{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:58Z","timestamp":1753861798976,"version":"3.41.2"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministry of Education, University and Research","doi-asserted-by":"publisher","award":["2022B9WY4A"],"award-info":[{"award-number":["2022B9WY4A"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Adult\u2010onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), also termed hereditary diffuse leukoencephalopathy with spheroids\u20101 (HDLS1), results from mutations in the <jats:italic>CSF1R<\/jats:italic> gene and leads to progressive leukoencephalopathy. This autosomal dominant condition typically manifests in the fourth or fifth decade of life with a combination of early\u2010onset dementia, neuropsychiatric changes, and motor symptoms. <jats:italic>CSF1R<\/jats:italic> mutations are predominantly located within the tyrosine kinase domain (TKD) of the protein, crucial for its kinase activity. However, variants outside the TKD can also disrupt kinase function. Here, we report a 58\u2010year\u2010old man with early\u2010onset dementia and a novel missense variant [c.1735C&gt;G, p.(Arg579Gly)] just outside the TKD of <jats:italic>CSF1R<\/jats:italic>. Functional analysis showed impaired autophosphorylation of the mutant protein, supporting its pathogenicity. This case highlights the importance of functional validation in newly identified <jats:italic>CSF1R<\/jats:italic> variants, underscoring the need for comprehensive genetic and functional analysis in diagnosing and understanding this rare neurological disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.64065","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T08:21:02Z","timestamp":1743236462000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the Tyrosine Kinase Domain of <scp>CSF1R<\/scp>? A Case Report From an Adult\u2010Onset Leukoencephalopathy"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-3129","authenticated-orcid":false,"given":"Piervito","family":"Lopriore","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine Neurological Institute, University of Pisa  Pisa Italy"},{"name":"Scuola Superiore Sant'Anna, Ph.D. School in Translational Medicine  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianmichele","family":"Migaleddu","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Azienda Ospedaliero\u2010Universitaria Pisana  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Chien","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Life Sciences National Chung Hsing University  Taichung Taiwan"},{"name":"The iEGG and Animal Biotechnology Research Center National Chung Hsing University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Fogli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics University Hospital of Pisa  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Adelaide","family":"Caligo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics University Hospital of Pisa  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine Neurological Institute, University of Pisa  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirco","family":"Cosottini","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Department of Translational Research on New Technologies in Medicine and Surgery University of Pisa  Pisa 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