Spectrum in Seven Italian Families Unrelated to SCN1A, SCN1B, and GABRG2 Gene Mutations

Summary: Purpose: We describe seven Italian families withgeneralized epilepsy with febrile seizures plus (GEFS + ), inwhich mutations of SCN1A, SCN1B, and GABRG2 genes wereexcluded and compare their clinical spectrum with that of pre-viously reported GEFS + with known mutations. Methods: We performed a clinical study of seven families(167individuals).Themolecularstudyincludedanalysisofpoly-merase chain reaction (PCR) fragments of SCN1A and SCN1B exons by denaturing high-performance liquid chromatography(DHPLC) and direct sequencing of GABRG2 in all families.We excluded SCN1A, SCN1B , and GABRG2 genes with linkageanalysis in a large pedigree and directly sequenced SCN2A ina family with neonatal–infantile seizures onset. We comparedthe epilepsy phenotypes observed in our families with those ofGEFS + families harboring mutations of SCN1A, SCN1B , and GABRG2 and estimated the percentage of mutations of thesegenes among GEFS + cases by reviewing all published studies. Results : Inheritance was autosomal dominant with 69% pen-etrance. Forty-one individuals had epilepsy: 29 had a pheno-type consistent with GEFS