Genetic Study of Paroxysmal Kinesigenic Choreoathetosis

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Paroxysmal kinesigenic choreoathetosis (PKC), is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements or startle response. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To confirm the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC.Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination Fraction [θ]=.00 ; penetrance [p]=.7) at marker D16S3081, and a maximum multipoint 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〜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 16p12.1, 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 convulsions and paroxysmal choreoathetosis" (ICCA) (MIM 602066). Then, we performed the candidate gene analysis, those are known to locate in the PKCR.Some candidate genes that have been mapped either between D16S3093 and D16S416 include the interleukin-4-receptor α-chain gene (IL4R [MIM 147781]), the adenylate cyclase-7 gene (ADCY7 [MIM 6003585]), the protein phosphatase-4 catalytic subunit gene (PPP4C [MIM 602035]), and the monoamine-preferring sulfotransferase gene (STM [MIM 600641]), did not link to the PKC.We are doing the collaborative study of newly discovered molecule, which has been mapped in PKCR.