Mutation Analysis of the Leucine-Rich, Glioma Inactivated 1 Gene (LGI1) in Japanese Febrile Seizure Patients

Abstract

Mutations in the leucine-rich, glioma inactivated 1 gene (LGI1) were recently identified in some families with autosomal dominant lateral temporal epilepsy (ADLTE). To investigate whether the LGI1 gene is a susceptibility gene for febrile seizures (FS), we performed a systematic search for mutations in 94 unrelated Japanese patients with FS. We detected two intronic polymorphisms (IVS2 + 19 A/G and IVS6 - 18 T/C). No non-synonymous mutation was detected. We genotyped these polymorphisms and performed a case-control study and transmission disequilibrium testing (TDT) of 62 FS families (n = 230) and 105 control subjects. None of the polymorphisms was significantly associated with FS. Our results indicate that genomic variations in the LGI1 gene are not likely to be substantially involved in the etiology of FS in the Japanese population.

Key words

Febrile seizures - the LGI1 gene - genetics - mutation - association - Japanese

References

• 1 Baram T Z, Shinnar S. Febrile Seizures. 1st ed. San Diego; Academic Press 2002
• 2 Freeman J M. Consensus statement-febrile seizures: a consensus of their significance, evaluation, and treatment.  Pediatrics. 1980;  66 1009-1012
• 3 Gu W, Brodtkorb E, Steinlein O K. LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures.  Ann Neurol. 2002;  52 364-367
• 4 Kalachikov S, Evgrafov O, Ross B, Winawer M, Barker-Cummings C, Boneschi F M. et al . Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.  Nat Genet. 2002;  30 335-341
• 5 Morante-Redolat J M, Gorostidi-Pagola A, Piquer-Sirerol S, Saenz A, Poza J J, Galan J. et al . Mutations in the LGI1/Epitempin gene on 10 q24 cause autosomal dominant lateral temporal epilepsy.  Hum Mol Genet. 2002;  11 1119-1128
• 6 Nakayama J, Fu Y H, Clark A M, Nakahara S, Hamano K, Iwasaki N. et al . A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures.  Ann Neurol. 2002;  52 654-657
• 7 Scheel H, Tomiuk S, Hofmann K. A common protein interaction domain links two recently identified epilepsy genes.  Hum Mol Genet. 2002;  11 1757-1762
• 8 Scheffer I E, Berkovic S F. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes.  Brain. 1997;  120 479-490
• 9 Skradski S L, Clark A M, Jiang H, White H S, Fu Y H, Ptacek L J. A novel gene causing a mendelian audiogenic mouse epilepsy.  Neuron. 2001;  31 537-544
• 10 Staub E, Perez-Tur J, Siebert R, Nobile C, Moschonas N K, Deloukas P. et al . The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders.  Trends Biochem Sci. 2002;  27 441-444