{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:37:20Z","timestamp":1778618240450,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Mutations in the <jats:styled-content style=\"fixed-case\"><jats:italic>SCARB2<\/jats:italic><\/jats:styled-content> gene cause a rare autosomal recessive disease, progressive myoclonus epilepsy (<jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content>) with or without renal failure, the former also being designated action myoclonus\u2010renal failure syndrome. Although reported cases have been accumulating, only a few have described its neuropathology. We studied two <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>apanese patients with <jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content> without renal failure, in whom the ages at onset and disease durations were 45 and 20 years, and 14 and 8.5 years respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sequencing and restriction analysis of the <jats:styled-content style=\"fixed-case\"><jats:italic>SCARB2<\/jats:italic><\/jats:styled-content> gene and neuropathological examination with immunohistochemistry were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene analyses revealed novel homozygous frameshift and nonsense mutations in the <jats:styled-content style=\"fixed-case\"><jats:italic>SCARB2<\/jats:italic><\/jats:styled-content> gene. Both cases exhibited deposition of brown pigment in the brain, especially the cerebellar and cerebral cortices. Ultrastructurally, the pigment granules were localized in astrocytes. Neuronal loss and gliosis were also evident in the brain, including the pallidoluysian and cerebello\u2010olivary systems. The spinal cord was also affected. Such changes were less severe in one patient with late\u2010onset disease than in the other patient with early\u2010onset disease. In brain and kidney sections, immunostaining with an antibody against the <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010terminus of human <jats:styled-content style=\"fixed-case\">SCARB<\/jats:styled-content>2 revealed decreased levels and no expression of the protein respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The frameshift mutation detected in the patient with late\u2010onset disease is a hitherto undescribed, unique type of <jats:styled-content style=\"fixed-case\"><jats:italic>SCARB2<\/jats:italic><\/jats:styled-content> gene mutation. The present two patients are the first reported to have clearly demonstrated both extraneuronal brown pigment deposition and system neurodegeneration as neuropathological features of <jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content> with <jats:styled-content style=\"fixed-case\"><jats:italic>SCARB2<\/jats:italic><\/jats:styled-content> mutations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12057","type":"journal-article","created":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T10:47:46Z","timestamp":1368182866000},"page":"551-563","source":"Crossref","is-referenced-by-count":15,"title":["Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of <scp>J<\/scp>apanese patients with novel <scp><i>SCARB2<\/i><\/scp> mutations"],"prefix":"10.1111","volume":"40","author":[{"given":"Yong\u2010Juan","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Pathology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izumi","family":"Aida","sequence":"additional","affiliation":[{"name":"Department of Neurology Niigata National Hospital  Kashiwazaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuko","family":"Toyoshima","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Division of Pathology Niigata Neurosurgical Hospital  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Neurology Niigata National Hospital  Kashiwazaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruhiko","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Matsuhama Hospital  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoyo","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Onodera","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiyoshi","family":"Kakita","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute University of Niigata  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,7]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"87","article-title":"Action myoclonus\u2010renal failure syndrome: a previously unrecognized neurological disorder unmasked by advances in nephrology","volume":"43","author":"Andermann E","year":"1986","journal-title":"Adv Neurol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh263"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn124"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.019"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21765"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2011.06.018"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03307.x"},{"key":"e_1_2_8_9_1","first-page":"142","article-title":"Myoclonus epilepsy with brown pigment and cerebellar cortical degeneration (in Japanese with English abstract)","volume":"31","author":"Takeda S","year":"1987","journal-title":"Shinkei Kenkyo No Shinpo"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00543869"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000084558"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.32.8.798"},{"key":"e_1_2_8_13_1","first-page":"619","volume-title":"Ultrastructural Pathology of the Cell and Matrix","author":"Ghadially FN","year":"1997"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781444341256.ch29"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/31.1.125"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000238424.23177.5e"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.120"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-11-134"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25083"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1017\/S0317167100120438","article-title":"Pigment variant of neuronal ceroid\u2010lipofuscinosis (Kufs' disease)","volume":"4","author":"Horoupian D","year":"1977","journal-title":"Can J Neurol Sci"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02117.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5641-1"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12057","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T06:25:48Z","timestamp":1696227948000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1111\/nan.12057"],"URL":"https:\/\/doi.org\/10.1111\/nan.12057","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7]]}}}