{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:44:04Z","timestamp":1790001844808,"version":"4.0.1"},"reference-count":96,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["5XMille\u20142018"],"award-info":[{"award-number":["5XMille\u20142018"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Dementing disorders are a complex group of neurodegenerative diseases characterised by different, but often overlapping, pathological pathways. Genetics have been largely associated with the development or the risk to develop dementing diseases. Recent advances in molecular technologies permit analyzing of several genes in a small time, but the interpretation analysis is complicated by several factors: the clinical complexity of neurodegenerative disorders, the frequency of co-morbidities, and the high phenotypic heterogeneity of genetic diseases. Genetic counselling supports the diagnostic path, providing an accurate familial and phenotypic characterisation of patients. In this review, we summarise neurodegenerative dementing disorders and their genetic determinants. Genetic variants and associated phenotypes will be divided into high and low impact, in order to reflect the pathologic continuum between multifactorial and mendelian genetic factors. Moreover, we report a molecular characterisation of genes associated with neurodegenerative disorders with cognitive impairment. In particular, the high frequency of rare coding genetic variants in dementing genes strongly supports the role of geneticists in both, clinical phenotype characterisation and interpretation of genotypic data. The smart application of exome analysis to dementia patients, with a pre-analytical selection on familial, clinical, and instrumental features, improves the diagnostic yield of genetic test, reduces time for diagnosis, and allows a rapid and personalised management of disease.<\/jats:p>","DOI":"10.3390\/jpm11060474","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T10:30:32Z","timestamp":1622025032000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic Counselling Improves the Molecular Characterisation of Dementing Disorders"],"prefix":"10.3390","volume":"11","author":[{"given":"Stefania","family":"Zampatti","sequence":"first","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Ragazzo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Peconi","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Luciano","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gambardella","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3503-3318","authenticated-orcid":false,"given":"Valerio","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-0920","authenticated-orcid":false,"given":"Claudia","family":"Strafella","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Cascella","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Department of Biomedical Sciences, Catholic University Our Lady of Good Counsel, 1000 Tirana, Albania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Caltagirone","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Giardina","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/alz.12068","article-title":"2020 Alzheimer\u2019s disease facts and figures","volume":"16","author":"Zhao","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","article-title":"The global prevalence of dementia: A systematic review and metaanalysis","volume":"9","author":"Prince","year":"2013","journal-title":"Alzheimers Dement."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e519","DOI":"10.1212\/WNL.0000000000010022","article-title":"Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium","volume":"95","author":"Wolters","year":"2020","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3233\/JAD-191092","article-title":"The Prevalence of Dementia: A Systematic Review and Meta-Analysis","volume":"73","author":"Cao","year":"2020","journal-title":"J. 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