{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:06:12Z","timestamp":1791295572795,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2002,11,4]],"date-time":"2002-11-04T00:00:00Z","timestamp":1036368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alexander's disease, a leukodystrophy characterized by Rosenthal fibers (RFs) in the brain, is categorized into three subtypes: infantile, juvenile, and adult. Although most are sporadic, occasional familial Alexander's disease cases have been reported for each subtype. Hereditary adult\u2010onset Alexander's disease shows progressive spastic paresis, bulbar or pseudobulbar palsy, palatal myoclonus symptomatologically, and prominent atrophy of the medulla oblongata and upper spinal cord on magnetic resonance imaging. Recent identification of <jats:italic>GFAP<\/jats:italic> gene mutations in the sporadic infantile\u2010 and juvenile\u2010onset Alexander's disease prompted us to examine the <jats:italic>GFAP<\/jats:italic> gene in two Japanese hereditary adult\u2010onset Alexander's disease brothers with autopsy in one case. Both had spastic paresis without palatal myoclonus, and magnetic resonance imaging showed marked atrophy of the medulla oblongata and cervicothoracic cord. The autopsy showed severely involved shrunken pyramids, but scarce Rosenthal fibers (RFs). Moderate numbers of Rosenthal fibers (RFs) were observed in the stratum subcallosum and hippocampal fimbria. In both cases, we found a novel missense mutation of a G\u2010to\u2010T transition at nucleotide 841 in the <jats:italic>GFAP<\/jats:italic> gene that results in the substitution of arginine for leucine at amino acid residue 276 (R276L). This is the first report of identification of the causative mutation of the <jats:italic>GFAP<\/jats:italic> gene for neuropathologically proven hereditary adult\u2010onset Alexander's disease, suggesting a common molecular mechanism underlies the three Alexander's disease subtypes.<\/jats:p>","DOI":"10.1002\/ana.10375","type":"journal-article","created":{"date-parts":[[2002,12,2]],"date-time":"2002-12-02T13:54:44Z","timestamp":1038837284000},"page":"779-785","source":"Crossref","is-referenced-by-count":99,"title":["Identification of <i>GFAP<\/i> gene mutation in hereditary adult\u2010onset Alexander's disease"],"prefix":"10.1002","volume":"52","author":[{"given":"Michito","family":"Namekawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Takiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Takayashiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumi","family":"Sakoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruo","family":"Shimazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Taguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasufumi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoyo","family":"Nishizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imaharu","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,11,4]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/72.3.373"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/108.2.367"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1059669"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00689163"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1968.00480050064006"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-197010000-00002"},{"key":"e_1_2_6_8_2","first-page":"23","article-title":"Alexander's 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