{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:19:01Z","timestamp":1780438741497,"version":"3.54.1"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,14]],"date-time":"2020-06-14T00:00:00Z","timestamp":1592092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","award":["19272"],"award-info":[{"award-number":["19272"]}],"id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["Grant FP7\/2007\u20132013 (NEUROMICS; Grant No. 2012)"],"award-info":[{"award-number":["Grant FP7\/2007\u20132013 (NEUROMICS; Grant No. 2012)"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201010\u2010INBS\u201009"],"award-info":[{"award-number":["ANR\u201010\u2010INBS\u201009"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>GLE1<\/jats:italic> (GLE1, RNA Export Mediator, OMIM#603371) variants are associated with severe autosomal recessive motor neuron diseases, that are lethal congenital contracture syndrome 1 (LCCS1, OMIM#253310) and congenital arthrogryposis with anterior horn cell disease (CAAHD, OMIM#611890).<\/jats:p><jats:p>The clinical spectrum of <jats:italic>GLE1<\/jats:italic>\u2010related disorders has been expanding these past years, including with adult\u2010onset amyotrophic lateral sclerosis (ALS) <jats:italic>GLE1<\/jats:italic>\u2010related forms, especially through the new molecular diagnosis strategies associated with the emergence of next\u2010generation sequencing (NGS) technologies. However, despite this phenotypic variability, reported congenital or ALS adult\u2010onset forms remain severe, leading to premature death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Through multidisciplinary interactions between our Neuropediatric and Medical Genetics departments, we were able to diagnose two siblings presenting with congenital disorder, using an NGS approach accordingly to the novel French national recommendations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two siblings with very similar clinical features, meaning neuromuscular disorder of neonatal onset with progressive improvement, were examined in our Neuropediatrics department. The clinical presentation evoked initially congenital myopathy with autosomal recessive inheritance. However, additional symptoms such as mild dysmorphic features including high anterior hairline, downslanted palpebral fissures, anteverted nares, smooth philtrum with thin upper\u2010lip, narrow mouth and microretrognathia or delayed expressive language and postnatal growth retardation were suggestive of a more complex clinical presentation and molecular diagnosis. Our NGS approach revealed an unexpected molecular diagnosis for these two siblings, meaning the presence of the homozygous c.1808G&gt;T <jats:italic>GLE1<\/jats:italic> variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We here report the mildest phenotype ever described, in two siblings carrying the homozygous c.1808G&gt;T <jats:italic>GLE1<\/jats:italic> variant, further widening the clinical spectrum of <jats:italic>GLE1<\/jats:italic>\u2010related diseases. Moreover, by reflecting current medical practice, this case report confirms the importance of establishing regular multidisciplinary meetings, essential for discussing such difficult clinical presentations to finally enable molecular diagnosis, especially when NGS technologies are used.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1277","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T01:48:38Z","timestamp":1592185718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Extension of the phenotypic spectrum of <i>GLE1<\/i>\u2010related disorders to a mild congenital form resembling congenital myopathy"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4992-5157","authenticated-orcid":false,"given":"Mathieu","family":"Cerino","sequence":"first","affiliation":[{"name":"Aix Marseille Univ Inserm, U1251\u2010MMG, Marseille Medical Genetics Marseille France"},{"name":"APHM, H\u00f4pital Timone Enfants D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale Marseille France"},{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"},{"name":"APHM, H\u00f4pital de la Conception Laboratoire de Biochimie Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Di Meglio","sequence":"additional","affiliation":[{"name":"APHM, H\u00f4pital Timone Enfants Service de Neurologie P\u00e9diatrique Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Albertini","sequence":"additional","affiliation":[{"name":"APHM, H\u00f4pital Timone Enfants Service de Neurologie P\u00e9diatrique Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Audic","sequence":"additional","affiliation":[{"name":"APHM, H\u00f4pital Timone Enfants Service de Neurologie P\u00e9diatrique Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Riccardi","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, U1251\u2010MMG, Marseille Medical Genetics Marseille France"},{"name":"APHM, H\u00f4pital Timone Enfants D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale Marseille France"},{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Boulay","sequence":"additional","affiliation":[{"name":"APHM, H\u00f4pital Timone Enfants Service de Neurologie P\u00e9diatrique Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Philip","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, U1251\u2010MMG, Marseille Medical Genetics Marseille France"},{"name":"APHM, H\u00f4pital Timone Enfants D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale Marseille France"},{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3339-9858","authenticated-orcid":false,"given":"Marc","family":"Bartoli","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, U1251\u2010MMG, Marseille Medical Genetics Marseille France"},{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"L\u00e9vy","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, U1251\u2010MMG, Marseille Medical Genetics Marseille France"},{"name":"APHM, H\u00f4pital Timone Enfants D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale Marseille France"},{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Krahn","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, U1251\u2010MMG, Marseille Medical Genetics Marseille France"},{"name":"APHM, H\u00f4pital Timone Enfants D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale Marseille France"},{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Chabrol","sequence":"additional","affiliation":[{"name":"GIPTIS (Genetics Institute for Patients, Therapies Innovation and Science) Marseille France"},{"name":"APHM, H\u00f4pital Timone Enfants Service de Neurologie P\u00e9diatrique Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2015.11.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.082370"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1427"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.027"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.299321"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.023"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010060713\u2010035546"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu545"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.10.006"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11922"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100305\u20101"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166066"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/301968"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/383357a0"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.65"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13086"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38406"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22965"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12876"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154584"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a002063"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165942"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.1277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1277","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T11:18:54Z","timestamp":1708514334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,14]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/mgg3.1277"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1277","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,14]]},"assertion":[{"value":"2019-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1277"}}