{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:09:46Z","timestamp":1790244586918,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To assess the phenotype and genotype of 10 new patients with biallelic\n                      <jats:italic>RCC1<\/jats:italic>\n                      variants who presented with axonal neuropathy, and assess functional consequences in\u00a0vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      In this retrospective, multicentre, observational study, we identified 10 individuals from six families with biallelic\n                      <jats:italic>RCC1<\/jats:italic>\n                      missense variants who had previously developed axonal neuropathy (six males and females females; mean age 20.2\u2009months, SD 21.0\u2009months, range 58.0\u2009months). Survival analyses were performed using data from the current cohort and previously reported patients. The functional consequences of five new missense variants (p.Leu38Val, p.Ala98Val, p.Arg139His, p.Arg217Trp, p.Gly380Arg) were assessed using thermal stability, guanosine triphosphate exchange factor activity, and nucleocytoplasmic transport rescue assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Most patients presented in early childhood with infection\u2010triggered acute motor axonal neuropathy. We also identified patients with mild chronic neuropathy and early\u2010onset neurodevelopmental disease. Statistical analysis indicated that disease onset at or before 2\u2009years of age was associated with poorer survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.047). Functional studies revealed that new variants reduced protein thermal stability, guanosine triphosphate exchange factor activity, and Ran nucleocytoplasmic localization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RCC1<\/jats:italic>\n                      neuropathy presents a broader clinical spectrum than previously recognized, with ascertainment previously biased for children with severe rapid\u2010onset disease. Our findings support dysfunction of nucleocytoplasmic transport as a pathogenic mechanism in axonal neuropathy. Earlier age at onset was associated with poorer prognosis, which may guide management in future paediatric patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dmcn.70550","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:25:23Z","timestamp":1790241923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>RCC1<\/i>\n                    <\/scp>\n                    neuropathy mimics childhood axonal Guillain\u2013Barr\u00e9 syndrome with variable clinical severity and survival"],"prefix":"10.1111","author":[{"given":"Han","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Evolution, Infection and Genomics, FMBH University of Manchester  Manchester UK"},{"name":"Department of Genomic Medicine University of Manchester NHS Foundation Trust  Manchester UK"},{"name":"Paediatrics Department Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beril","family":"Din","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, FMBH University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, FMBH University of Manchester  Manchester UK"},{"name":"Department of Genomic Medicine University of Manchester NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"RCC1 Neuropathy Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T.","family":"O'Keefe","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, FMBH University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, FMBH University of Manchester  Manchester UK"},{"name":"Department of Genomic Medicine University of Manchester NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5951-2199","authenticated-orcid":false,"given":"J. Robert","family":"Harkness","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, FMBH University of Manchester  Manchester UK"},{"name":"Department of Genomic Medicine University of Manchester NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(25)00198\u2010X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(25)00240\u20106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102194"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.70156"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201008724\u2010w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102308\u20107"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460\u20102075.1991.tb08068.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100627"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010022\u201006033\u20108"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010019\u201001979\u2010w"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010014\u20108331\u20109"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00708\u201006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010021\u201000973\u20101"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2026.1765786"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010026\u201000912\u20104"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2026.2645262"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103616"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.70008"}],"container-title":["Developmental Medicine &amp; Child Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.70550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dmcn.70550","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.70550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:25:23Z","timestamp":1790241923000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dmcn.70550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":20,"alternative-id":["10.1111\/dmcn.70550"],"URL":"https:\/\/doi.org\/10.1111\/dmcn.70550","archive":["Portico"],"relation":{},"ISSN":["0012-1622","1469-8749"],"issn-type":[{"value":"0012-1622","type":"print"},{"value":"1469-8749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"assertion":[{"value":"2026-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"dmcn.70550"}}