d01338e2cac012d757352b3629c30724 pmc_32585800.pdf 7e01f953b9140bd70ecf7c5c69f12151bfcc2835 pmc_32585800.pdf 3b25ebd88d6dbe612f142e79c62e8daf7238f4571a3cc6a897f8b72897731d84 pmc_32585800.pdf Title: Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome Subject: 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. Keywords: epilepsy; dystonia; cerebral palsy; neuromotor delay; KCNQ2 Author: Pedro A. Lazo, Juan L. García, Paulino Gómez-Puertas, Íñigo Marcos-Alcalde, Cesar Arjona, Alvaro Villarroel, Rogelio González-Sarmiento and Carmen Fons Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Tue Jun 23 06:31:58 2020 CEST ModDate: Tue Jun 23 06:31:58 2020 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1426684 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BXJXTL+URWPalladioL-Ital Type 1 Custom yes yes no 73 0 XBZZZN+URWPalladioL-Bold Type 1 Custom yes yes no 74 0 XVXMNT+VnURWPalladioL-Bold Type 1 Custom yes yes no 75 0 XYYYTW+URWPalladioL-Roma Type 1 Custom yes yes no 76 0 ESNFFO+VnURWPalladioL Type 1 Custom yes yes no 77 0 FESXTA+Rpxr Type 1 Builtin yes yes no 78 0 CKUPDE+TimesNewRomanPS-BoldItalicMT 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