| The name of generalized epilepsy with febrile seizures plus(GEFS+) has been used for more than ten years and was listed as "syndromes in development" by the 2001 ILAE Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy. With the development of molecular genetics,Scheffer recently proposed changing the name of GEFS+ to "genetic epilepsy with febrile seizures plus" from "generalized epilepsy with febrile seizures plus".This was because although generalized epilepsies predominate in GEFS+ families,focal or partial epilepsies are well recognized with and without preceding FS.The problematic name was changed,but the uncertain relationship between the phenotype and the genotype still puzzles the researchers.Objective We mapped the genes of three GEFS+ families from the north of China, calculate mutation rate of GeEFS+,and analyze the relationship between the phenotype and the genotype of GEFS+ in order to explore the possible molecular mechanisms of GeEFS+ and the feasible study methods。We emphasize that further study on molecular genetic mechanisms is very important to epilepsy etiology,classification of epilepsy syndromes and clinical practice.Methods In the first part,we used allele sharing and linkage analysis to genotype the family members in Family Tian and Family Chai with microsatellites for reported 5 candidate genes and 4 candidate loci for GEFS+ and FS.We screened all STRs according to the evaluation criterion of LOD score(≥2:hint of linkage atθ=0;≤-2:hint of no linkage atθ=0).The Cylliric2.0 software was used to reconstruct haplotype for fine mapping.Then,a mutation search by means of direct sequencing was performed in the coding exons,flanking splice sites and promotor of two genes(GABRG2 and GABRA1). Only allele sharing was performed to screen 5 candidate genes in Family Di.In the second part,first,the literatures retrieval was performed at Pubmed and Wanfang database.The articles on FS,GEFS+,PEFS+ and familial TLE with febrile seizures were included.Second,the information on characteristics of mutations in three genes(SCN1B, SCN1A and GABRG2) was collected.Third,mutation rate of SCN1B,SCN1A, GABRG2,SCN2A and GABRD in GeEFS+ was calculated.Fourth,the phenotypes among the families with mutations in three genes(SCN1B,SCN1A and GABRG2) and between the families with and without mutations were compared.Results Family Tian had a maximum LOD score(Zmax=2.043) atθ=0 for D5S422.In this family,linkage to 6Mb region between D5S820 and D5S422 could be possible based on haplotype analysis.Direct sequencing in GABRG2 and GABRA1 was performed,and no causal mutations were found.Six SNPs were detected,including rs11135176 and rs211037 in GABRG2 and rs11575999,rs41275339,rs11576004 and rs2279020 in GABRA1.Co-segregation of rs11575999,rs41275339 and rs11576004 with phenotype was excluded and association on rs211037 with phenotype was not found.Linkage to all candidate genes and loci could be excluded in Family Chai and Di.The families with mutation in SCN1A had more specific characters in phenotype: FS+ much more than FS,wide phenotype distribution,higher penetrance,early onset and rare single FS.Location and type of the mutations as well as effect of the mutations on ion Channel were associated with phenotype.In the families with mutation in GABRG2, the patients with FS were more than those with FS+,partial seizures were rare,and the mutations in benzodiazepin binding pocket were associated with absence seizures.In the families with mutations in SCN1B,the patients with FS and FS+ were similar to those with mutations in SCN1A,but the quantity of phenotype was not as much as the latter. FS was more oftern than FS+ in the families in which mutations could not be found. Although the quantity of phenotype was much,severe phenotype was not found,such as MAE and SMEI..Conclusion Although it is very difficult to find the causal mutations in most of the Autosome dominant FS families and GEFS+ with simple phenotype and without severe phenotype,further study on molecular genetics in GeEFS is by no means nonsignificant, which could facilitate study on molecular mechanisms of epilepsies with severe phenotype or refractory epilepsies.We supplemented the candidate genes and loci, optimized the genetic markers,performed direct senquencing in promoters, co-segregation analysis in three SNPs besides sequencing in the coding exons and family-based association tests in one SNP,which established a substantial foundation for further gene localization. Research on health-related quality of life(HRQOL) in adolescents with epilepsy began relatively late in China,even though significant advances had been made in Western societies.One reason for this was the unavailability of valid measures for measuring and evaluating adolescents' HRQOL in China.The Quality of Life in Epilepsy Inventory for Adolescents(QOLIE-AD-48) is the most frequently recommended questionnaire for measuring HRQOL in youths with epilepsy and has been used in different studies to date.The QOLIE-AD 48 has been validated in several languages,including Spanish,Serbian,and Brazilian Portuguese recently,and these translations have been shown to be as specific and sensitive as the original version.Objective The aim of this study was to translate into Chinese the Quality of Life in Epilepsy Inventory for Adolescents(QOLIE-AD-48) and to evaluate its psychometric properties.Methods The QOLIE-AD-48 was translated according to the procedure of the European Organization for Research and Treatment of Cancer(EORTC) Quality of Life Group. After a multistage translation and cultural adaptation,the final Chinese version was administered to 145 adolescents with epilepsy to evaluate its validity and reliability.The inclusion criteria were:(1) active epilepsy(i.e.,at least one seizure in the last 2 years); (2) epilepsy duration longer than 2 years;(3) no change in antiepileptic drug regimens in the past 4 months;(4) regular school attendance with ability to read and write Chinese.Adolescents who had had brain surgery,used a concomitant medication with central nervous system effects,or had progressive neurological or psychiatric illness were not considered eligible for the study.Test-retest analysis was administered to 45 adolescents without significant changes in health and social status during a two-four weeks' interval between test and retest.Interitem correlations,correlations with the Pediatric Quality of Life Inventory(PedsQL),internal consistency,test-retest reliability and sensitivity were examined.Results The main translational problems encountered in developing the Chinese QOLIE-AD-48 were due to discrepancies in verbs form and exact meanings,which involved mainly the content of some items.Cross-cultural problems were also difficult to he solved.The acceptability,as well as the feasibility,of the Chinese version appeared satisfactory,considering that 75.9%of the adolescents completed the entire instrument within 10-25 min.Mean total score was 67.5,and all subscales contributed significantly to the summary measure.Considering the validity of the translation,each item correlated Research on health-related quality of life(HRQOL) in adolescents with epilepsy began relatively late in China,even though significant advances had been made in Western societies.One reason for this was the unavailability of valid measures for measuring and evaluating adolescents' HRQOL in China.The Quality of Life in Epilepsy Inventory for Adolescents(QOLIE-AD-48) is the most frequently recommended questionnaire for measuring HRQOL in youths with epilepsy and has been used in different studies to date.The QOLIE-AD 48 has been validated in several languages,including Spanish,Serbian,and Brazilian Portuguese recently,and these translations have been shown to be as specific and sensitive as the original version.Objective The aim of this study was to translate into Chinese the Quality of Life in Epilepsy Inventory for Adolescents(QOLIE-AD-48) and to evaluate its psychometric properties.Methods The QOLIE-AD-48 was translated according to the procedure of the European Organization for Research and Treatment of Cancer(EORTC) Quality of Life Group. After a multistage translation and cultural adaptation,the final Chinese version was administered to 145 adolescents with epilepsy to evaluate its validity and reliability.The inclusion criteria were:(1) active epilepsy(i.e.,at least one seizure in the last 2 years); (2) epilepsy duration longer than 2 years;(3) no change in antiepileptic drug regimens in the past 4 months;(4) regular school attendance with ability to read and write Chinese.Adolescents who had had brain surgery,used a concomitant medication with central nervous system effects,or had progressive neurological or psychiatric illness were not considered eligible for the study.Test-retest analysis was administered to 45 adolescents without significant changes in health and social status during a two-four weeks' interval between test and retest.Interitem correlations,correlations with the Pediatric Quality of Life Inventory(PedsQL),internal consistency,test-retest reliability and sensitivity were examined.Results The main translational problems encountered in developing the Chinese QOLIE-AD-48 were due to discrepancies in verbs form and exact meanings,which involved mainly the content of some items.Cross-cultural problems were also difficult to he solved.The acceptability,as well as the feasibility,of the Chinese version appeared satisfactory,considering that 75.9%of the adolescents completed the entire instrument within 10-25 min.Mean total score was 67.5,and all subscales contributed significantly to the summary measure.Considering the validity of the translation,each item correlated... |
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