Analysis of LGI1 promoter sequence, PDYN and GABBR1 polymorphisms in sporadic and familial lateral temporal lobe epilepsy.
Autosomal dominant lateral temporal epilepsy (ADTLE) is a genetically transmitted epileptic syndrome characterized by focal seizures with predominant auditory symptoms likely originating from the lateral region of the temporal lobe. Mutations in coding region or exon splice sites of the leucine-rich, glioma-inactivated 1 (LGI1) gene account for about 50% of ADLTE families. De novo LGI1 mutations of the same kind have also been found in about 2.5% of non-familial cases with idiopathic partial epilepsy with auditory features (IPEAF). In both conditions, mutations in the LGI1 promoter region have not been reported. We sequenced the minimal promoter region of LGI1 in the probands of 16 ADLTE families and in 104 sporadic IPEAF patients and no mutations clearly linked to the disease were found. However, two polymorphisms, -500G>A and -507G>A, with potential functional implications were identified and analysed in the cohort of sporadic IPEAF patients but their frequencies did not differ from those found in a control population of similar age, gender and geographic origin. We also analysed in our study population the GABA(B) receptor 1 c.1465G>A and the prodynorphin promoter 68-bp repeat polymorphisms, previously associated with temporal lobe epilepsy. None of these polymorphisms showed a significant association with IPEAF, whereas a tendency towards association with the prodynorphin low expression (L) alleles was found in the small group of ADLTE index cases, in agreement with previous studies suggesting that this polymorphism is a susceptibility factor in familial forms of temporal lobe epilepsy.
Bovo
Giorgia
G
CNR-Institute of Neurosciences, Section of Padua, Padova, Italy.
Diani
Erica
E
Bisulli
Francesca
F
Di Bonaventura
Carlo
C
Striano
Pasquale
P
Gambardella
Antonio
A
Ferlazzo
Edoardo
E
Egeo
Gabriella
G
Mecarelli
Oriano
O
Elia
Maurizio
M
Bianchi
Amedeo
A
Bortoluzzi
Stefania
S
Vettori
Andrea
A
Aguglia
Umberto
U
Binelli
Simona
S
De Falco
Arturo
A
Coppola
Giangennaro
G
Gobbi
Giuseppe
G
Sofia
Vito
V
Striano
Salvatore
S
Tinuper
Paolo
P
Giallonardo
Anna T
AT
Michelucci
Roberto
R
Nobile
Carlo
C
D001483:Base Sequence; D004745:Enkephalins / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D018080:Receptors, GABA-B / Q000235:genetics*
D004745:Enkephalins; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011498:Protein Precursors; D011506:Proteins; D018080:Receptors, GABA-B; C033660:preproenkephalin