摘要目的 通过3个1p36区域的拷贝数变异病例,探讨1p36区PEX10基因与该区域拷贝数变异并发癫痫的相关性.方法 应用高分辨染色体显带、多重连接依赖性探针扩增(multiplex ligationdependent probe amplification,MLPA)、荧光原位杂交(fluorescence in situ hybridization,FISH)结合单核苷酸多态阵列(single nucleotide polymorphism array,SNP)芯片技术确定3例患者的核型,应用实时PCR检测患者外周血中PEX10基因的mRNA表达水平.结果 高分辨染色体检测未检出3例患者核型异常,MLPA分析显示3例患者均存在1p亚端粒区拷贝数变异,FISH证实该区域拷贝数变异,SNP芯片确认该区域变异范围,其中例1和例2有癫痫的症状,拷贝数异常区域包括PEX10基因,而例3无癫痫的症状,其PEX10基因拷贝数正常.家系分析显示3例均为新发生的染色体异常.实时PCR发现,与正常人相比,例1的PEX10基因的mRNA水平表达量提高,例2的PEX10基因的mRNA水平表达量降低.结论 PEX10基因的拷贝数变异导致PEX10基因mRNA水平表达异常,可能与该区域伴发的癫痫有关.

abstractsObjective To assess the association of PEX10 gene and 1p36 copy number variations in 1p36 region with concurrent epilepsy through analyzing 3 cases.Methods The karyotypes of 3 patients were determined by high resolution chromosome banding,multiplex ligation-dependent probe amplification (MLPA),fluorescence in situ hybridization (FISH) combined with single nucleotide polymorphism array (SNP) technology.Real-time PCR was carried out to determine the mRNA levels of PEX10 gene in peripheral blood of the patients.Results No abnormality was found upon high resolution karyotyping.MLPA analysis showed that all of the 3 patients had a copy number variation of subtelomeric region in the short arm of chromosome 1,which was confirmed by FISH and SNP chip analyses.Case 1 and case 2 both had an epilepsy phenotype,and their copy number variations have encompassed the PEX10 gene.On the other hand,case 3 has absent epilepsy,and its PEX10 gene copy number was normal.Family investigation confirmed that the chromosome abnormalities in all of the 3 cases were of de novo type.Compared with healthy controls,real time-PCR showed that mRNA of the PEX10 gene was increased in case 1 but decreased in case 2.Conclusion The abnormal expression of PEX10 gene resulting from copy number variations of 1p36 region may be associated with the epilepsy phenotype.