{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:21:03Z","timestamp":1791260463517,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20dm0107085h0005"],"award-info":[{"award-number":["20dm0107085h0005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The molecular mechanisms underlying neurodevelopmental disorders (NDDs) remain unclear. We previously identified Down syndrome cell adhesion molecule like 1 (<jats:italic>Dscaml1<\/jats:italic>) as a responsible gene for Ihara epileptic rat (IER), a rat model for human NDDs with epilepsy. However, the relationship between NDDs and <jats:italic>DSCAML1<\/jats:italic> in humans is still elusive. In this study, we screened databases of autism spectrum disorders (ASD), intellectual disability (ID)\/developmental disorders (DD) and schizophrenia for genomic mutations in human <jats:italic>DSCAML1<\/jats:italic>. We then performed <jats:italic>in silico<\/jats:italic> analyses to estimate the potential damage to the mutated DSCAML1 proteins and chose three representative mutations (DSCAML1<jats:sup>C729R<\/jats:sup>, DSCAML1<jats:sup>R1685*<\/jats:sup> and DSCAML1<jats:sup>K2108Nfs*37<\/jats:sup>), which lacked a cysteine residue in the seventh Ig domain, the intracellular region and the C\u2010terminal PDZ\u2010binding motif, respectively. In overexpression experiments in a cell line, DSCAML1<jats:sup>C729R<\/jats:sup> lost its mature N\u2010glycosylation, whereas DSCAML1<jats:sup>K2108Nfs*37<\/jats:sup> was abnormally degraded via proteasome\u2010dependent protein degradation. Furthermore, in primary hippocampal neurons, the ability of the wild\u2010type DSCAML1 to regulate the number of synapses was lost with all mutant proteins. These results provide insight into understanding the roles of the domains in the DSCAML1 protein and further suggest that these mutations cause functional changes, albeit through different mechanisms, that likely affect the pathophysiology of NDDs.<\/jats:p>","DOI":"10.1111\/gtc.12831","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:48:38Z","timestamp":1611751718000},"page":"136-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Potential involvement of <i>DSCAML1<\/i> mutations in neurodevelopmental disorders"],"prefix":"10.1111","volume":"26","author":[{"given":"Shigehiro","family":"Ogata","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cellular Biology National Institute of Neuroscience NCNP Tokyo Japan"},{"name":"Department of Psychiatry and Behavioral Sciences Tokyo Medical and Dental University Graduate School Tokyo 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