Clinic Analysis And Gene Mapping Of Familial Paroxysmal Kinesigenic Dyskinsia

Objective: Paroxysmal kinesigenic dyskinesia (PKD) is a rareneurologic inherited disease that has been reported by Kertesz in 1967.It occurs in both sporadic and familial forms. The inherited forms of PKDinclude autosomal dominant(AD) and antosomal recessive(AR). Bygenetic linkage analysis, there are two loci for PKD have been mapped to16 chromosome: 16p11.2-q12.1(EKD1), 16q13-q22.1 (EKD2). However,no gene responsible for PKD has been identified so far. We collected 6PKD pedigrees that from Chinese mainland, clincal and genetic analysiswere performed to localize the locus of them.Method: 6 large pedigrees including 122 members werefollowed-up, clinical information was analysised. Microsatellites markerscorresponding to pericentrometri region were used in parametric andnonparametric linkage analysis in 2 of these pedigrees.Result: There were 122 members in all, including 26 affected. All ofthe affected individuals had the pure and typical PKD phenotype.According to new diagnostic criteria of Bruno, they were diagnosed aspure PKD. The genetic inheritance showed not only autosomal dominant(AD), but also autosomal recessive (AR). Through analysis, we foundthat in the 4 AD pedigrees, the onset age was earlier and the severity wasincreasing in the subsequent generations, which suggested geneticanticipation. Linkage analysis has been applied in two of these pedigrees.The maximum LOD score and NPL score were negative, P values weresignificantly larger than 0.05. It showed no evidence of association withknown PKD loci in both pedigrees, providing evidence for a novel PKDlocus.Conclusion: PKD is a clinically and genetically heterogeneousneurogenerative disorder, it can be inherited in an AD or AR mode. Genetic anticipation was founded in Chinese AD PKD pedigrees.Linkage analysis also suggested a novel PKD locus in pure Chinese ADpedigrees.