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Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Jun 23; Vol. 21 (12). Date of Electronic Publication: 2020 Jun 23. - Publication Year :
- 2020
-
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 :
- Child
Developmental Disabilities complications
Developmental Disabilities genetics
Epileptic Syndromes complications
Epileptic Syndromes genetics
Humans
Male
Neurodevelopmental Disorders complications
Neurodevelopmental Disorders genetics
Phenotype
Prognosis
Developmental Disabilities pathology
Epileptic Syndromes pathology
Exons
Gene Duplication
KCNQ2 Potassium Channel genetics
Mutation
Neurodevelopmental Disorders pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Report
- Accession number :
- 32585800
- Full Text :
- https://doi.org/10.3390/ijms21124447