{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:01:24Z","timestamp":1790460084259,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T00:00:00Z","timestamp":1511481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Mutations in <jats:italic><jats:styled-content style=\"fixed-case\">GLE1<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> export mediator<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">GLE1<\/jats:styled-content><\/jats:italic>) gene have previously been shown to cause motor neuron diseases such as lethal congenital contracture syndrome 1 (<jats:styled-content style=\"fixed-case\">LCCS1<\/jats:styled-content>) and lethal arthrogryposis with anterior horn cell disease (<jats:styled-content style=\"fixed-case\">LAAHD<\/jats:styled-content>), including arthrogryposis, fetal akinesis and motor neuron loss as common clinical features. The homozygous <jats:styled-content style=\"fixed-case\">Fin<jats:sub>Major<\/jats:sub><\/jats:styled-content> mutation p.T144_E145insPFQ has been described as one of the causes for <jats:styled-content style=\"fixed-case\">LCCS1<\/jats:styled-content> whereas <jats:styled-content style=\"fixed-case\">LAAHD<\/jats:styled-content> is caused by a heterocompound <jats:styled-content style=\"fixed-case\">Fin<jats:sub>Major<\/jats:sub><\/jats:styled-content> mutation together with p.<jats:styled-content style=\"fixed-case\">R569H<\/jats:styled-content>, p.<jats:styled-content style=\"fixed-case\">V617M<\/jats:styled-content> or p.<jats:styled-content style=\"fixed-case\">I684T<\/jats:styled-content> missense mutation. None of these heterocompound missense mutations have previously been reported as homozygous states. Here we present the clinical features of 2 siblings with a homozygous p.<jats:styled-content style=\"fixed-case\">I684T<\/jats:styled-content> mutation in <jats:italic><jats:styled-content style=\"fixed-case\">GLE1<\/jats:styled-content><\/jats:italic>. The patients suffered from similar, but milder symptoms than in <jats:styled-content style=\"fixed-case\">LCCS1<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LAAHD<\/jats:styled-content>, surviving up to 6\u2009months before they died due to a progressive disease course including respiratory failure. Arthrogryposis, lack of spontaneous movements, and epilepsy were notable in both cases and lack of anterior horn cells was identified in autopsy samples. Our studies on patient\u2010derived fibroblasts show that the homozygous p.<jats:styled-content style=\"fixed-case\">I684T<\/jats:styled-content> impairs the nuclear localization of <jats:styled-content style=\"fixed-case\">GLE1<\/jats:styled-content> further confirming the pathogenic role of this mutation.<\/jats:p>","DOI":"10.1111\/cge.13086","type":"journal-article","created":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T10:48:37Z","timestamp":1498646917000},"page":"173-177","source":"Crossref","is-referenced-by-count":8,"title":["A homozygous <scp>I684T<\/scp> in <scp>GLE1<\/scp> as a novel cause of arthrogryposis and motor neuron loss"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-5822","authenticated-orcid":false,"given":"T.","family":"Paakkola","sequence":"first","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Medical Research Center University of Oulu, Oulu University Hospital  Oulu Finland"},{"name":"Biocenter Oulu University of Oulu  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Vuopala","sequence":"additional","affiliation":[{"name":"Department of Pathology Lapland Central Hospital  Rovaniemi Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kokkonen","sequence":"additional","affiliation":[{"name":"Northern Finland Laboratory Centre Nordlab and Medical Research Centre Oulu University Hospital and University of Oulu  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ignatius","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Valkama","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Medical Research Center University of Oulu, Oulu University Hospital  Oulu Finland"},{"name":"Department of Children and Adolescents, Division of Pediatric Neurology Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-3205","authenticated-orcid":false,"given":"J.S.","family":"Moilanen","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Medical Research Center University of Oulu, Oulu University Hospital  Oulu Finland"},{"name":"Department of Clinical Genetics Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Fahiminiya","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Majewski","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Hinttala","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Medical Research Center University of Oulu, Oulu University Hospital  Oulu Finland"},{"name":"Biocenter Oulu University of Oulu  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Uusimaa","sequence":"additional","affiliation":[{"name":"PEDEGO Research Unit University of Oulu  Oulu Finland"},{"name":"Medical Research Center University of Oulu, Oulu University Hospital  Oulu Finland"},{"name":"Biocenter Oulu University of Oulu  Oulu Finland"},{"name":"Department of Children and Adolescents, Division of Pediatric Neurology Oulu University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.65"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/301968"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320290109"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(95)90109-4"},{"issue":"06","key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1055\/s-2008-1073045","article-title":"Lethal arthrogryposis in Finland\u2010a clinico\u2010pathological study of 83 cases during thirteen years","volume":"25","author":"Vuopala K","year":"1994","journal-title":"Neuropediatrics"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2541"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-3-294"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_6_10_1","unstructured":"Sequencing Initiative Suomi project (SISu). 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