{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:17Z","timestamp":1772160077988,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    SCY1\u2010like protein 2 (\n                    <jats:italic>SCYL2<\/jats:italic>\n                    ) is a member of the SCY1\u2010like pseudokinase family which regulates secretory protein trafficking. It plays a crucial role in the nervous system by suppressing excitotoxicity in the developing brain.\n                    <jats:italic>Scyl2<\/jats:italic>\n                    knockout mice have excess prenatal mortality and survivors show severe neurological dysfunction. Bi\u2010allelic loss\u2010of\u2010function (LOF) variants in\n                    <jats:italic>SCYL2<\/jats:italic>\n                    were recently associated with arthrogryposis multiplex congenita\u20104 (AMC4) following the report of 6 individuals from two consanguineous unrelated families. The AMC4 phenotype described included severe arthrogryposis, corpus callosum agenesis, epilepsy and frequently, early death. We describe here two additional similarly affected individuals with AMC4, including one diagnosed in the prenatal period, with bi\u2010allelic LOF variants in\n                    <jats:italic>SCYL2<\/jats:italic>\n                    , and two individuals homozygous for missense variants in the protein kinase domain of\n                    <jats:italic>SCYL2<\/jats:italic>\n                    and presenting with developmental delay only. Our study confirms the association of\n                    <jats:italic>SCYL2<\/jats:italic>\n                    with AMC4 and suggests a milder phenotype can occur, extending the phenotypic spectrum of autosomal recessive\n                    <jats:italic>SCYL2<\/jats:italic>\n                    \u2010related disorders.\n                  <\/jats:p>","DOI":"10.1111\/cge.14608","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T02:28:50Z","timestamp":1724293730000},"page":"757-763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>SCYL2<\/scp>\n                    \u2010related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita\u20104 and beyond?"],"prefix":"10.1111","volume":"106","author":[{"given":"Marl\u00e8ne","family":"Malbos","sequence":"first","affiliation":[{"name":"CRMRs \"Anomalies du D\u00e9veloppement et syndromes malformatifs\" et \"D\u00e9ficiences Intellectuelles de causes rares\", FHU\u2010TRANSLAD, CHU Dijon Bourgogne  Dijon France"},{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Vera","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Genetics and Reference Center for Developmental Abnormalities Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-0971","authenticated-orcid":false,"given":"Harsh","family":"Sheth","sequence":"additional","affiliation":[{"name":"FRIGE's Institute of Human Genetics  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhonda E.","family":"Schnur","sequence":"additional","affiliation":[{"name":"Cooper Medical School of Rowan University\/Cooper University Health Care  Camden New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lien","family":"Juven","sequence":"additional","affiliation":[{"name":"CRMRs \"Anomalies du D\u00e9veloppement et syndromes malformatifs\" et \"D\u00e9ficiences Intellectuelles de causes rares\", FHU\u2010TRANSLAD, CHU Dijon Bourgogne  Dijon France"},{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Claire","family":"Brehin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Genetics and Reference Center for Developmental Abnormalities Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayesh","family":"Sheth","sequence":"additional","affiliation":[{"name":"FRIGE's Institute of Human Genetics  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajit","family":"Gandhi","sequence":"additional","affiliation":[{"name":"FRIGE's Institute of Human Genetics  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faye L.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Cooper Medical School of Rowan University\/Cooper University Health Care  Camden New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-465X","authenticated-orcid":false,"given":"Ange\u2010Line","family":"Bruel","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"},{"name":"Inserm UMR1231 GAD, Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9, FHU TRANSLAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florent","family":"Marguet","sequence":"additional","affiliation":[{"name":"Department of Pathology, Department of Genetics and Reference Center for Developmental Abnormalities Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Begtrup","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin G.","family":"Monaghan","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Safraou","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"},{"name":"Inserm UMR1231 GAD, Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9, FHU TRANSLAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Brasseur\u2010Daudruy","sequence":"additional","affiliation":[{"name":"Radiologie p\u00e9diatrique CHU de Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric Tran","family":"Mau\u2010Them","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"},{"name":"Inserm UMR1231 GAD, Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9, FHU TRANSLAD  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannis","family":"Duffourd","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[{"name":"CRMRs \"Anomalies du D\u00e9veloppement et syndromes malformatifs\" et \"D\u00e9ficiences Intellectuelles de causes rares\", FHU\u2010TRANSLAD, CHU Dijon Bourgogne  Dijon France"},{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christel","family":"Thauvin\u2010Robinet","sequence":"additional","affiliation":[{"name":"CRMRs \"Anomalies du D\u00e9veloppement et syndromes malformatifs\" et \"D\u00e9ficiences Intellectuelles de causes rares\", FHU\u2010TRANSLAD, CHU Dijon Bourgogne  Dijon France"},{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Benke","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics Joe DiMaggio Children's Hospital  Hollywood Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Philippe","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9nomique M\u00e9dicale, UF Innovation en diagnostic g\u00e9nomique des maladies rares CHU Dijon Bourgogne  Dijon France"},{"name":"Inserm UMR1231 GAD, Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9, FHU TRANSLAD  Dijon France"},{"name":"Laboratoire de G\u00e9n\u00e9tique CHR Metz\u2010Thionville, H\u00f4pital Mercy  Metz France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.03.008"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20738"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84457"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502462200"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2007.00576.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2056-14.2015"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.17.00824"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.10.011"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.260"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02117-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-060591"}],"container-title":["Clinical 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