CAJ | 학술논문

目的探讨发作性运动诱发性运动障碍(PKD)家系临床特点,定位致病基因和检测突变.方法对1个PKD家系的患者及其亲属进行临床资料分析,采集外周静脉血标本提取基因组DNA.选取16号染色体目前已报道位点内的微卫星标记,采用多重PCR技术对该家系进行连锁分析;普通PCR方法扩增候选基因SCNN1G和ITGAL外显子及毗邻序列,进行测序及家系共分离检测.结果该家系3代12人,共5例患者.连锁分析提示当重组率(0)为0.0时在D16S3396和D16S3057处取得最大两点LOD值1.47,支持连锁.所有患者均携带完全相同的单体型并与疾病表型共分离.ITGAL、SCNN1G测序共发现8个序列变异,但均为已报道的单核苷酸多态(SNP),未发现家系共分离的致病性突变.结论该PKD家系致病基因与位于16号染色体上已报道的PKD遗传位点连锁,进一步证明其为PKD的重要遗传位点;基本排除SCNN1G和ITGAL为该家系的致病基因,其致病基因有待进一步探索.
목적 탐토발작성운동유발성운동장애(PKD)가계림상특점,정위치병기인화검측돌변.방법 대1개PKD가계적환자급기친속진행림상자료분석,채집외주정맥혈표본제취기인조DNA.선취16호염색체목전이보도위점내적미위성표기,채용다중PCR기술대해가계진행련쇄분석;보통PCR방법확증후선기인SCNN1G화ITGAL외현자급비린서렬,진행측서급가계공분리검측.결과 해가계3대12인,공5례환자.련쇄분석제시당중조솔(0)위0.0시재D16S3396화D16S3057처취득최대량점LOD치1.47,지지련쇄.소유환자균휴대완전상동적단체형병여질병표형공분리.ITGAL、SCNN1G측서공발현8개서렬변이,단균위이보도적단핵감산다태(SNP),미발현가계공분리적치병성돌변.결론 해PKD가계치병기인여위우16호염색체상이보도적PKD유전위점련쇄,진일보증명기위PKD적중요유전위점;기본배제SCNN1G화ITGAL위해가계적치병기인,기치병기인유대진일보탐색.
Objective To study the clinical characteristics and genetic cause of a Chinese family affected with paroxysmal kinesigenic dystonia(PKD).Methods The detailed clinical data and the blood samples of the affected patients with PKD and their relatives were collected.After genomic DNA was extracted from blood leukocytes,target linkage analysis Was performed using multiplex PCR by microsatellite marker's located in the reported critical region on chromosome 16.All exons and flanking regions of SCNN1G and ITGAL genes were amplified by PCR-sequence.Results In this three-generation 12 member family,5 individuals have been diagnosed as PKD.Target linkage analysis suggested the disease gene linked to chromosome 16.between D16S3396 and D16S3057 with two-point LOD score of 1.47 at recombination fraction(θ)=0.0.All affected individuals shared a common haplotype which co-segregated with the phenotype.Except for 8 reported SNPs,no pathologic sequence variants were found in candidate genes SCNN1G and ITGAL.Conclusions The studied family is genetically linked to the reported critical locus of PKD on chromosome 16.SCNN1G and ITGAL were ruled out as the causative genes for the studied pedigree.Further genetic analysis in this family may reveal new genetic cause responsible for PKD.