{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T21:54:23Z","timestamp":1776462863595,"version":"3.51.2"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T00:00:00Z","timestamp":1458000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHA1261\/4\u20101 and CRC1080"],"award-info":[{"award-number":["SCHA1261\/4\u20101 and CRC1080"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,1]]},"abstract":"L1CAM<\/jats:styled-content><\/jats:italic> gene mutations cause neurodevelopmental disorders collectively termed L1<\/jats:styled-content> syndrome. Insufficient information about L1CAM<\/jats:styled-content><\/jats:italic> variants complicates clinical prognosis, genetic diagnosis and genetic counseling. We combined clinical data, in silico<\/jats:italic> effect predictions and functional analysis of four L1CAM<\/jats:styled-content><\/jats:italic> variants, p.I37N, p.T38M, p.M172I and p.D202Y, located to the two N\u2010terminal Ig\u2010like domains present in five families with symptoms of L1<\/jats:styled-content> syndrome. Software tools predicted destabilizing effects of p.I37N<\/jats:styled-content> and p.D202Y<\/jats:styled-content> but results for p.T38M<\/jats:styled-content> and p.M172I<\/jats:styled-content> were inconsistent. Cell surface expression of mutant proteins L1\u2010T38M<\/jats:styled-content>, L1\u2010M172I<\/jats:styled-content> and L1\u2010D202Y<\/jats:styled-content> was normal. Conversely, L1\u2010I37N<\/jats:styled-content> accumulated in the endoplasmic reticulum (ER) and showed temperature\u2010sensitive protein maturation suggesting that p.I37N<\/jats:styled-content> induces protein misfolding. L1CAM<\/jats:styled-content>\u2010mediated cell\u2013cell aggregation was severely impaired by L1CAM<\/jats:styled-content><\/jats:italic> variants p.I37N<\/jats:styled-content>, p.M172I<\/jats:styled-content> and p.D202Y<\/jats:styled-content> but was preserved by the variant p.T38M<\/jats:styled-content>. Our experimental data indicate that protein misfolding and accumulation in the ER affect function of the L1CAM<\/jats:styled-content><\/jats:italic> variant p.I37N<\/jats:styled-content> whereas the variants p.M172I<\/jats:styled-content> and p.D202Y<\/jats:styled-content> impair homophilic interaction at the cell surface.<\/jats:p>","DOI":"10.1111\/cge.12763","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T21:29:42Z","timestamp":1455830982000},"page":"115-120","source":"Crossref","is-referenced-by-count":15,"title":["L1<\/scp> syndrome diagnosis complemented with functional analysis of L1CAM<\/scp> variants located to the two N\u2010terminal Ig\u2010like domains"],"prefix":"10.1111","volume":"91","author":[{"given":"W. A. A.","family":"Christaller","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University Medical Center Johannes Gutenberg\u2010University Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Centre Groningen University of Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Gebre\u2010Medhin","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Hospital, Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. M. W.","family":"Hofstra","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University of Rotterdam Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. K. E.","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Medical Center Johannes Gutenberg\u2010University Mainz Mainz Germany"},{"name":"Focus program Translational Neurosciences (FTN) Johannes Gutenberg\u2010University Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2741\/1108"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21172"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.071688"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.05.029"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-011-0307-4"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380001500407"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/358761a0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.1.1"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp325"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12015"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00993.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2012.44.7.050"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.180281"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.04.004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-015-2560-2"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.191"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.189"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12763","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12763","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:08:26Z","timestamp":1696291706000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,15]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/cge.12763"],"URL":"https:\/\/doi.org\/10.1111\/cge.12763","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,15]]}}}