发作性运动诱发性运动障碍一家系致病基因定位与突变分析

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.

Genetic mapping and mutation analysis in a family with paroxysmal kinesigenic dystonia