{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:21:04Z","timestamp":1779916864107,"version":"3.53.1"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in <jats:italic>PRKN<\/jats:italic> are the most common cause of autosomal recessive juvenile parkinsonism. The objective of this study was to investigate the association between genotype and pathology in patients with <jats:italic>PRKN<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a sequence and copy number variation analysis of <jats:italic>PRKN<\/jats:italic>, mRNA transcripts, Parkin protein expression, and neuropathology in 8 autopsied patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All the patients harbored biallelic <jats:italic>PRKN<\/jats:italic> mutations. Two patients were homozygous and heterozygous, respectively, for the missense mutation p.C431F. Seven patients had exon rearrangements, including 2 patients from a single family who harbored a homozygous deletion of exon 4, and 3 patients who carried a homozygous duplication of exons 6\u20137, a homozygous duplication of exons 10\u201311, and a heterozygous duplication of exons 2\u20134. In the other 2 patients, we found a compound heterozygous duplication of exon 2, deletion of exon 3, and a heterozygous duplication of exon 2. However, sequencing of cDNA prepared from mRNA revealed 2 different transcripts derived from triplication of exon 2 and deletion of exons 2\u20133 and from duplication of exons 2\u20134 and deletion of exons 3\u20134. Western blotting and immunohistochemistry revealed faint or no expression of Parkin in their brains. In the substantia nigra pars compacta, a subfield\u2010specific pattern of neuronal loss and mild gliosis were evident. Lewy bodies were found in 3 patients. Peripheral sensory neuronopathy was a feature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Genomic and mRNA analysis is needed to identify the <jats:italic>PRKN<\/jats:italic> mutations. Variable mutations may result in no or little production of mature Parkin and the histopathologic features may be similar.  \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28521","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T22:00:57Z","timestamp":1613253657000},"page":"1634-1643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genetic Variations and Neuropathologic Features of Patients with <i>PRKN<\/i> Mutations"],"prefix":"10.1002","volume":"36","author":[{"given":"Naohiko","family":"Seike","sequence":"first","affiliation":[{"name":"Department of Pathology Brain Research Institute, Niigata University  Niigata Japan"},{"name":"Division of Neurology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Yokoseki","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuhiko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Neurology NHO Niigata National Hospital  Kashiwazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Aida","sequence":"additional","affiliation":[{"name":"Department of Neurology NHO Niigata National Hospital  Kashiwazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Neurology NHO Niigata National Hospital  Kashiwazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-8156","authenticated-orcid":false,"given":"Masato","family":"Kanazawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Department of Neurology Ojiya Sakura Hospital  Ojiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Toyoshima","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Neurology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsushi","family":"Toda","sequence":"additional","affiliation":[{"name":"Department of Neurology Graduate School of Medicine, The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Onodera","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Disease Center Agano Hospital  Agano Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Kakita","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute, Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.1.160"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg142"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/33416"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13593"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1649"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10613"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv277"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181af7a33"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f4d832"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27193"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870100413"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.3_Part_1.437"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200008)48:2<245::AID-ANA15>3.0.CO;2-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8257(200009)15:5<884::AID-MDS1019>3.0.CO;2-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.05.005"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4244-07.2007"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306889200"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70238-8"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13249"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.01.005"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.172"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1132"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(03)00016-6"},{"key":"e_1_2_8_27_1","first-page":"6838965","article-title":"A case of Parkinson's disease with no Lewy body pathology due to a homozygous exon deletion in Parkin","author":"Johansen KK","year":"2018","journal-title":"Case Rep Neurol Med"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25346"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.3.890"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20587"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000134657.25904.0B"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.4.555"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(98)00015-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.06.010"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000230520.47768.1a"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.54.5.388"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.1096"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25220"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0991-7"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25792"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000204179.88955.fa"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181ac10a7"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.05.019"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000171859.85078.3d"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20113"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04407-4"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28521","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.28521","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28521","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:05:16Z","timestamp":1760965516000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.28521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,11]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/mds.28521"],"URL":"https:\/\/doi.org\/10.1002\/mds.28521","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,11]]},"assertion":[{"value":"2020-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}