Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attack s of involuntary movements induced by sudden voluntary movements. Some pati ents with PKC have a history of infantile afebrile convulsions with a favor able outcome. To localize the PKC locus, we performed genomewide linkage an alysis on eight Japanese families with autosomal dominant PKC. Two-point li nkage analysis provided a maximum LOD score of 10.27 (recombination fractio n [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multi point LOD score for a subset of markers was calculated to be 11.51 (p = 0.8 ) at D16S3080. Haplotype analysis defined the disease locus within a region of similar to 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile c onvulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recogni zed clinical entity with benign infantile convulsions and nonkinesigenic pa roxysmal dyskinesias.