{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:05:02Z","timestamp":1747184702294,"version":"3.40.5"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["StG\u20102016_714388_NeuroTRACK"],"award-info":[{"award-number":["StG\u20102016_714388_NeuroTRACK"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Q336H is a rare <jats:italic>MAPT<\/jats:italic> mutation, previously found in a single patient with behavioral variant frontotemporal dementia and tau pathology (Pick bodies). Here, we describe the clinical characteristics of two members of a new family carrying the Q336H <jats:italic>MAPT<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical, genetic, and neuroradiological assessment and follow\u2010up of the proband were made.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At age 37 years, the proband developed naming and object recognition impairment, due to a lack of knowledge. After 3\u00a0years, he developed behavioral disorders. Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography showed the involvement of the left temporal pole. A diagnosis of semantic variant primary progressive aphasia (svPPA) was made. At follow\u2010up after 6 and 12\u00a0months, a rapid worsening of cognitive deficits occurred. His parent presented, at age 65 years, slowly progressive memory deficits without behavioral impairment, and, on MRI, evidence of mesial temporal atrophy, consistent with a clinical diagnosis of Alzheimer disease (AD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the second family carrying the <jats:italic>MAPT<\/jats:italic> Q336H mutation reported so far. We showed that svPPA and AD\u2010like phenotype can be associated with this mutation. A wide clinical variability exists at the intrafamilial level for Q336H <jats:italic>MAPT<\/jats:italic> mutation, pointing to genetic and\/or environmental influencing factors on disease expression. We also confirmed that svPPA can be associated with <jats:italic>MAPT<\/jats:italic> mutations, suggesting that this gene should be analyzed also in patients with svPPA, especially with early onset. In addition, an AD\u2010like phenotype may be associated with this mutation, suggesting its different effects on protein misfolding and aggregation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15250","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T15:14:41Z","timestamp":1642000481000},"page":"1529-1533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>MAPT<\/i> Q336H mutation: Intrafamilial phenotypic heterogeneity in a new Italian family"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-2886","authenticated-orcid":false,"given":"Cristina","family":"Villa","sequence":"first","affiliation":[{"name":"Neurology V and Neuropathology Unit IRCCS Foundation Carlo Besta Neurological Institute  Milan 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