Absence of mutations in the LGI1 receptor ADAM22 gene in autosomal dominant lateral temporal epilepsy.
Mutations in the LGI1 (leucine-rich, glioma inactivated 1) gene are found in less than a half of the families with autosomal dominant lateral temporal epilepsy (ADLTE), suggesting that ADLTE is a genetically heterogeneous disorder. Recently, it was shown that LGI1 is released by neurons and becomes part of a protein complex at the neuronal postsynaptic density where it is implicated in the regulation of glutamate-AMPA neurotransmission. Within this complex, LGI1 binds selectively to a neuronal specific membrane protein, ADAM22 (a disintegrin and metalloprotease). Since ADAM22 serves as a neuronal receptor for LGI1, the ADAM22 gene was considered a good candidate gene for ADLTE. We have therefore sequenced all coding exons and exon-intron flanking sites in the ADAM22 gene in the probands of 18 ADLTE families negative for LGI1 mutations. Although, we identified several synonymous and non-synonymous polymorphisms, we failed to identify disease-causing mutations, indicating that ADAM22 gene is probably not a major gene for this epilepsy syndrome.
Chabrol
Elodie
E
INSERM U679, Neurology and Experimental Therapeutics, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l'hôpital, 75013 Paris, France.
Gourfinkel-An
Isabelle
I
Scheffer
Ingrid E
IE
Picard
Fabienne
F
Couarch
Philippe
P
Berkovic
Samuel F
SF
McMahon
Jacinta M
JM
Bajaj
Nandita
N
Mota-Vieira
Luisa
L
Mota
Rui
R
Trouillard
Oriane
O
Depienne
Christel
C
Baulac
Michel
M
LeGuern
Eric
E
Baulac
Stéphanie
S
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*
D009419:Nerve Tissue Proteins; D051722:ADAM Proteins; C498474:ADAM22 protein, human