Screening of SCN1A gene mutation in 10 families with generalized epilepsy accompanied by febrile seizure / 解放军医学杂志

Objective To analyze the phenotypes and to identify SCN1A gene mutation in families with generalized epilepsy accompanied by febrile seizures (GEFS+). Methods The clinical data were collected, and genomic DNA was extracted from peripheral blood lymphocytes of the proband and available members in the GEFS+ families. The phenotypes of the related members were analyzed. The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing. Results Thirty-three related members from 10 GEFS+ families, ranged from 2 to 7 members in each family received the examination. T heir phenotypes included febrile seizures (FS) in 11 persons (33.3%), febrile seizures plus (Fs+) in 11 (33.3%), FS with partial seizures in 1 (3.0%), afebrile generalized tonic-clonic seizures (AGTCS) in 3 (9.1%), Dravet syndrome in 1 (3.0%), childhood absence epilepsy in 1 (3.0%), and unclassified seizures in 5 members (15.2%). SCN1A mutations were found in 3 families, including one family with missense mutation (glu1444-lys), and silent mutation: synonymous mutation existed in exon 15 (c.2592G>A), with synonymous mutation in exon 9 (c.1212 G>A) and exon 26 (c.5385 G>A) in two families. Conclusions A new missense mutation and three synonymous mutation have been found in the coding regions of SCN1A gene in three families. One of the families has synonymous mutation in two exons. Genetic mechanism is complicated in GEFS families.

Brain-derived Neurotrophic Factor(BDNF) SNP 6265 Polymorphisms in Febrile Seizure and GEFS+

PURPOSE: Febrile seizure(FS) is one of the most common neurological conditions during childhood, but the pathogenesis of FS remains ambiguous. Various studies have shown that brain-derived neurotrophic factor(BDNF) increased neuronal excitability. In this study, to determine whether the polymorphisms of SNP 6265 within the gene encoding BDNF are associated with susceptibility to FS, the frequencies of the polymorphisms were investigated in children with FS and control subjects. In addition, we analyzed the SNP 6265 polymorphisms in Generalized epilepsy with febrile seizures plus (GEFS+) that hasn't been studied as yet in Korea. METHODS: A total of 79 children selected throughout a collaborative study of Catholic Child Neurology Research Group were divided into three groups: (1) FS(n=30); (2) GEFS+ (n=19); (3) control subjects(n=30). Genotypes and allelic frequencies for the polymorphisms of SNP 6265 located at nucleotide 196 was analyzed and compared among the groups. RESULTS: In this study, proportions for A homozygote, A/G heterozygote and G homozygote for BDNF were as follows: in FS, 46.7%, 36.7% and 16.7%, in GEFS+, 26.3%, 47.4% and 26.3% and in control subjects, 60.0%, 16.7% and 23.3%. The allele A and G frequencies for BDNF in FS were 65.0% and 35.0%, in GEFS+ were 50% and 50%, and in control subjects were 68.3% and 31.7%. However, these differences in genotype proportions and allele frequencies among three groups were not significant. CONCLUSION: These results suggest that genomic variations of BDNF might not be the susceptibility factor for FS and GEFS+ in Korean population.

Clinical Analysis and Gene Mutation Screening of Voltage-Gated Sodium Channel ?1 Subunit in 2 Generalized Epilepsy with Febrile Seizures Plus Families / 实用儿科临床杂志

Objective To explore the mutation of voltage-gated sodium channel ?1 subunit(SCN1B)gene in Chinese Han families with generalized epilepsy with febrile seizures plus(GEFS+).Methods Two families pedigrees were established and disease history,physical examination were collected in order to analyze the mode of inheritance.The mutation sites of reported SCN1B gene exon 3-(C46T,G47A,C156G)were detected by polymerase chain reaction sequence special primers(PCR-SSP)method after genomic DNA were extracted.Results There were 13 patients in the 2 families,all were Han people and 9 cases were living.The results showed the mode of inheritance basically corresponds with autosomal dominant inheritance complicated with incomplete penetrance,and leaded to different kinds of phenotype.The mutation sites of SCN1B gene exon 3 were detected by using PCR-SSP method,and heterozygote was not found,and point mutations were also not found in the 2 families.Conclusions GEFS+ is a complex disorder with genetic heterogeneity.There were no gene mutations of SCNIB in the 2 GEFS+ families,which might suggets the possibility of insufficient samples as the patients came from Henan province and the possibility of differences from races and regions of other countries.

Analysis of Gene Mutation of Voltaged-Gated Sodium Channel ?1 Subunit in 2 Generalized Epilepsy with Febrile Seizures Plus Families / 实用儿科临床杂志

Objective To collect the families with generalized epilepsy with febrile seizures plus(GEFS+) and analyze the clinical status and heredity features of Chinese GEFS+.Voltaged-gated sodium channel ?1 subunit(SCN1B) gene of 2 families were detected,and expect to find new mutation sites.Methods All participant in the study of 2 families members were informed of voluntary participate in this investigation,health examination and blood sampling.All 6 gene exons of proband,patients and healthy control group were sequenced.The sequencing result was compared and analyzed with the normal sequence of genomic exon fragment and exon fragment sequencing result of control group through internet(BLAST).Results 1.A new G/A heterozygous polymorphism (G181A)was found in the 181th basyl of SCN1B gene exon 3,and codon was changed from TCG to TCA,both encoding serine (Ser,S).It was synonymous mutation.2.A new G/A heterozygous polymophism(G15A)was found in the 15th basyl of SCN1B gene exon 3,and codon was changed from GAG to GAA,both encoding glutamic acid(Glu,E).It belonged to synonymous mutation.3.A new T/C heterozygous polymorphism (T37C)was found in the 37th basyl of SCN1B gene exon 6.The patients genetype were:5 cases with T/C heterozygote,3 cases with T/T homozygote,2 cases with C/C homozygote.Healthy control group were all T/T homozygote.Allele frequency distribution for T was 55.0%,and 45.0% for C.4.A new A/C heterozygous polymorphism (A81C)was found in the 81th basyl of SCN1B gene exon 6.The patients genetype were:5 cases with A/C heterozygote,3 cases with A/A homozygote,2 cases with C/C homozygote.Healthy control group were all A/A homozygote.Allele frequency distribution for A was 55.0%,and 45.0% for C.Conclusions Two new heterozygous polymorphism (G181A),(G15A) were found in SCN1B gene exon 3.Two new heterozygous polymorphism (T37C),(A81C) were found in SCN1B gene exon 6.These 4 polymorphism enriched single nucleotide polymorphism(SPN) database and provided candidate sites for the research of epilepsy susceptbility polymorphisms.

Gene related to generalized epilepsy with febrile seizures plus / 医学研究生学报

Generalized epilepsy with febrile seizures plus is a novel and common generalized epilepsy syndromes, with significant genetic and phenotypic heterogeneity. Research on genetic position and mutant of generalized epilepsy with febrile seizures plus has been a hot spot, which has importance in clarifying epilepsy syndrome as a kind of channelopathy.

Study Progress of Voltaged-Gated Sodium Channel Gene in Generalized Epilepsy with Febrile Seizures Plus / 实用儿科临床杂志

Generalized epilepsy with febrile seizures plus(GEFS+) is a new epilepsy syndrome proposed by International League Against Epilepsy.At present,the progress of genetic studies of GEFS+ focus on gene mapping based on family analysis,many researches indicate that GEFS+ is associated with voltaged-gated sodium channel(SCN) gene mutation.This paper intends to discuss the relationship beween GEFS+ and SCN1B,SCN2B,SCN1A,SCN2A genes,mutations in order to improve the cognition about GEFS+.