Abnormal phonologic processing in familial lateral temporal lobe epilepsy due to a new LGI1 mutation.
OBJECTIVE
Autosomal dominant lateral temporal lobe epilepsy (ADLTLE) is a rare familial epilepsy with onset in adolescence or early adulthood, associated with mutations of LGI1 in most families. We describe the clinical, neuropsychological, and molecular genetic study of a new ADLTLE Italian family.


METHODS
A four-generation family from Sardinia was studied. Clinical, neuropsychological, and genetic analysis were performed in eight living affected family members.


RESULTS
Nine family members had seizures over four generations; four of them had auditory auras and aphasia followed by secondarily generalized tonic-clonic seizures (SGTCs). One individual in addition had visual symptoms, and one family member had only vertigo followed by SGTCs. The side of seizure onset could not be determined in these five patients with focal seizures. The proband had febrile and afebrile tonic-clonic seizures. Two family members had only febrile seizures. Inheritance was autosomal dominant with 59% penetrance. Genetic molecular analysis showed a new LGI1 missense mutation causing a Leu154Pro substitution in six affected and one unaffected individuals. Dichotic listening performance was abnormal in four affected individuals compared with controls. Fluency and lexical abilities also were pathological in three patients. These findings showed that in patients, the left temporal lobe was less specialized in the auditory processing function than in controls.


CONCLUSIONS
In this ADLTLE family, both seizure semiology and neuropsychological findings point to a lateral temporal lobe dysfunction. The newly identified LGI1 mutation might underlie both the seizure disorder and the neuropsychological deficits.
Pisano
Tiziana
T
Department of Child Neurology and Psychiatry, University of Cagliari, Cagliari, Italy.
Marini
Carla
C
Brovedani
Paola
P
Brizzolara
Daniela
D
Pruna
Dario
D
Mei
Davide
D
Moro
Francesca
F
Cianchetti
Carlo
C
Guerrini
Renzo
R
D000328:Adult; D000483:Alleles; D001184:Articulation Disorders / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004007:Dichotic Listening Tests; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000235:genetics*; D005190:Family; D005260:Female; D007839:Functional Laterality / Q000235:genetics* / Q000502:physiology; D005799:Genes, Dominant; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007558:Italy / Q000208:ethnology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins