Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.
Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.
Morante-Redolat
José M
JM
Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, Jaume Roig 11, E-46010 València, Spain.
Gorostidi-Pagola
Ana
A
Piquer-Sirerol
Salomé
S
Sáenz
Amets
A
Poza
Juan J
JJ
Galán
Juan
J
Gesk
Stefan
S
Sarafidou
Theologia
T
Mautner
Victor-F
VF
Binelli
Simona
S
Staub
Eike
E
Hinzmann
Bernd
B
French
Lisa
L
Prud'homme
Jean-F
JF
Passarelli
Daniela
D
Scannapieco
Paolo
P
Tassinari
Carlo A
CA
Avanzini
Giuliano
G
Martí-Massó
José F
JF
Kluwe
Lan
L
Deloukas
Panagiotis
P
Moschonas
Nicholas K
NK
Michelucci
Roberto
R
Siebert
Reiner
R
Nobile
Carlo
C
Pérez-Tur
Jordi
J
López de Munain
Adolfo
A
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D011817:Rabbits; D020449:Repetitive Sequences, Amino Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins