A GENE FOR HEREDITARY PAROXYSMAL CEREBELLAR-ATAXIA MAPS TO CHROMOSOME19P

Hereditary paroxysmal cerebellar ataxia (HPCA) is an autosomal dominan t disorder characterized by the recurrence of intermittent attacks of vestibulocerebellar ataxia lasting from 15 minutes to a few days. The number of attacks is often significantly decreased by acetazolamide tr eatment. Neurological examination shows a permanent gaze-evoked nystag mus, as well as a mild cerebellar ataxia in most patients. The paroxys mal feature of this condition is shared by another autosomal dominant neurological condition, familial hemiplegic migraine (FHM), a conditio n in which permanent cerebellar signs have also been reported in some families. Although hemiplegic migraine has never been reported in pati ents with HPCA, we hypothesized, based on the latter observations, tha t HPCA and FHM may be allelic disorders. We previously mapped a gene r esponsible for FHM on the short arm of chromosome 19. We performed lin kage analysis with 6 markers spanning the FHM interval on a large HPCA family. Significant lod scores were obtained with 3 markers: D19S244 (LS = 3.71), D19S221 (3.60), and D19S226 (3.54) at theta = 0. Haplotyp e and multipoint linkage analysis established that the most likely loc ation was the same interval of 30 cM encompassing the chromosome 19 FH M locus.