{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:30:07Z","timestamp":1790476207944,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP15113"],"award-info":[{"award-number":["GGP15113"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1861419N"],"award-info":[{"award-number":["1861419N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS069605"],"award-info":[{"award-number":["R01 NS069605"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS49119"],"award-info":[{"award-number":["R01 NS49119"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U54 NS108874"],"award-info":[{"award-number":["U54 NS108874"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Recent reports have described single individuals with neurodevelopmental disability (NDD) harboring heterozygous\n                      <jats:italic>KCNQ3<\/jats:italic>\n                      de novo variants (DNVs). We sought to assess whether pathogenic variants in\n                      <jats:italic>KCNQ3<\/jats:italic>\n                      cause NDD and to elucidate the associated phenotype and molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with NDD and\n                      <jats:italic>KCNQ3<\/jats:italic>\n                      DNVs were identified through an international collaboration. Phenotypes were characterized by clinical assessment, review of charts, electroencephalographic (EEG) recordings, and parental interview. Functional consequences of variants were analyzed in vitro by patch\u2010clamp recording.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven patients were assessed. They had recurrent heterozygous DNVs in\n                      <jats:italic>KCNQ3<\/jats:italic>\n                      affecting residues R230 (R230C, R230H, R230S) and R227 (R227Q). All patients exhibited global developmental delay within the first 2 years of life. Most (8\/11, 73%) were nonverbal or had a few words only. All patients had autistic features, and autism spectrum disorder (ASD) was diagnosed in 5 of 11 (45%). EEGs performed before 10 years of age revealed frequent sleep\u2010activated multifocal epileptiform discharges in 8 of 11 (73%). For 6 of 9 (67%) recorded between 1.5 and 6 years of age, spikes became near\u2010continuous during sleep. Interestingly, most patients (9\/11, 82%) did not have seizures, and no patient had seizures in the neonatal period. Voltage\u2010clamp recordings of the mutant KCNQ3 channels revealed gain\u2010of\u2010function (GoF) effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Specific GoF variants in\n                      <jats:italic>KCNQ3<\/jats:italic>\n                      cause NDD, ASD, and abundant sleep\u2010activated spikes. This new phenotype contrasts both with self\u2010limited neonatal epilepsy due to\n                      <jats:italic>KCNQ3<\/jats:italic>\n                      partial loss of function, and with the neonatal or infantile onset epileptic encephalopathies due to\n                      <jats:italic>KCNQ2<\/jats:italic>\n                      GoF. ANN NEUROL 2019;86:181\u2013192\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25522","type":"journal-article","created":{"date-parts":[[2019,6,9]],"date-time":"2019-06-09T02:29:24Z","timestamp":1560047364000},"page":"181-192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Autism and developmental disability caused by\n                    <i>KCNQ3<\/i>\n                    gain\u2010of\u2010function variants"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7285-1195","authenticated-orcid":false,"given":"Tristan T.","family":"Sands","sequence":"first","affiliation":[{"name":"Department of Neurology Columbia University Medical Center  New York NY"},{"name":"Institute for Genomic Medicine Columbia University Medical Center  New York 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