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Open AccessCase Report

Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome

1
Molecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 30007 Salamanca, Spain
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Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 30007 Salamanca, Spain
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Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain
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Biosciences Research Institute, School of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain
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Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
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Instituto Pediátrico de Enfermedades Raras (IPER), Hospital Sant Joan de Déu, 08950 Barcelona, Spain
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Instituto de Biofísica, Consejo Superior de Investigaciones Científicas (CSIC), Universidad del País Vasco, 48940 Bilbao, Spain
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Unidad de Genética Molecular, Departamento de Medicina, Universidad de Salamanca, 37008 Salamanca, Spain
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Neurology Department, Hospital Sant Joan de Déu, Sant Joan de Déu Research Institute and CIBERER, Instituto de Salud Carlos III, 08950 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4447; https://doi.org/10.3390/ijms21124447
Received: 20 May 2020 / Revised: 17 June 2020 / Accepted: 18 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue Macromolecular Modeling to Understand Genetic Disorders)
Complex neurodevelopmental syndromes frequently have an unknown etiology, in which genetic factors play a pathogenic role. 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. View Full-Text
Keywords: epilepsy; dystonia; cerebral palsy; neuromotor delay; KCNQ2 epilepsy; dystonia; cerebral palsy; neuromotor delay; KCNQ2
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MDPI and ACS Style

Lazo, P.A.; García, J.L.; Gómez-Puertas, P.; Marcos-Alcalde, Í.; Arjona, C.; Villarroel, A.; González-Sarmiento, R.; Fons, C. Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome. Int. J. Mol. Sci. 2020, 21, 4447.

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