Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2091-11-39
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dc.titleSimilarity of molecular phenotype between known epilepsy gene LGI1 and disease candidate gene LGI2
dc.contributor.authorLimviphuvadh, V
dc.contributor.authorChua, L.L
dc.contributor.authorRahim, R.A.B
dc.contributor.authorEisenhaber, F
dc.contributor.authorMaurer-Stroh, S
dc.contributor.authorAdhikari, S.
dc.date.accessioned2020-09-04T06:37:26Z
dc.date.available2020-09-04T06:37:26Z
dc.date.issued2010
dc.identifier.citationLimviphuvadh, V, Chua, L.L, Rahim, R.A.B, Eisenhaber, F, Maurer-Stroh, S, Adhikari, S. (2010). Similarity of molecular phenotype between known epilepsy gene LGI1 and disease candidate gene LGI2. BMC Biochemistry 11 (1) : 39. ScholarBank@NUS Repository. https://doi.org/10.1186/1471-2091-11-39
dc.identifier.issn14712091
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174456
dc.description.abstractBackground. The LGI2 (leucine-rich, glioma inactivated 2) gene, a prime candidate for partial epilepsy with pericentral spikes, belongs to a family encoding secreted, beta-propeller domain proteins with EPTP/EAR epilepsy-associated repeats. In another family member, LGI1 (leucine-rich, glioma inactivated 1) mutations are responsible for autosomal dominant lateral temporal epilepsy (ADLTE). Because a few LGI1 disease mutations described in the literature cause secretion failure, we experimentally analyzed the secretion efficiency and subcellular localization of several LGI1 and LGI2 mutant proteins corresponding to observed non-synonymous single nucleotide polymorphisms (nsSNPs) affecting the signal peptide, the leucine-rich repeats and the EAR propeller. Results. Mapping of disease-causing mutations in the EAR domain region onto a 3D-structure model shows that many of these mutations co-localize at an evolutionary conserved surface region of the propeller. We find that wild-type LGI2 is secreted to the extracellular medium in glycosylated form similarly to LGI1, whereas several mutant proteins tested in this study are secretion-deficient and accumulate in the endoplasmic reticulum. Interestingly, mutations at structurally homologous positions in the EAR domain have the same effect on secretion in LGI1 and LGI2. Conclusions. This similarity of experimental mislocalization phenotypes for mutations at homologous positions of LGI2 and the established epilepsy gene LGI1 suggests that both genes share a potentially common molecular pathogenesis mechanism that might be the reason for genotypically distinct but phenotypically related forms of epilepsy. © 2010 Limviphuvadh et al; licensee BioMed Central Ltd.
dc.publisherBioMed Central Ltd.
dc.sourceUnpaywall 20200831
dc.subjectleucine rich glioma inactivated 1 protein
dc.subjectleucine rich glioma inactivated 2 protein
dc.subjectmutant protein
dc.subjectregulator protein
dc.subjectunclassified drug
dc.subjectLGI1 protein, human
dc.subjectLGI2 protein, human
dc.subjectprotein
dc.subjectarticle
dc.subjectcellular distribution
dc.subjectcontrolled study
dc.subjectconvergent evolution
dc.subjectendoplasmic reticulum
dc.subjectepilepsy
dc.subjectextracellular space
dc.subjectgene mapping
dc.subjectgene mutation
dc.subjectglycosylation
dc.subjecthuman
dc.subjecthuman cell
dc.subjectnucleotide sequence
dc.subjectphenotype
dc.subjectprotein domain
dc.subjectprotein secretion
dc.subjectprotein structure
dc.subjectsingle nucleotide polymorphism
dc.subjectwild type
dc.subjectchemistry
dc.subjectclassification
dc.subjectfocal epilepsy
dc.subjectgenetics
dc.subjectmissense mutation
dc.subjectphylogeny
dc.subjectprotein tertiary structure
dc.subjecttemporal lobe epilepsy
dc.subjectEpilepsies, Partial
dc.subjectEpilepsy, Temporal Lobe
dc.subjectHumans
dc.subjectMutation, Missense
dc.subjectPhenotype
dc.subjectPhylogeny
dc.subjectPolymorphism, Single Nucleotide
dc.subjectProtein Structure, Tertiary
dc.subjectProteins
dc.typeArticle
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.description.doi10.1186/1471-2091-11-39
dc.description.sourcetitleBMC Biochemistry
dc.description.volume11
dc.description.issue1
dc.description.page39
dc.published.statePublished
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