LGI1 mutations in autosomal dominant partial epilepsy with auditory features.
OBJECTIVE
S: Mutations in LGI1 cause autosomal dominant partial epilepsy with auditory features (ADPEAF), a form of familial temporal lobe epilepsy with auditory ictal manifestations. The authors aimed to determine what proportion of ADPEAF families carries a mutation, to estimate the penetrance of identified mutations, and to identify clinical features that distinguish families with and without mutations.


METHODS
The authors sequenced LGI1 in 10 newly described ADPEAF families and analyzed clinical features in these families and others with mutations reported previously.


RESULTS
Three of the families had missense mutations in LGI1 (C42R, I298T, and A110D). Penetrance was 54% in eight families with LGI1 mutations the authors have identified so far (five reported previously and three reported here). Excluding the original linkage family, the authors have found mutations in 50% (7/14) of tested families. Families with and without mutations had similar clinical features, but those with mutations contained significantly more subjects with auditory symptoms and significantly fewer with autonomic symptoms. In families with mutations, the most common auditory symptom type was simple, unformed sounds (e.g., buzzing and ringing). In two of the newly identified families with mutations, some subjects with mutations had idiopathic generalized epilepsies.


CONCLUSIONS
LGI1 mutations are a common cause of autosomal dominant partial epilepsy with auditory features. Current data do not reveal a clinical feature that clearly predicts which families with autosomal dominant partial epilepsy with auditory features have a mutation. Some families with LGI1 mutations contain individuals with idiopathic generalized epilepsies. This could result from either an effect of LGI1 on risk for generalized epilepsy or an effect of co-occurring idiopathic generalized epilepsy-specific genes in these families.
Ottman
R
R
Gertrude H. Sergievsky Center, Columbia University, New York, NY 10032, USA. ro6@columbia.edu
Winawer
M R
MR
Kalachikov
S
S
Barker-Cummings
C
C
Gilliam
T C
TC
Pedley
T A
TA
Hauser
W A
WA
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D020937:Epilepsy, Partial, Sensory / Q000175:diagnosis / Q000235:genetics*; D005190:Family; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012306:Risk; D013577:Syndrome
D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins