A locus for paroxysmal kinesigenic dyskinesia maps to human chromosome 16

Objective: To use genetic linkage analysis to localize a gene for paroxysmal kinesigenic dyskinesia (PKD) in a three generation African-American kindred. Background: PKD is a rare autosomal dominant disorder characterized by episodic choreiform or dystonic movements that are brought on or exacerbated by voluntary movement. There are individuals with the clinical features of PKD but with no family history of the disease, but whether these sporadic cases represent spontaneous mutations of PKD or have a distinct condition is unknown. Methods: A genome-wide linkage scan of polymorphic microsatellites at 25 cM resolution was performed to localize a gene for PKD in one African-American kindred. Pairwise multipoint linkage analyses were performed at different penetrance estimates. Results: Evidence for linkage of the kinesigenic form of paroxysmal dyskinesia to chromosome 16 was obtained. A maximum lod score of 4.40 at θ = 0 was obtained with D16S419. Critical recombinants place the PKD gene between D16S3100 and D16S771. Conclusions: A paroxysmal kinesigenic dyskinesia (PKD) locus lies within an 18 cM interval on 16p11.2-q11.2, between D16S3100 and D16S771. A gene for infantile convulsions with paroxysmal choreoathetosis has also been mapped to this region. These two regions overlap by approximately 6 cM. These two diseases could be caused by different mutations in the same gene or two distinct genes may lie within this region.