Ge Xin, Wang Zhi-ping, Zhang Ya-fen, Shao Xin-hua, Bao Ke-rong
Department of Pediatric Neurology, Xinhua Hospital, Shanghai Children's Medical Center, Shanghai Second Medical University, Shanghai 200092, China.
Zhonghua Er Ke Za Zhi. 2003 Sep;41(9):675-9.
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.
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).
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) (chi(2) = 5.939, P < 0.05), D8S1100(3) (chi(2) = 5.081, P < 0.05), D8S1783(6) (chi(2) = 4.308, P < 0.05). TDT showed D8S554(4) (chi(2) = 4.46, P < 0.05), D8S1783(6) (chi(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.
(1) Childhood 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 be in the ECA1 area on chromosome 8q24. (2) The CAE gene perhaps has a genetic heterogeneity in the population of different areas and different races. (3) HHRR and TDT seem to be the best statistical methods to do linkage disequilibrium study in the trios family.
儿童失神癫痫（CAE）是特发性全身性癫痫的一种常见形式，占所有儿童癫痫的8% - 15%。癫痫家族史阳性，作为发病机制之一的遗传因素，在15% - 44%的失神发作儿童中被发现。CAE的表型具有特异性（包括发作形式和脑电图），因此适合进行遗传学研究。本研究的目的是在中国人群中证实儿童失神癫痫与8号染色体q24区域的连锁关系。
采用5个微卫星DNA标记（D8S554、D8S534、D8S1100、D8S1783、D8S1753）进行单倍型分析，对29个三联体家庭（一名患者及其父母）作为患者组和10个正常三联体家庭作为对照组进行8号染色体q24区域的研究。采用常规方法从4ml人外周血中分离基因组DNA，然后用PCR方法进行处理。PCR产物通过基因扫描进行分析。统计方法包括基于单倍型的单倍型相对风险（HHRR）和传递不平衡检验（TDT）。
本研究中，5个微卫星DNA标记的多态性信息含量（PIC）分别为：0.519、0.828、0.528、0.654和0.772。HHRR显示D8S554(4)（χ² = 5.939，P < 0.05）、D8S1100(3)（χ² = 5.081，P < 0.05）、D8S1783(6)（χ² = 4.308，P < 0.05）。TDT显示D8S554(4)（χ² = 4.46，P < 0.05）、D8S1783(6)（χ² = 4，P < 0.05）。为排除假关联结果，作者对每个家庭进行了详细分析。4个三联体家庭将等位基因D8S1783(6)传递给了他们的后代，而在对照组中未发现相同的等位基因。进一步的研究表明，位点D8S1783与CAE存在传递不平衡，另外两个位点是假关联。
（1）中国人群中的儿童失神癫痫可能与8号染色体q24区域连锁，CAE基因在D8S1783位点存在传递不平衡。结合其他研究结果，我们推测CAE基因可能位于8号染色体q24区域的ECA1区域。（2）CAE基因在不同地区和不同种族人群中可能存在遗传异质性。（3）HHRR和TDT似乎是三联体家庭连锁不平衡研究中最好的统计方法。
