[Generalized epilepsy with febrile seizures plus: clinical and genetic analysis of three Serbian families].
The results of clinical and genetic analysis of three Serbian families (pedigrees) with autosomal dominant inheritance, incomplete penetrance and phenotypic features of GEFS+ are presented in this study. Mutation analysis of the SCN1A, SCN1B and GABRG2 genes was performed in all affected and some unaffected members of these three families. Twenty-six exons of SCN1A, five exons of SCN1B and nine exons of GABRG2 were individually amplified using primers based on intronic sequence. PCR products were sequenced in both forward and reverse directions. Subsequently, the samples were run and analyzed using 377 DNA automated sequencer. No consanguinity was noticed. The MM and OM family members live in Republic of Srpska while KS family originates from the central Serbia. No mutations of the exons of SCN1A, SCN1B and GABRG2 genes were found in tested subjects. Obligate carriers in MM family (III-1, III-2, and III-4) exhibit variable expressivity or incomplete penetrance rather than proof of polygenetic inheritance. OM pedigree follows autosomal dominant pattern despite reduced penetrance. Bilinear transmission may assume the possibility of multigenetic mode of inheritance in KS family. The fact that all affected members in three Serbian families were negative for mutations in SCN1A, SCN1B and GABRG2 genes strongly supports the hypothesis of significant genetic heterogeneity of GEFS+. Recognizing GEFS+ on clinical grounds contributes to more precise integration of this syndrome into already existing classification of epileptic syndromes.
Ristić
Aleksandar J
AJ
Institute of Neurology, Clinical Centre of Serbia, Belgrade.
Janković
Slavko
S
Annesi
Grazzia
G
Carrideo
Sara
S
Annesi
Ferdinanda
F
Gambardella
Antonio
A
Maksimović
Goran
G
Gnjatović
Brankica
B
Petrović
Igor
I
Vojvodić
Nikola
N
Sokić
Dragoslav
D
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D003294:Seizures, Febrile / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D015022:Yugoslavia