LGI1 mutations in temporal lobe epilepsies.

Abstract:

BACKGROUND AND OBJECTIVES:A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) have been found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). The authors aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF, and to examine the role of LGI1 paralogs in ADPEAF without LGI1 mutations. METHODS:The authors performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3, and LGI4. RESULTS:Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, two had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in two of four ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c.124T-->G; C42G) and 8 (c.1418C-->T; S473L). No mutations in LGI2, LGI3, or LGI4 were found in the other two ADPEAF families. CONCLUSION:In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3, or LGI4 did not account for families without LGI1 mutations.

journal_name

Neurology

journal_title

Neurology

authors

Berkovic SF,Izzillo P,McMahon JM,Harkin LA,McIntosh AM,Phillips HA,Briellmann RS,Wallace RH,Mazarib A,Neufeld MY,Korczyn AD,Scheffer IE,Mulley JC

doi

10.1212/01.wnl.0000118213.94650.81

subject

Has Abstract

pub_date

2004-04-13 00:00:00

pages

1115-9

issue

7

eissn

0028-3878

issn

1526-632X

journal_volume

62

pub_type

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