title: No evidence of GABRG2 mutations in severe myoclonic epilepsy of infancy.
abstract: 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
authors.affiliation: Laboratory of Human Genetics, E O Ospedali Galliera, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cecconi
authors.forename: Daniela
authors.initials: D
authors.lastname: Buti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Capovilla
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dalla Bernardina
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Annarita
authors.initials: A
authors.lastname: Ferrari
authors.forename: Elena
authors.initials: E
authors.lastname: Fontana
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaggero
authors.forename: Melania
authors.initials: M
authors.lastname: Giannotta
authors.forename: Lucio
authors.initials: L
authors.lastname: Giordano
authors.forename: Tiziana
authors.initials: T
authors.lastname: Granata
authors.forename: Lorita
authors.initials: L
authors.lastname: La Selva
authors.forename: Maria
authors.initials: M
authors.lastname: Luisa Lispi
authors.forename: Margherita
authors.initials: M
authors.lastname: Santucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Vanadia
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Piernanda
authors.initials: P
authors.lastname: Vigliano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viri
authors.forename: Franca
authors.initials: F
authors.lastname: Dagna Bricarelli
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: 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
chemical_list: C546279:GABRG2 protein, human; D011963:Receptors, GABA-A