| http://purl.uniprot.org/citations/29844171 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29844171 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29844171 | http://www.w3.org/2000/01/rdf-schema#comment | "De novo variants in SCN2A developmental and epileptic encephalopathy (DEE) show distinctive genotype-phenotype correlations. The two most recurrent SCN2A variants in DEE, R1882Q and R853Q, are associated with different ages and seizure types at onset. R1882Q presents on day 1 of life with focal seizures, while infantile spasms is the dominant seizure type seen in R853Q cases, presenting at a median age of 8 months. Voltage clamp, which characterizes the functional properties of ion channels, predicted gain-of-function for R1882Q and loss-of-function for R853Q. Dynamic action potential clamp, that we implement here as a method for modeling neurophysiological consequences of a given epilepsy variant, predicted that the R1882Q variant would cause a dramatic increase in firing, whereas the R853Q variant would cause a marked reduction in action potential firing. Dynamic clamp was also able to functionally separate the L1563V variant, seen in benign familial neonatal-infantile seizures from R1882Q, seen in DEE, suggesting a diagnostic potential for this type of analysis. Overall, the study shows a strong correlation between clinical phenotype, SCN2A genotype, and functional modeling. Dynamic clamp is well positioned to impact our understanding of pathomechanisms and for development of disease mechanism-targeted therapies in genetic epilepsy."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1800077115"xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1800077115"xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Berkovic S.F."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Berkovic S.F."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Scheffer I.E."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Scheffer I.E."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Howell K.B."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Howell K.B."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Petrou S."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Petrou S."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Berecki G."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Berecki G."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Kaplan D."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Kaplan D."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Cilio M.R."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Cilio M.R."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Deerasooriya Y.H."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Deerasooriya Y.H."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Oliva M.K."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/author | "Oliva M.K."xsd:string |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29844171 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |