{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:05Z","timestamp":1753861745171,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary spastic paraplegia (HSP) is a group of familial diseases characterized by progressive corticospinal tract degeneration. Clinically, patients present with lower\u2010limb spasticity and weakness. To date, more than 80 genetic HSP types have been identified. Despite advances in molecular genetics, novel HSP gene discoveries are ongoing, with a low genetic diagnostic yield. In this study, we aimed to determine pathogenic variants in a family with HSP, which was not diagnosed through conventional genetic testing. We clinically characterized a large family and conducted whole genome sequencing (WGS) analysis of four affected and three unaffected individuals in the family to identify the genetic cause of HSP. This family had autosomal dominant pure (uncomplicated) late childhood\u2010onset HSP. The patients' symptoms accelerated between the ages of 20 and 30. Brain magnetic resonance images typically showed white matter changes, a thin corpus callosum, and cerebellar atrophy. We identified a heterozygous missense variant, <jats:italic>KCNJ3<\/jats:italic> c.1297T&gt;G (p.Leu433Val), through WGS and family genetic analysis, confirmed by Sanger sequencing. We suggest that the identification of <jats:italic>KCNJ3<\/jats:italic> c.1297T&gt;G (p.Leu433Val) constitutes the discovery of a potential novel gene responsible for HSP in this family. This is the first study to report the possible role of a <jats:italic>KCNJ3<\/jats:italic> variant in HSP pathogenesis. Our findings further expand the phenotypic and genotypic spectrum of HSP.<\/jats:p>","DOI":"10.1002\/ajmg.b.32984","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T11:28:50Z","timestamp":1712748530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp><i>KCNJ3<\/i><\/scp> is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia identified using whole genome sequencing"],"prefix":"10.1002","volume":"195","author":[{"given":"Woong\u2010Woo","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology, Nowon Eulji Medical Center Eulji University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7294-229X","authenticated-orcid":false,"given":"Cha Gon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nowon Eulji Medical Center Eulji University School of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Seok","family":"Ki","sequence":"additional","affiliation":[{"name":"GC Genome  Yongin Gyeonggi\u2010do Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_2_1","DOI":"10.1093\/nar\/gku1205"},{"doi-asserted-by":"publisher","key":"e_1_2_9_3_1","DOI":"10.1016\/s0143-4160(03)00141-6"},{"doi-asserted-by":"publisher","key":"e_1_2_9_4_1","DOI":"10.3389\/fneur.2018.00958"},{"doi-asserted-by":"publisher","key":"e_1_2_9_5_1","DOI":"10.1371\/journal.pcbi.1010959"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1016\/j.ebiom.2022.104115"},{"doi-asserted-by":"publisher","key":"e_1_2_9_7_1","DOI":"10.1097\/md.0000000000020193"},{"doi-asserted-by":"publisher","key":"e_1_2_9_8_1","DOI":"10.1016\/bs.irn.2015.06.001"},{"doi-asserted-by":"publisher","key":"e_1_2_9_9_1","DOI":"10.1007\/s12311-016-0803-z"},{"doi-asserted-by":"publisher","key":"e_1_2_9_10_1","DOI":"10.1152\/ajpcell.00457.2022"},{"doi-asserted-by":"publisher","key":"e_1_2_9_11_1","DOI":"10.1093\/brain\/awp056"},{"doi-asserted-by":"publisher","key":"e_1_2_9_12_1","DOI":"10.1590\/0004-282x20170160"},{"doi-asserted-by":"publisher","key":"e_1_2_9_13_1","DOI":"10.1086\/302776"},{"doi-asserted-by":"publisher","key":"e_1_2_9_14_1","DOI":"10.1111\/j.1439-0388.2007.00673.x"},{"doi-asserted-by":"publisher","key":"e_1_2_9_15_1","DOI":"10.1002\/mds.22363"},{"doi-asserted-by":"publisher","key":"e_1_2_9_16_1","DOI":"10.1086\/339935"},{"doi-asserted-by":"publisher","key":"e_1_2_9_17_1","DOI":"10.1016\/s0140-6736(83)92879-9"},{"volume-title":"GeneReviews(\u00ae) (updated 2021 Feb 11 ed)","year":"1993","author":"Hedera P.","key":"e_1_2_9_18_1"},{"doi-asserted-by":"publisher","key":"e_1_2_9_19_1","DOI":"10.1016\/j.ajhg.2016.04.003"},{"doi-asserted-by":"publisher","key":"e_1_2_9_20_1","DOI":"10.1038\/ng0794-402"},{"doi-asserted-by":"publisher","key":"e_1_2_9_21_1","DOI":"10.1093\/brain\/aww111"},{"doi-asserted-by":"publisher","key":"e_1_2_9_22_1","DOI":"10.1093\/nar\/gkaa1043"},{"doi-asserted-by":"publisher","key":"e_1_2_9_23_1","DOI":"10.1523\/jneurosci.3484-05.2005"},{"doi-asserted-by":"publisher","key":"e_1_2_9_24_1","DOI":"10.1136\/jmg-2023-109201"},{"doi-asserted-by":"publisher","key":"e_1_2_9_25_1","DOI":"10.1007\/s00109-018-1655-4"},{"doi-asserted-by":"publisher","key":"e_1_2_9_26_1","DOI":"10.1016\/bs.irn.2015.05.009"},{"doi-asserted-by":"publisher","key":"e_1_2_9_27_1","DOI":"10.1152\/ajpcell.00102.2022"},{"doi-asserted-by":"publisher","key":"e_1_2_9_28_1","DOI":"10.3390\/brainsci11030403"},{"doi-asserted-by":"publisher","key":"e_1_2_9_29_1","DOI":"10.1046\/j.1432-1327.2000.01670.x"},{"doi-asserted-by":"publisher","key":"e_1_2_9_30_1","DOI":"10.1038\/ejhg.2015.226"},{"doi-asserted-by":"publisher","key":"e_1_2_9_31_1","DOI":"10.1007\/s00439-015-1631-9"},{"doi-asserted-by":"publisher","key":"e_1_2_9_32_1","DOI":"10.1016\/j.ajhg.2022.10.013"},{"doi-asserted-by":"publisher","key":"e_1_2_9_33_1","DOI":"10.1038\/gim.2015.30"},{"doi-asserted-by":"publisher","key":"e_1_2_9_34_1","DOI":"10.1093\/database\/baq020"},{"doi-asserted-by":"publisher","key":"e_1_2_9_35_1","DOI":"10.1002\/ana.24611"},{"volume-title":"Amyotrophic lateral sclerosis overview","year":"1993","author":"Siddique N.","key":"e_1_2_9_36_1"},{"doi-asserted-by":"publisher","key":"e_1_2_9_37_1","DOI":"10.1038\/s41431-022-01113-x"},{"doi-asserted-by":"publisher","key":"e_1_2_9_38_1","DOI":"10.1007\/s10048-018-0545-9"},{"doi-asserted-by":"publisher","key":"e_1_2_9_39_1","DOI":"10.1126\/science.1260419"},{"doi-asserted-by":"publisher","key":"e_1_2_9_40_1","DOI":"10.1073\/pnas.1212019110"},{"doi-asserted-by":"publisher","key":"e_1_2_9_41_1","DOI":"10.1016\/j.celrep.2020.107770"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.32984","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T12:22:37Z","timestamp":1731586957000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.32984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,10]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/ajmg.b.32984"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.32984","archive":["Portico"],"relation":{},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"type":"print","value":"1552-4841"},{"type":"electronic","value":"1552-485X"}],"subject":[],"published":{"date-parts":[[2024,4,10]]},"assertion":[{"value":"2024-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e32984"}}