Localization And Analysis Of Mutation In A Primary Paroxysmal Kinesigenic Dystonia Family

Backgroundparoxysmal kinesigenic dystonia(PKD)is a rare paroxysmal movement disorder characterized by recurrent and brief attack of choreiform or dystonic movement triggered by sudden voluntary movement.Consciousness is preserved.The genetic inheritance showed not only autosomal dominant(AD),but also autosomal recessive (AR).Most cases are familial with autosomal dominant inheritance.By genetic linkage anakysis,there are two loci mapped to chromosome 16 for PKD:EKD1(16p11.2-q12.1),EKD2(16q13-q22).Later,the following analysis excluded the PKD locus in a British pure PKD family from chromosome 16,providing evidence for a novel locus.Now,the causative genes have not been identified.It is reported that one of the two genes,ITGAL and SCNNlG,could be causative for PKD.It is of importance to search for a causative gene and study the pathophysiology for PKD.ObjectiveThe purpose of the study is to localize the causative region and detected the causative mutation.MethodsA PKD family in Hunan Province was recruited.Clinical information of this family was analyzed.Fourteer microsatellite markers on chromosome 16 were selected and genotyped,which covered the known disease loci.After preliminary localizatioa,ITGAL and SCNNlG genes were detected by sequencing.ResultsThere were 10 members in all,including 5 affected.According to new diagnostic criteria of Bruno,they were diagnosed as PKD.The maximal two-point LOD score was obtained in D16S3396 and D16S 3057 with 1.47.The haplotype analysis revealed almost all of affected individuals carried the same haplotype.No disease-causing mutation was found by direct sequencing.Eight sequence variations were detected in ITGAL and SCNNlG genes,which were IVS9-22T＞C,IVS12-20A＞G,IVS19-73A＞G in ITGAL;IVS2-4C＞G,c.-31A＞G,c.387T＞C,c.474T＞C,IVS5+62G＞C in SCNNlG All these variations were reported SNP.Conclusion1.Our results suggested that the causative region of the PKD family with infantile convulsion was related to the interval between D16S401 and D16S5032.ITGAL and SCNNlG were ruled out in a Chinese PKD family as causative genes.