{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:10:28Z","timestamp":1753891828297,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PNRR-M4C2-I1.3 Project PE_00000019 \u201cHEAL ITALIA\u201d to Paola Grammatico CUP B53C22004000006"],"award-info":[{"award-number":["PNRR-M4C2-I1.3 Project PE_00000019 \u201cHEAL ITALIA\u201d to Paola Grammatico CUP B53C22004000006"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Folliculin, encoded by <jats:italic>FLCN<\/jats:italic> gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt\u2013Hogg\u2013Dub\u00e9 (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patient and results<\/jats:title><jats:p>We report a 74-years-old woman diagnosed with dementia and carrying a <jats:italic>FLCN<\/jats:italic> alteration in absence of any sign of BHD. She also carried an alteration of <jats:italic>MAT1A<\/jats:italic> gene, which is also implicated in the regulation of mTORC1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The <jats:italic>MAT1A<\/jats:italic> variant could have prevented the development of a <jats:italic>FLCN<\/jats:italic>-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1304080","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T04:15:12Z","timestamp":1704428112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A pathogenic variant in the FLCN gene presenting with pure dementia: is autophagy at the intersection between neurodegeneration and cancer?"],"prefix":"10.3389","volume":"17","author":[{"given":"Irene","family":"Bottillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Laino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Azzar\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Lintas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Cassano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Di Lazzaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ursini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Motolese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Bargiacchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Formicola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorella","family":"Gurrieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/tra.12477","article-title":"C9orf72: At the intersection of lysosome cell biology and neurodegenerative disease.","volume":"18","author":"Amick","year":"2017","journal-title":"Traffic"},{"key":"B2","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1091\/mbc.e16-01-0003","article-title":"C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling.","volume":"27","author":"Amick","year":"2016","journal-title":"Mol. 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