{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:19:18Z","timestamp":1787660358512,"version":"build-2736575974"},"reference-count":10,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":236,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Case Reports in Neurological Medicine"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Parkinsonism\u2013dystonia Type 2 (PKDYS2) is a rare autosomal recessive disorder caused by\n                    <jats:italic>SLC18A2<\/jats:italic>\n                    variants affecting the vesicular monoamine transporter 2 (VMAT2). We report the first genetically confirmed Iranian patient, an 18\u2010month\u2010old boy presenting with profound developmental delay, axial hypotonia, limb hypertonia, dystonia, oculogyric crises, ptosis, and autonomic dysfunction. Brain MRI, metabolic studies, and neurophysiological evaluations were normal. Whole\u2010exome sequencing identified a novel homozygous canonical splice\u2010site variant in\n                    <jats:italic>SLC18A2<\/jats:italic>\n                    (NM_003054.6:c.1071\u20102A\u2009&gt;\u2009G), confirmed by Sanger sequencing and absent from population databases. SpliceAI predicted loss of the native splice acceptor site (DS_AL\u2009=\u20090.74), supporting a deleterious effect on RNA splicing. According to ACMG criteria, the variant was classified as likely pathogenic. Levodopa\u2013benserazide failed to provide sustained benefit and caused irritability and insomnia, whereas pramipexole produced modest improvement in bradykinesia, ptosis, and sweating with persistence of dystonia and oculogyric crises. Comparison with reported international cases shows a consistent phenotype and limited therapeutic response. This case expands the mutational spectrum of\n                    <jats:italic>SLC18A2<\/jats:italic>\n                    \u2010related disease and highlights the importance of early genetic diagnosis.\n                  <\/jats:p>","DOI":"10.1155\/crnm\/2230320","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:50Z","timestamp":1787657270000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Novel\n                    <i>SLC18A2<\/i>\n                    Splicing Variant in a Case of Infantile Parkinsonism\u2013Dystonia Type 2"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2192-693X","authenticated-orcid":false,"given":"Ali","family":"Nikkhah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7477-4688","authenticated-orcid":false,"given":"Reza Shervin","family":"Badv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-4779","authenticated-orcid":false,"given":"Seyed Amir Hasan","family":"Habibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-5365","authenticated-orcid":false,"given":"Giovanna","family":"Zorzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2977-3421","authenticated-orcid":false,"given":"Maryam","family":"Mehdizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.09.010"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.52020"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/4767647"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1207281"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9897-6"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12030"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2021.1938036"},{"key":"e_1_2_11_8_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.parkreldis.2025.107930","article-title":"SLC18A2 Associated infantile-onset-parkinsonism-dystonia 2: a Novel Genotype","author":"Janardhanan A.","year":"2025","journal-title":"Parkinsonism & Related Disorders"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(11)70141-7"},{"key":"e_1_2_11_10_2","first-page":"1115","volume-title":"VMAT2 and Parkinson\u2019s Disease: Harnessing the Dopamine Vesicle","author":"Lohr K. M.","year":"2014"}],"container-title":["Case Reports in Neurological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/crnm\/2230320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/crnm\/2230320","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/crnm\/2230320","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:51Z","timestamp":1787657271000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/crnm\/2230320"}},"subtitle":[],"editor":[{"given":"Semonti","family":"Nandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/crnm\/2230320"],"URL":"https:\/\/doi.org\/10.1155\/crnm\/2230320","archive":["Portico"],"relation":{},"ISSN":["2090-6668","2090-6676"],"issn-type":[{"value":"2090-6668","type":"print"},{"value":"2090-6676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2230320"}}