儿童失神癫癎的单体型相对风险和传递不平衡分析  

Analysis of haplotype-based haplotype relative risk and transmission disequilibrium test in childhood absence epilepsy

作　　者：葛欣[1] 王治平[1] 张雅芬[2] 邵新华[1] 鲍克容[1] 

机构地区：[1]上海第二医科大学附属新华医院上海儿童医学中心小儿神经内科,200092 [2]上海儿科医学研究所生化室

出　　处：《中华儿科杂志》2003年第9期675-679,共5页Chinese Journal of Pediatrics

摘　　要：目的　确认中国儿童失神癫 (childhoodabsenceepilepsy ,CAE)是否与染色体 8q2 4连锁。方法　选取染色体 8q2 4上 5个微卫星DNA标记 (D8S554、D8S53 4、D8S110 0、D8S1783、D8S1753 ) ,对3 0个CAE核心家系的患儿及其父母的单体型进行分析 ,另有 10个正常家系作为对照。从外周血白细胞中常规抽提基因组DNA ,应用PCR方法扩增各个微卫星片断 ,PCR产物用基因测序确定各个等位基因的长度。统计学方法选用基于单体型的单体型相对风险 (HHRR)和传递不平衡检验 (TDT)分析。结果　经HHRR分析显示 ,D8S5544χ2 =5 93 9(P <0 0 5)、D8S110 0 3 χ2 =5 0 81(P <0 0 5)、D8S1783 6χ2 =4 3 0 8,(P <0 0 5) ,差异有显著性 ;TDT显示D8S5544χ2 =4 46(P <0 0 5)、D8S1783 6 χ2 =4(P <0 0 5) ,差异有显著性。为了排除HHRR和TDT分析可能存在的假关联 ,我们对所有患儿家系作了详细的分析 ,结果发现只有在位点D8S1783提示与CAE致病基因存在传递不平衡 ,而另二个位点均为假关联。结论　①中国儿童失神癫可能与染色体 8q2 4连锁 ,与位点D8S1783存在传递不平衡 ;结合国外的结论 ,CAE致病基因可能存在于染色体 8q2 4上的ECA1区域内。②CAE基因在不同地区、不同种族的人群中可能存在遗传异质性。③对于核心家系 。Objective Childhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 8%-15% of all childhood epilepsies A positive family history of epilepsy, a hereditary factor being one of the pathogeneses, is found in 15%-44% of children with absence seizures The phenotype of CAE is specific (including seizure forms and EEG), therefore it is suitable for genetic study The purpose of this study was to confirm the linkage of childhood absence epilepsy to chromosome 8q24 in China Methods Twenty nine trios families (a patient and his/her parents) as patient group and 10 normal trios families as control group were investigated for chromosome 8q24 by haplotype analysis with 5 microsatellite DNA markers (D8S554, D8S534, D8S1100, D8S1783, D8S1753) Genomic DNA was isolated from 4 ml human peripheral blood by using the conventional procedure, and then was treated using the PCR method PCR products were analyzed by gene scan Statistical methodology included haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) Results In this study, the polymorphism information content (PIC) of 5 microsatellite DNA markers were: 0 519, 0 828, 0 528, 0 654 and 0 772 HHRR showed D8S554 4 (χ 2=5 939, P <0 05), D8S1100 3 (χ 2= 5 081, P <0 05), D8S1783 6 (χ 2=4 308, P <0 05) TDT showed D8S554 4 (χ 2=4 46, P <0 05), D8S1783 6 (χ 2=4, P <0 05) In order to exclude false association results, the authors analyzed every family in detail Four trios families transmitted allele D8S1783 6 to their offspring, and the same allele hasn′t been found in controls The further work showed that locus D8S1783 had transmission disequilibrium with CAE, the other two loci were a false association Conclusion ①Childhood absence epilepsy in the Chinese population may be linked to chromosome 8q24, the CAE gene is transmitted disequilibrium on locus D8S1783 Combined with other research results, we suppose that CAE gene may

关 键 词：儿童 失神性癫痫 遗传多态性 微卫星DNA标记 连锁不平衡 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学]