MAPPING THE GENE FOR ACETAZOLAMIDE RESPONSIVE HEREDITARY PARYOXYSMAL CEREBELLAR-ATAXIA TO CHROMOSOME 19P

Acetazolamide responsive hereditary paroxysmal cerebellar ataxia (APCA ) is a rare autosomal dominant disorder characterized by attacks of ce rebellar ataxia and dysarthria with normal or near normal neurologic f unction between attacks. A genome-wide search using polymorphic di- an d tri-nucleotide repeats was initiated and the APCA locus was found to be linked to the short arm of chromosome 19 in two large kindreds. Th e microsatellite marker UT705 was found to be linked to the APCA locus with two point analysis yielding a maximum lod score of 8.20 at theta (max) = 0.000 in a five generation pedigree. Linkage to this region wa s confirmed in a second kindred. The absence of known candidate genes in the region may necessitate a positional cloning approach in order t o identify the gene for this disorder.