Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/12/4447 |
| _version_ | 1797564407255924736 |
|---|---|
| author | Pedro A. Lazo Juan L. García Paulino Gómez-Puertas Íñigo Marcos-Alcalde Cesar Arjona Alvaro Villarroel Rogelio González-Sarmiento Carmen Fons |
| author_facet | Pedro A. Lazo Juan L. García Paulino Gómez-Puertas Íñigo Marcos-Alcalde Cesar Arjona Alvaro Villarroel Rogelio González-Sarmiento Carmen Fons |
| author_sort | Pedro A. Lazo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:56:55Z |
| format | Article |
| id | doaj.art-03fc879969354257aa2b9e14a8a6a498 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:56:55Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-03fc879969354257aa2b9e14a8a6a4982023-11-20T04:39:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112444710.3390/ijms21124447Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay SyndromePedro A. Lazo0Juan L. García1Paulino Gómez-Puertas2Íñigo Marcos-Alcalde3Cesar Arjona4Alvaro Villarroel5Rogelio González-Sarmiento6Carmen Fons7Molecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 30007 Salamanca, SpainMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 30007 Salamanca, SpainCentro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, SpainCentro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, SpainInstitut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, SpainInstituto de Biofísica, Consejo Superior de Investigaciones Científicas (CSIC), Universidad del País Vasco, 48940 Bilbao, SpainMolecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 30007 Salamanca, SpainInstitut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, SpainComplex 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.https://www.mdpi.com/1422-0067/21/12/4447epilepsydystoniacerebral palsyneuromotor delayKCNQ2 |
| spellingShingle | Pedro A. Lazo Juan L. García Paulino Gómez-Puertas Íñigo Marcos-Alcalde Cesar Arjona Alvaro Villarroel Rogelio González-Sarmiento Carmen Fons Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome International Journal of Molecular Sciences epilepsy dystonia cerebral palsy neuromotor delay KCNQ2 |
| title | Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome |
| title_full | Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome |
| title_fullStr | Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome |
| title_full_unstemmed | Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome |
| title_short | Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome |
| title_sort | novel dominant kcnq2 exon 7 partial in frame duplication in a complex epileptic and neurodevelopmental delay syndrome |
| topic | epilepsy dystonia cerebral palsy neuromotor delay KCNQ2 |
| url | https://www.mdpi.com/1422-0067/21/12/4447 |
| work_keys_str_mv | AT pedroalazo noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT juanlgarcia noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT paulinogomezpuertas noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT inigomarcosalcalde noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT cesararjona noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT alvarovillarroel noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT rogeliogonzalezsarmiento noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome AT carmenfons noveldominantkcnq2exon7partialinframeduplicationinacomplexepilepticandneurodevelopmentaldelaysyndrome |