PAROXYSMAL DYSTONIC CHOREOATHETOSIS - TIGHT LINKAGE TO CHROMOSOME 2Q

Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at re st both spontaneously and following caffeine or alcohol consumption. W e analyzed a Polish-American kindred with autosomal dominant PDC and i dentified tight linkage between the disorder and microsatellite marker s on chromosome 2q (maximum two-point LOD score 4.77; recombination fr action 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three ot her paroxysmal neurological disorders (periodic ataxia with myokymia a nd hypo- and hyperkalemic periodic paralysis) are due to mutation in i on-channel genes raises the possibility that PDC is also due to an ion -channel gene mutation. It is noteworthy that a cluster of sodium-chan nel genes is located on distal chromosome 2q, near the PDC locus. Iden tifying the PDC locus on chromosome 2q will facilitate discovery of th e PDC gene and enable investigators to determine whether PDC is geneti cally homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus.