上海市崇明县热性惊厥与SCN1A基因热点多态性变异的相关性分析
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摘要
目的·了解上海市崇明县儿童热性惊厥(FS)与电压门控钠离子通道α1亚型(SCNIA)基因外显子25、26及3'UTR区域之间的相关性。方法·提取96例FS患儿[包括32例全面性癫痫伴热性惊厥附加症(GEFS+)患儿]和53例健康对照组儿童的外周静脉血基因组DNA,进行SCNIA基因E25、E26及3'UTR区域PCR扩增及测序分析。结果·病例组和对照组SCNIA基因E25、E26均未见突变。3'UTR区域1例GEFS+患儿存在c.310-311delGT变异,2例FS患儿存在c.589T>G变异,6例存在c.593T>G变异;对照组均未发现变异。病例组和对照组已报道的单核苷酸多态性(SNP)c.1025T>C发生频率分别为18.2%和24.5%,2组间差异无统计学意义。预测结果显示114种miRNA能与SCNIA基因3'UTR区结合。c.310-311delGT不位于miRNA与SCN1A基因3'UTR区的结合序列内,c.589T>G变异、c.589T>G变异均位于此序列中。结论·经检测SCNIA基因E25、E26均未见突变;3'UTR区域发现c.310-311de1GT、c.589T>G和c.593T>G变异;SNPc.1025T>C与FS无明显关联。
Objective · To explore the correlation of febrile seizure(FS) with voltage-gated sodium channel alpha 1 subtype(SCNIA) gene exons 25,26 and3'UTR region in children from Shanghai chongming County.Methods · The genomic DNA in peripheral venous blood was extracted from 96 children with FS(including 32 cases of genetic epilepsy with febrile seizures plus[GEFS+]) and 53 healthy controls.PCR amplification and sequencing analysis were performed for SCNIA gene exons 25,26 and 3'UTR region.Results · No mutation in SCN1 A gene exons E25,E26 was found in both groups.For 3'UTR region,c.310-311 delgt GT variation was found in 1 case of GEFS+,c.589 T> G variation in 2 cases of FS,and c.593 T>G variation in 6 cases,while no mutation was found in the control group.Reported frequencies of single nucleotide polymorphism(SNP) c.l025T>C were 18.2%(the case group) and 24.5%(the control group).The difference between two groups was not statistically significant.Prediction results showed that 114 microRNAs could bind with the 3'UTR region of SCNIA gene.C.310-311 delGT was not located in the sequence where miRNAs bound with 3'UTR region of SCNIA gene,while c.589 T>G and c.593 T > G variations were located in this sequence.Conclusion · No mutation was found in SCNlAgene exons E25,E26.The c.310-31 IdelGT,c.589 T > G,and c.593 T > G variations were found in 3'UTR region.There is no obvious correlation between SNPc.l025T>C and FS.
Objective · To explore the correlation of febrile seizure(FS) with voltage-gated sodium channel alpha 1 subtype(SCNIA) gene exons 25,26 and3'UTR region in children from Shanghai chongming County.Methods · The genomic DNA in peripheral venous blood was extracted from 96 children with FS(including 32 cases of genetic epilepsy with febrile seizures plus[GEFS+]) and 53 healthy controls.PCR amplification and sequencing analysis were performed for SCNIA gene exons 25,26 and 3'UTR region.Results · No mutation in SCN1 A gene exons E25,E26 was found in both groups.For 3'UTR region,c.310-311 delgt GT variation was found in 1 case of GEFS+,c.589 T> G variation in 2 cases of FS,and c.593 T>G variation in 6 cases,while no mutation was found in the control group.Reported frequencies of single nucleotide polymorphism(SNP) c.l025T>C were 18.2%(the case group) and 24.5%(the control group).The difference between two groups was not statistically significant.Prediction results showed that 114 microRNAs could bind with the 3'UTR region of SCNIA gene.C.310-311 delGT was not located in the sequence where miRNAs bound with 3'UTR region of SCNIA gene,while c.589 T>G and c.593 T > G variations were located in this sequence.Conclusion · No mutation was found in SCNlAgene exons E25,E26.The c.310-31 IdelGT,c.589 T > G,and c.593 T > G variations were found in 3'UTR region.There is no obvious correlation between SNPc.l025T>C and FS.
引文
[1]张立凤.热性惊厥研究进展[J].医学理论与实践,2013,26(13):1711-1712.
[2]Scheffer IE,Berkovic SF.Generalized epilepsy with febrile seizures plus:a genetic disorder with heterogeneous clinical phenotypes[J].Brain,1997,120:479-490.
[3)Nakayama J.Progress in searching for the febrile seizure susceptibility genes[J].Brain Dev,2009,31(5):359-365.
[4]Cui X,Zeng F,Liu Y,et al.A novel SCNIA missense mutation causes generalized epilepsy with febrile seizures plus in a Chinese family[J].Neurosci Lett,2011,503(1):27-30.
[5]钟建民.热性惊厥的临床诊治策略[J].实用儿科临床杂志,2012,27(24):1856-1859.
[6]徐美春,王秀敏,水泉祥热性惊厥相关基因突变研究进展[J].中国妇幼健康研究,2006,5(3):412—414.
[7]郭嘉诚.SCNlA基因变化在家族性热性惊厥发病中的作用[D].蚌埠:蚌埠医学院,2014.
[8]Malacame M,Madia F,Gennaro E,et al.Lack of SCNIA Mutations in familial febrile seizures[J].Epilepsia,2002,43(5):559-562.
[9]李建华,王家勤,郭学鹏,等.全面性癫痫伴热性惊厥附加症电压门控钠离子通道基因的研究进展[J].实用儿科临床杂志,2010,25(5):368—370.
[10]陈志红,翟琼香,丁健,等.全面性癫痫伴热性惊厥附加症家系SCNlA及G ABRG2基因突变筛查[J].实用儿科临床杂志,2011,26(12):911-914.
[11]张丽敏,康熙雄,张国军.钠离子通道基因SCN1A、SCN2A、SCN1B突变与癫痫[J].中国医药生物技术,2013,8(1):62—65.
[12]Dimova PS,Yordanova I,Bojinova V,et al.Generalized epilepsy with febrile seizures plus:novel SCNIA mutation[J].Pediatr Neurol,2010,42(2):137-140.
[13]Fendri-Kriaa N,Kammoun F,Rebai A,et al.Genetic screening of two Tunisian families with generalized epilepsy with febrile seizures plus[J].Eur Neurol,2009,16(6):697-704.
[14]Herini ES,Gunadi,Harahap IS,et al.Generalized epilepsy with febrile seizures plus(GEFS+)spectrum:clinical manifestations and SCN1A mutations in Indonesian pattents[J].Epilepsy Res,2010,90(1-2):132-139.
[15]Volkers L,Kahlig KM,Verbeek NE,et al.Navl,Idysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome[J].Neurosci,2011,34(8):1268-1275.
[16]Polizzi A,Incorpora G,Pavone P,et al.Generalised epilepsy with febrile seizures plus(GEFS+):molecular analysis in a restricted area[J].Childs Nerv Syst,2012,28(1):141-145.
[17]LossinC.Acatalog of SCN1A varian[J].Brain Dev,2009,31(2):114-130.
[18]Nagao Y,Mazaki ME,Okamura N,et al.A family of generalized epilepsy with febrile seizures plus type2-a new missense mutation of SCN1A found in the pedigree of several patients with complex febrile seizures[J].Epilepsy Res,2005,63(2-3):151-156.
[19]Gambardella A,Marini C.Clinical spectrum of SCN1A mutation[J].Epilepsia,2009,50(suppl5):20-23.
[20]于美娟,陈俐,高玫梅,等.具有SCN1A基因错义突变(R1596C)的遗传性GEFS+家系1例报道[J].现代医院,2009,9(12):3-5.
[21]王海霞,王莹.刘定干.真核生物mRNA3]非翻译区的功能[J].生物化学与生物物理进展,2008,35(9):980—985.
[22]Zeng T,Dong ZF,Liu SJ,et al.A novel variant in the 3'UTR of human SCNIA gene from a patient with Dravet syndrome decreases mRNA stability mediated by GAPDH's binding[J].Hum Genet,2014,(133):801-811.
[23]冯超,唐宁,方绍海.等.法洛四联症患儿NOTCH2基因3'UTR区域突变分析[J].上海交通大学学报(医学版).2015,35(4):476-482.
[24]Zhang HS,Wu QY,Xu M.Mitogen-activated protein kinase signal pathways play an important rule in right ventricular hypertrophy of tetralogy of Fallot[J].Chin Med,2012,125(13):2243-2249.
[2]Scheffer IE,Berkovic SF.Generalized epilepsy with febrile seizures plus:a genetic disorder with heterogeneous clinical phenotypes[J].Brain,1997,120:479-490.
[3)Nakayama J.Progress in searching for the febrile seizure susceptibility genes[J].Brain Dev,2009,31(5):359-365.
[4]Cui X,Zeng F,Liu Y,et al.A novel SCNIA missense mutation causes generalized epilepsy with febrile seizures plus in a Chinese family[J].Neurosci Lett,2011,503(1):27-30.
[5]钟建民.热性惊厥的临床诊治策略[J].实用儿科临床杂志,2012,27(24):1856-1859.
[6]徐美春,王秀敏,水泉祥热性惊厥相关基因突变研究进展[J].中国妇幼健康研究,2006,5(3):412—414.
[7]郭嘉诚.SCNlA基因变化在家族性热性惊厥发病中的作用[D].蚌埠:蚌埠医学院,2014.
[8]Malacame M,Madia F,Gennaro E,et al.Lack of SCNIA Mutations in familial febrile seizures[J].Epilepsia,2002,43(5):559-562.
[9]李建华,王家勤,郭学鹏,等.全面性癫痫伴热性惊厥附加症电压门控钠离子通道基因的研究进展[J].实用儿科临床杂志,2010,25(5):368—370.
[10]陈志红,翟琼香,丁健,等.全面性癫痫伴热性惊厥附加症家系SCNlA及G ABRG2基因突变筛查[J].实用儿科临床杂志,2011,26(12):911-914.
[11]张丽敏,康熙雄,张国军.钠离子通道基因SCN1A、SCN2A、SCN1B突变与癫痫[J].中国医药生物技术,2013,8(1):62—65.
[12]Dimova PS,Yordanova I,Bojinova V,et al.Generalized epilepsy with febrile seizures plus:novel SCNIA mutation[J].Pediatr Neurol,2010,42(2):137-140.
[13]Fendri-Kriaa N,Kammoun F,Rebai A,et al.Genetic screening of two Tunisian families with generalized epilepsy with febrile seizures plus[J].Eur Neurol,2009,16(6):697-704.
[14]Herini ES,Gunadi,Harahap IS,et al.Generalized epilepsy with febrile seizures plus(GEFS+)spectrum:clinical manifestations and SCN1A mutations in Indonesian pattents[J].Epilepsy Res,2010,90(1-2):132-139.
[15]Volkers L,Kahlig KM,Verbeek NE,et al.Navl,Idysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome[J].Neurosci,2011,34(8):1268-1275.
[16]Polizzi A,Incorpora G,Pavone P,et al.Generalised epilepsy with febrile seizures plus(GEFS+):molecular analysis in a restricted area[J].Childs Nerv Syst,2012,28(1):141-145.
[17]LossinC.Acatalog of SCN1A varian[J].Brain Dev,2009,31(2):114-130.
[18]Nagao Y,Mazaki ME,Okamura N,et al.A family of generalized epilepsy with febrile seizures plus type2-a new missense mutation of SCN1A found in the pedigree of several patients with complex febrile seizures[J].Epilepsy Res,2005,63(2-3):151-156.
[19]Gambardella A,Marini C.Clinical spectrum of SCN1A mutation[J].Epilepsia,2009,50(suppl5):20-23.
[20]于美娟,陈俐,高玫梅,等.具有SCN1A基因错义突变(R1596C)的遗传性GEFS+家系1例报道[J].现代医院,2009,9(12):3-5.
[21]王海霞,王莹.刘定干.真核生物mRNA3]非翻译区的功能[J].生物化学与生物物理进展,2008,35(9):980—985.
[22]Zeng T,Dong ZF,Liu SJ,et al.A novel variant in the 3'UTR of human SCNIA gene from a patient with Dravet syndrome decreases mRNA stability mediated by GAPDH's binding[J].Hum Genet,2014,(133):801-811.
[23]冯超,唐宁,方绍海.等.法洛四联症患儿NOTCH2基因3'UTR区域突变分析[J].上海交通大学学报(医学版).2015,35(4):476-482.
[24]Zhang HS,Wu QY,Xu M.Mitogen-activated protein kinase signal pathways play an important rule in right ventricular hypertrophy of tetralogy of Fallot[J].Chin Med,2012,125(13):2243-2249.
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