Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2091-11-39
Title: Similarity of molecular phenotype between known epilepsy gene LGI1 and disease candidate gene LGI2
Authors: Limviphuvadh, V
Chua, L.L
Rahim, R.A.B
Eisenhaber, F 
Maurer-Stroh, S 
Adhikari, S.
Keywords: leucine rich glioma inactivated 1 protein
leucine rich glioma inactivated 2 protein
mutant protein
regulator protein
unclassified drug
LGI1 protein, human
LGI2 protein, human
protein
article
cellular distribution
controlled study
convergent evolution
endoplasmic reticulum
epilepsy
extracellular space
gene mapping
gene mutation
glycosylation
human
human cell
nucleotide sequence
phenotype
protein domain
protein secretion
protein structure
single nucleotide polymorphism
wild type
chemistry
classification
focal epilepsy
genetics
missense mutation
phylogeny
protein tertiary structure
temporal lobe epilepsy
Epilepsies, Partial
Epilepsy, Temporal Lobe
Humans
Mutation, Missense
Phenotype
Phylogeny
Polymorphism, Single Nucleotide
Protein Structure, Tertiary
Proteins
Issue Date: 2010
Publisher: BioMed Central Ltd.
Citation: Limviphuvadh, 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
Abstract: Background. 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.
Source Title: BMC Biochemistry
URI: https://scholarbank.nus.edu.sg/handle/10635/174456
ISSN: 14712091
DOI: 10.1186/1471-2091-11-39
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