FAMILIAL PERIODIC CEREBELLAR-ATAXIA WITHOUT MYOKYMIA MAPS TO A 19-CM REGION ON 19P13

Familial periodic cerebellar ataxia (FPCA) is a heterogenous group of rare autosomal dominant disorders characterized by episodic cerebellar disturbance, A potassium-channel gene (KCNA1) has been found to be re sponsible for one of its subgroups, familial periodic cerebellar ataxi a with myokymia (FPCA/+M; MIM 160120). A different subgroup that is no t associated with myokymia (FPCA/-M; MIM 108500) was recently mapped t o chromosome 19p. Here we have performed linkage analysis in two large families with FPCA/-M that also demonstrated neurodegenerative pathol ogy of the cerebellum. Three markers in 19p13 gave significant lod sco res (>3.0), while linkage to KCNA1 and three known loci for spinocereb ellar ataxia (SCAI, SCA2, and SCA3) was excluded. The highest lod scor e was obtained with the marker D19S413 (4.4 at recombination fraction 0), and identification of meiotic recombinants in affected individuals placed the locus between the flanking markers D19S406 and D19S226, na rrowing the interval to 19 cM. A CAG trinucleotide-repeat expansion wa s detected in one family but did not cosegregate with the disease.