{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:34:15Z","timestamp":1791815655871,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative disorders, including behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non\u2010fluent variant PPA (nfvPPA). While a strong genetic component is implicated in FTD, genetic FTD in Asia is less frequently reported. We aimed to investigate the frequency of Southeast Asian FTD patients harbouring known genetic FTD variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 60 FTD\u2010spectrum patients (25 familial and 35 sporadic) from Singapore and the Philippines were included. All underwent next\u2010generation sequencing and repeat\u2010primed PCR for <jats:italic>C9orf72<\/jats:italic> expansion testing. Neurofilament light chain (NfL) levels were measured in a subset of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 26.6% (16\/60 cases) carried pathogenic or likely pathogenic variants in a FTD\u2010related gene, including: <jats:italic>MAPT<\/jats:italic> Gln351Arg (<jats:italic>n<\/jats:italic>\u00a0=\u20091); <jats:italic>GRN<\/jats:italic> Cys92Ter (<jats:italic>n<\/jats:italic>\u00a0=\u20091), Ser301Ter (<jats:italic>n<\/jats:italic>\u00a0=\u20092), c.462\u2009+\u20091G\u2009&gt;\u2009C (<jats:italic>n<\/jats:italic>\u00a0=\u20091); <jats:italic>C9orf72<\/jats:italic> expansion (35\u201370 repeats; <jats:italic>n<\/jats:italic>\u00a0=\u20098); <jats:italic>TREM2<\/jats:italic> Arg47Cys (<jats:italic>n<\/jats:italic>\u00a0=\u20091); and <jats:italic>OPTN<\/jats:italic> frameshift insertion (<jats:italic>n<\/jats:italic>\u00a0=\u20092). Genetic mutations accounted for 48% (12\/25) of patients with familial FTD, and 11.4% (4\/35) of patients with sporadic FTD. <jats:italic>C9orf72<\/jats:italic> repeat expansions were the most common genetic mutation (13.3%, 8\/60), followed by <jats:italic>GRN<\/jats:italic> (6.7%, 4\/60) variants. Within mutation carriers, plasma NfL was highest in a <jats:italic>C9orf72<\/jats:italic> expansion carrier, and CSF NfL was highest in a <jats:italic>GRN<\/jats:italic> splice variant carrier.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>In our cohort, genetic mutations are present in one\u2010quarter of FTD\u2010spectrum cases, and up to half of those with family history. Our findings highlight the importance of wider implementation of genetic testing in FTD patients from Southeast Asia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51744","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T11:53:27Z","timestamp":1676634807000},"page":"568-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>C9orf72<\/i> expansions are the most common cause of genetic frontotemporal dementia in a Southeast Asian cohort"],"prefix":"10.1002","volume":"10","author":[{"given":"Yi Jayne","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Neurology National Neuroscience Institute, Tan Tock Seng Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa C. 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