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- Title
Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome.
- Authors
Lazo, Pedro A.; García, Juan L.; Gómez-Puertas, Paulino; Marcos-Alcalde, Íñigo; Arjona, Cesar; Villarroel, Alvaro; González-Sarmiento, Rogelio; Fons, Carmen
- Abstract
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.
- Subjects
CALMODULIN; CEREBRAL palsy; DEVELOPMENTAL delay; MOLECULAR dynamics; ETIOLOGY of diseases; PROTEIN structure
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 12, p4447
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21124447