Is LGI2 the candidate gene for partial epilepsy with pericentral spikes?
Partial epilepsy with pericentral spikes (PEPS) is a familial epilepsy with disease locus mapped to human chromosome region 4p15; yet, the causative gene is unknown. In this work, arguments based on protein sequence analysis and patient-specific chromosomal deletions are provided for LGI2 as the prime candidate gene for PEPS among the 52 genes known at the genome locus 4p15. Furthermore, we suggest that two reports of patients that were not classified as PEPS but show very similar phenotypes and deletions in the PEPS disease locus, could in fact describe the same disease. To test this hypothesis, patients with diagnosed PEPS or the described similar phenotypes could be screened for mutations in LGI2 and other shortlisted candidate genes. The linkage between PEPS and its disease causing gene(s) would allow diagnosis of the disease based on genetic screening as well as hereditary studies. Furthermore, previous knowledge on molecular disease mechanisms of related LGI proteins, for example LGI1 and autosomal dominant lateral temporal epilepsy, could be applied to deepen the understanding of the PEPS disease mechanism at the molecular level, which may facilitate therapeutic intervention in the future. Supplementary Table is available at http://www.worldscinet.com/jbcb/.
Limviphuvadh
Vachiranee
V
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, Singapore 138671, Singapore. vachiraneel@bii.a-star.edu.sg
Chua
Ling Ling
LL
Eisenhaber
Frank
F
Adhikari
Sharmila
S
Maurer-Stroh
Sebastian
S
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D019295:Computational Biology; D004828:Epilepsies, Partial / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment
C456923:LGI2 protein, human; D011506:Proteins