No evidence of GABRG2 mutations in severe myoclonic epilepsy of infancy.
Severe myoclonic epilepsy of infancy (SMEI) has been long suspected to have a genetic origin. Recently mutations in the gene encoding a voltage-gated alpha-1 sodium channel subunit-SCN1A-have been identified as a common cause of SMEI. Moreover, a mutation in the gene encoding the gamma2 subunit of the GABA(A) receptor-GABRG2-has been described in a GEFS+ family with a member affected by SMEI. In order to further investigate the role of GABRG2 in the pathogenesis of SMEI, we have screened for mutations 53 SMEI patients who resulted negative for SCN1A mutations. Mutational screening of GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram. Twenty-nine variant chromatograms were identified corresponding to seven different nucleotide variants. None of them leads to an amino acid change or obvious protein dysfunction. No difference in allele frequency was observed for the SMEI patients compared to a control population indicating that these variants are not involved in SMEI. Our study demonstrates that GABRG2 is not a commonly involved in the etiology of SMEI and suggests that other and yet unidentified genes are involved in the syndrome
Madia
Francesca
F
Laboratory of Human Genetics, E O Ospedali Galliera, Genova, Italy.
Gennaro
Elena
E
Cecconi
Massimiliano
M
Buti
Daniela
D
Capovilla
Giuseppe
G
Dalla Bernardina
Bernardo
B
Elia
Maurizio
M
Ferrari
Annarita
A
Fontana
Elena
E
Gaggero
Roberto
R
Giannotta
Melania
M
Giordano
Lucio
L
Granata
Tiziana
T
La Selva
Lorita
L
Luisa Lispi
Maria
M
Santucci
Margherita
M
Vanadia
Francesca
F
Veggiotti
Pierangelo
P
Vigliano
Piernanda
P
Viri
Maurizio
M
Dagna Bricarelli
Franca
F
Bianchi
Amedeo
A
Zara
Federico
F
D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D012720:Severity of Illness Index
C546279:GABRG2 protein, human; D011963:Receptors, GABA-A