Clinical Analysis And Gene Mutation Screening Of SCN1A With Two Hereditary Epileptic Syndromes (GEFS~+ & Dravet Syndrome)

PART 1 Clinical analysis of GEFS~+ & Dravet SyndromeObjective To study the phenotypes of two diseases,we examined the phenotypic variation and clinical characteristics in two families with generalized epilepsies with febrile seizures plus(GEFS~+) and Dravet syndrome patients.Methods Cases were collected through out-patient clinic and.The information of probands and familial members were obtained by asking history,physical examnition and EEG recording.All cases were diagnosed according to the clinical diagnostic criteria.Results(1) There were 28 affected individuals in two families of GEFS~+ (14males and 14females).Febrile seizures(FS) presented in 7 cases, febrile seizures plus(FS~+) in 6 cases,FS~+ and absence seizures in 1 case, FS~+ and myoclinic seizures in 1 case,uncertain type in 13 cases.No severe phenotype.Bilineal inheritance occurs in one GEFS~+ family.(2) The common manifestations of three Dravet syndrome cases were: onset during the first year of life;in all patients the seizures were associated with febrile illness and changed to afebrile seizures after lyear;the form of seizures contains clonic,myoclonic and atypical absence;the seizures were difficult to control with AEDs;all patients presented some degree of mental delay;there were sharp-slow waves, spike-slow waves and multi spike-slow waves in EEG. Conclusions(1) GEFS~+ is a syndrome with the character of heterogeneous clinical phenotypes:GEFS~+ is autosomal dominant inheritance disease with phenotypic heterogeneity.Bilineal inheritance rases the possibility of complex inheritance with additive gene effects.(2) Dravet syndrome is one of the fever-related epileptiform syndromes,it belongs to encephalopathy with a bad result.The apprehension of GEFS~+ and Dravet syndrome plays an important role in diagnosis and differential diagnosis of epilepsy in childhood.PART 2 Gene Mutation Screening of SCN1AObjective To Find the mutations of SCNIA through gene screening.Methods The DNA of probands was extracted from anticoagulated peripheral blood by using RelaxGene Blood DNA System.The primer was designed for all exons of SCN1A and amplificated all the exons by polymerase chain reaction,the abnormal fragments were discovered through Denaturing high performance liquid chromatography(DHPLC).Direct sequenceing for the abnormal fragments to find the mutation.Results(1) A samesense mutation(c.1212A＞G) of SCN1A gene was found in the proband and an unaffected individual of pedigree B of GEFS~+,it is a SNP. And no mutations was found in the other exons of SCN1A.(2) We found a novel missense mutation of SCN1A gene(c.2867T＞G,M956R) in the Dravet Syndrome patient.Conclusions(1) Only one SNP but no pathogenic mutation was foud in SCNIA gene in the proband of pedigree B of GEFS~+,consistent with the heterogeneity prevalent in this disorder.(2) The finding of a novel missense mutation of SCN1A in Dravet syndrome patient supports the relationship of SCN1A gene mutation and the disease.