{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:01:50Z","timestamp":1773327710088,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T00:00:00Z","timestamp":1522713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H01331"],"award-info":[{"award-number":["16H01331"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["16824947"],"award-info":[{"award-number":["16824947"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["16815631"],"award-info":[{"award-number":["16815631"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 NS072187"],"award-info":[{"award-number":["P50 NS072187"]}],"id":[{"id":"10.13039\/100000002","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":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Mutations in colony\u2010stimulating factor 1 receptor (<jats:italic><jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R<\/jats:italic>) cause adult\u2010onset leukoencephalopathy with axonal spheroids and pigmented glia (<jats:styled-content style=\"fixed-case\">ALSP<\/jats:styled-content>). Patients with <jats:styled-content style=\"fixed-case\">ALSP<\/jats:styled-content> can be misdiagnosed as having acute ischemic stroke due to hyperintensity lesions on diffusion\u2010weighted magnetic resonance imaging. Mutant <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R proteins identified in <jats:styled-content style=\"fixed-case\">ALSP<\/jats:styled-content> show a complete loss of autophosphorylation of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted mutation screening of <jats:italic><jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R<\/jats:italic> in 123 patients with definite acute ischemic cerebrovascular syndrome and positive family history of stroke. The pathogenicity of identified variants was evaluated using functional analyses. The levels of autophosphorylation of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R in response to treatment with ligands of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R were examined in cells transfected with wild\u2010type and mutant <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified eight <jats:italic><jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R<\/jats:italic> variants, six were known non\u2010pathogenic polymorphisms, whereas the other two were missense variants inducing substitution of amino acid residues (p.Glu573Lys and p.Gly747Arg). Functional assay showed that the levels of autophosphorylation of p.Gly747Arg were similar to those of wild\u2010type when treated with ligands. The autophosphorylation of p.Glu573Lys was detectable, but significantly decreased compared with those of wild\u2010type <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R (<jats:italic>P<\/jats:italic> &lt; 0.001, two\u2010way <jats:sc>anova<\/jats:sc> with Bonferroni). The clinical presentation of the patient with p.Glu573Lys was consistent with cerebral embolism. The patient did not have typical clinical findings of <jats:styled-content style=\"fixed-case\">ALSP<\/jats:styled-content>. However, periventricular white matter abnormalities, unrelated to the recent infarct, were evident on brain magnetic resonance imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In contrast to <jats:styled-content style=\"fixed-case\">ALSP<\/jats:styled-content>\u2010associated missense mutations, <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R p.Glu573Lys variant in a patient with acute ischemic cerebrovascular syndrome showed a partial loss of autophosphorylation of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R; its clinical significance warrants further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13611","type":"journal-article","created":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T15:32:43Z","timestamp":1520350363000},"page":"875-881","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Partial loss of function of colony\u2010stimulating factor 1 receptor in a patient with white matter abnormalities"],"prefix":"10.1111","volume":"25","author":[{"given":"T.","family":"Konno","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville FL USA"},{"name":"Department of Neurology Brain Research Institute Niigata University Niigata"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute Niigata University Niigata"},{"name":"Department of Molecular Genetics Brain Research Institute Niigata University Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"Harriott","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Mezaki","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute Niigata University Niigata"},{"name":"Department of Molecular Genetics Brain Research Institute Niigata University Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. S.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Rademakers","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Jacksonville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O. 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