{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:14:04Z","timestamp":1790136844629,"version":"4.0.1"},"reference-count":41,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["GODAFIT Strategic Positioning Fund"],"award-info":[{"award-number":["GODAFIT Strategic Positioning Fund"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Calcium\/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay, seizures and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in\n                    <jats:italic>CAMK2A<\/jats:italic>\n                    . The missense mutation, p.His477Tyr is located in the CAMK2A association domain that is critical for its function and localization. Biochemically, the p.His477Tyr mutant is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , CAMK2A\n                    <jats:sup>H477Y<\/jats:sup>\n                    failed to rescue neuronal defects in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    lacking\n                    <jats:italic>unc-43<\/jats:italic>\n                    , the ortholog of human\n                    <jats:italic>CAMK2A. In vitro<\/jats:italic>\n                    , neurons derived from patient iPSCs displayed profound synaptic defects. Together, our data demonstrate that a recessive germline mutation in\n                    <jats:italic>CAMK2A<\/jats:italic>\n                    leads to neurodevelopmental defects in humans and suggest that dysfunctional CAMK2 paralogs may contribute to other neurological disorders.\n                  <\/jats:p>","DOI":"10.7554\/elife.32451","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T20:00:55Z","timestamp":1526932855000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.32451","source":"Crossref","is-referenced-by-count":70,"title":["A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-112X","authenticated-orcid":true,"given":"Poh Hui","family":"Chia","sequence":"first","affiliation":[{"name":"Institute of Medical Biology, Immunos, 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