{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:34:42Z","timestamp":1783571682681,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","award":["PATHWAYS-200-059"],"award-info":[{"award-number":["PATHWAYS-200-059"]}],"id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Frontotemporal dementia (FTD) is a common form of dementia among early-onset cases. Several genetic factors for FTD have been revealed, but a large proportion of FTD cases still have an unidentified genetic origin. Recent studies highlighted common pathobiological mechanisms among neurodegenerative diseases. In the present study, we investigated a panel of candidate genes, previously described to be associated with FTD and\/or other neurodegenerative diseases by targeted next generation sequencing (NGS). We focused our study on sporadic FTD (sFTD), devoid of disease-causing mutations in GRN, MAPT and C9orf72. Since genetic factors have a substantially higher pathogenetic contribution in early onset patients than in late onset dementia, we selected patients with early onset (&lt;65 years). Our study revealed that, in 50% of patients, rare missense potentially pathogenetic variants in genes previously associated with Alzheimer\u2019s disease, Parkinson disease, amyotrophic lateral sclerosis and Lewy body dementia (GBA, ABCA7, PARK7, FUS, SORL1, LRRK2, ALS2), confirming genetic pleiotropy in neurodegeneration. In parallel, a synergic genetic effect on FTD is suggested by the presence of variants in five different genes in one single patient. Further studies employing genome-wide approaches might highlight pathogenic variants in novel genes that explain the still missing heritability of FTD.<\/jats:p>","DOI":"10.3390\/ijms20163903","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T06:38:02Z","timestamp":1565591882000},"page":"3903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Missing Heritability of Sporadic Frontotemporal Dementia: New Insights from Rare Variants in Neurodegenerative Candidate Genes"],"prefix":"10.3390","volume":"20","author":[{"given":"Miriam","family":"Ciani","sequence":"first","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Bonvicini","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Scassellati","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Carrara","sequence":"additional","affiliation":[{"name":"Service of Statistics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Maj","sequence":"additional","affiliation":[{"name":"Institute of Genomic Statistics and Bioinformatics, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Fostinelli","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliano","family":"Binetti","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Ghidoni","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-8141","authenticated-orcid":false,"given":"Luisa","family":"Benussi","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1212\/WNL.58.11.1615","article-title":"The prevalence of frontotemporal dementia","volume":"58","author":"Ratnavalli","year":"2002","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1159\/000077151","article-title":"Epidemiology of frontotemporal lobar degeneration","volume":"17","author":"Ikeda","year":"2004","journal-title":"Dement. 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