-center cohort.

Autor:	Rossi G; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Salvi E; Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Mehmeti E; Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Ricci M; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Villa C; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Prioni S; Clinical Neuropsychology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Moda F; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Di Fede G; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Tiraboschi P; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Redaelli V; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Coppola C; Department of Advanced Medical and Surgical Sciences, University of Campania 'L. Vanvitelli', Naples, Italy., Koch G; Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy., Canu E; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy., Filippi M; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy.; Unit of Neurorehabilitation, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy., Agosta F; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy., Giaccone G; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Caroppo P; Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in aging neuroscience [Front Aging Neurosci] 2022 Dec 08; Vol. 14, pp. 1085406. Date of Electronic Publication: 2022 Dec 08 (Print Publication: 2022).
DOI:	10.3389/fnagi.2022.1085406
Abstrakt:	Semantic and right temporal variant of frontotemporal dementia (svFTD and rtvFTD) are rare clinical phenotypes in which, in most cases, the underlying pathology is TDP-43 proteinopathy. They are usually sporadic disorders, but recent evidences suggest a higher frequency of genetic mutations for the right temporal versus the semantic variant. However, the genetic basis of these forms is not clear. In this study we performed a genetic screening of a single-center cohort of svFTD and rtvFTD patients, aiming at identifying the associated genetic variants. A panel of 73 dementia candidate genes has been analyzed by NGS target sequencing including both causal and risk/modifier genes in 23 patients (15 svFTD and 8 rtvFTD) and 73 healthy age-matched controls. We first performed a single variant analysis considering rare variants and then a gene-based aggregation analysis to evaluate the cumulative effects of multiple rare variants in a single gene. We found 12 variants in nearly 40% of patients (9/23), described as pathogenic or classified as VUS/likely pathogenic. The overall rate was higher in svFTD than in rtvFTD. Three mutations were located in MAPT gene and single mutations in the following genes: SQSTM1, VCP, PSEN1, TBK1, OPTN, CHCHD10, PRKN, DCTN1 . Our study revealed the presence of variants in genes involved in pathways relevant for the pathology, especially autophagy and inflammation. We suggest that molecular analysis should be performed in all svFTD and rtvFTD patients, to better understand the genotype-phenotype correlation and the pathogenetic mechanisms that could drive the clinical phenotypes in FTD. Competing Interests: EC has received research supports from the Italian Ministry of Health. MF is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). FA is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec, Roche and Zambon; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council and the Foundation Research on Alzheimer Disease. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Rossi, Salvi, Mehmeti, Ricci, Villa, Prioni, Moda, Di Fede, Tiraboschi, Redaelli, Coppola, Koch, Canu, Filippi, Agosta, Giaccone and Caroppo.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu