{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:07:04Z","timestamp":1790370424581,"version":"4.1.0"},"reference-count":21,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANIA Foundation","award":["21.31"],"award-info":[{"award-number":["21.31"]}]},{"name":"European Union\u2014Next Generation EU\u2014NRRP M6C2\u2014Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["21.31"],"award-info":[{"award-number":["21.31"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The use of NGS technology has rapidly increased during the last decade, and many new monogenic neurodevelopmental disorders have emerged. Pathogenic variants in the neuronal CAMK2A gene have been recently associated with \u201cintellectual developmental disorder, autosomal dominant 53\u2033 (OMIM#617798), a syndrome characterized by variable clinical manifestations including mild to severe intellectual disability, delayed psychomotor development, delayed or absent speech, delayed walking, seizures, dysmorphic features and behavioral psychiatric manifestations as autism spectrum disorders, aggressive behavior, and hyperactivity. CAMK2A (OMIM*114078) encodes for a subunit of the calcium\/calmodulin-dependent serine\/threonine kinase II (CaMKII), which is predominately expressed in the brain, where it plays critical roles in synaptic plasticity, learning, and memory as well as in neuronal migration. Methods and Results: We hereby describe a thirty-five-year-old woman affected by severe intellectual disability with epileptic encephalopathy. We performed exome sequencing and found a de novo heterozygous variant in the CAMK2A gene (NM_171825.2: c.874_876delCTT; p.Lys292del), which was fully correlated with her phenotype. This is the first report of an inframe single amino acid deletion in a patient affected by intellectual developmental disorder autosomal dominant 53. The variant is predicted to affect protein structure and function and interaction with other proteins and hits a crucial functional site. Discussion: We discuss our variant in relation to previously reported variants and with the objective of delineating possible genotype\u2013phenotype correlations.<\/jats:p>","DOI":"10.3390\/genes14071353","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deletion of a Single Lysine Residue at Position 292 of CAMK2A Disrupts Protein Function, Causing Severe Epileptic Encephalopathy and Intellectual Disability"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-8554","authenticated-orcid":false,"given":"Carla","family":"Lintas","sequence":"first","affiliation":[{"name":"Research Unit of Medical Genetics, Department of Medicine, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy"},{"name":"Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-4912","authenticated-orcid":false,"given":"Angelo","family":"Facchiano","sequence":"additional","affiliation":[{"name":"CNR-ISA National Research Council, Institute of Food Sciences Istituto di Scienze dell\u2019Alimentazione\u2014Consiglio Nazionale delle Ricerche, Via Roma 64, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-6687","authenticated-orcid":false,"given":"Alessia","family":"Azzar\u00e0","sequence":"additional","affiliation":[{"name":"Research Unit of Medical Genetics, Department of Medicine, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-4249","authenticated-orcid":false,"given":"Ilaria","family":"Cassano","sequence":"additional","affiliation":[{"name":"Research Unit of Medical Genetics, Department of Medicine, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-285X","authenticated-orcid":false,"given":"Claudio","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Research Coordination and Support Service, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Galasso","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Systems Medicine Department, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6775-5972","authenticated-orcid":false,"given":"Fiorella","family":"Gurrieri","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1523\/JNEUROSCI.2068-16.2017","article-title":"A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors","volume":"37","author":"Stephenson","year":"2017","journal-title":"J. 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