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This study utilizes whole-exome sequencing (WES) to examine four members of a family with a son presenting, since birth, with epileptic-like crises, combined with cerebral palsy, severe neuromotor and developmental delay, dystonic tetraparexia, axonal motor affectation, and hyper-excitability of unknown origin. The WES study detected within the patient a de novo heterozygous in-frame duplication of thirty-six nucleotides within exon 7 of the human KCNQ2 gene. This insertion duplicates the first twelve amino acids of the calmodulin binding site I. Molecular dynamics simulations of this KCNQ2 peptide duplication, modelled on the 3D structure of the KCNQ2 protein, suggest that the duplication may lead to the dysregulation of calcium inhibition of this protein function.<\/jats:p>","DOI":"10.3390\/ijms21124447","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T06:11:02Z","timestamp":1592892662000},"page":"4447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8997-3025","authenticated-orcid":false,"given":"Pedro A.","family":"Lazo","sequence":"first","affiliation":[{"name":"Molecular Mechanisms of Cancer Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad de Salamanca, 30007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 30007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-5726","authenticated-orcid":false,"given":"Juan L.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Molecular Mechanisms of Cancer Program, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad de Salamanca, 30007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 30007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-729X","authenticated-orcid":false,"given":"Paulino","family":"G\u00f3mez-Puertas","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-Universidad Aut\u00f3noma de Madrid, Cantoblanco, E-28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0674-6423","authenticated-orcid":false,"given":"\u00cd\u00f1igo","family":"Marcos-Alcalde","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC-Universidad Aut\u00f3noma de Madrid, Cantoblanco, E-28049 Madrid, Spain"},{"name":"Biosciences Research Institute, School of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-8724","authenticated-orcid":false,"given":"Cesar","family":"Arjona","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, Esplugues de Llobregat, 08950 Barcelona, Spain"},{"name":"Instituto Pedi\u00e1trico de Enfermedades Raras (IPER), Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Villarroel","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad del Pa\u00eds Vasco, 48940 Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2726-6795","authenticated-orcid":false,"given":"Rogelio","family":"Gonz\u00e1lez-Sarmiento","sequence":"additional","affiliation":[{"name":"Molecular Mechanisms of Cancer Program, 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