GABRG2Gene Mutation Analysis In The Patient With Complex Febrile Seizure

ObjectiveFebrile seizures (FS, also called Febrile convulsions, FC) are the most commonconvulsive disorders in infancy，which is defined as seizures with fever occurred in earlychildhood, and the exclusion of the central nervous system infections and had no febrileconvulsions in a history. Incidence of between2%to5%, in children，the prognosis isusually good, but about3%of the children can develop to non-febrile convulsions,namely epilepsy. The clinical course of this disease diversity, can be divided into twotypes of simple febrile seizures (simple febrile seizure, SFS) and complex febrileseizures (complex febrile seizure，CFS). In CFS, the age of onset may be less than <6months or more than6years old, the onset temperature can be less than38℃. The onsetform show partial seizures performance, one time or more times recur within24hours,longer convulsion time, some up to20to30minutes. Before the onset, the centralnervous system abnormalities (such as: mental retardation, brain injury or cerebralhypoplasia, etc.) may be present. The heat back a week, EEG still remain abnormalfeature. CFS may be caused by viral infection, abnormal nerve biochemistry and brainpathological changes. Its etiology and pathogenesis is not fully understood, may be theresult of both environmental and genetic factors. The present study suggests that thisdisease can have a significant genetic predisposition, may be autosomal dominantinheritance, recessive inheritance and polygenic inheritance also been reported. Up tonow, with the neurological researches by the familials of different races and regions, thefebrile seizures susceptibility genes loci have been located as:8q13-21(FEB1),19p13.3(FEB2),2q23-24(FEB3), q14-15(FEB4) and6q22-24(FEB5) and so on. In this study,we will use the extraction of human genomic DNA, PCR amplification and DNAsequence analysis to scan all nine exons and adjacent intron regions of CFSpathogenicity-related gene GABRG2in order to obtain exact types of mutations.Preliminary analysis of the relationship between genotype and phenotype of the CFSpatients provide data for CFS molecular etiology studies to help CFS patients withgenetic diagnosis and genetic counseling. MethodsUsing the classic Miller proteinase K-sodium chloride salting out, total genomicDNA was extracted from the peripheral blood leukocytes of2CFS patients and50unrelated healthy controls. Polymerase chain reaction (PCR) amplification all nineexons and the surrounding parts of the introns of GABRG2gene. PCR products aresequenced by direct DNA sequencing with the forward and reverse primers. Refer to theexisting domestic and international studies and reports, the relationship between theCFS genotype and phenotype will be preliminary analyzed.Results1. In this study, patient1was detected a mutation of GABRG2gene, W390X. Hisfather had also been detected the same mutation, but not the incidence. His mother didnot detect the mutation.2. In this study, the second boy was detected GABRG2gene W390X mutation. Hisfather did not detect the mutation, but the mother was detected the same mutation site,his brother not doing this mutant gene screening.3. This study detected gene variants are point mutations.Conclusions1. This study examined GABRG2gene W390X mutation in two cases of CFSchildren, consistent with previously reported hotspot mutation, indicating that W390Xis also the hotspot mutation of two cases of CFS patients.2. W390X mutation showed autosomal dominant inheritance with incompletepenetrance in CFS patients.3. Leading to different clinical phenotypes of the same gene with a point mutationwill be studied further.