PERIODIC VESTIBULOCEREBELLAR ATAXIA, AN AUTOSOMAL-DOMINANT ATAXIA WITH DEFECTIVE SMOOTH-PURSUIT, IS GENETICALLY DISTINCT FROM OTHER AUTOSOMAL-DOMINANT ATAXIAS

Background: Periodic vestibulocerebellar ataxia is an autosomal domina nt disorder characterized by defective smooth pursuit, gaze-evoked nys tagmus, ataxia, and vertigo. The age of onset ranges from the third to the sixth decade. To date, all patients have originated from North Ca rolina, suggesting a single common founder. Objective: To clarify the classification of periodic vestibulocerebellar ataxia by determining w hether it is allelic to other autosomal dominant cerebellar ataxias fo r which genes have been either localized or identified. Methods: Blood was collected and DNA isolated from 66 subjects (19 affected individu als) in two multigenerational families. The microsatellite markers use d in the analysis either flanked or were tightly linked to the disease gene regions. Two-point and multipoint linkage analyses were performe d to define the limits of exclusion. Results: Periodic vestibulocerebe llar ataxia was excluded from loci linked to spinocerebellar ataxia ty pe 1 (chromosome 6p), type 2 (chromosome 12q), type 3/Machado-Joseph d isease (chromosome 14q), type 4 (chromosome 16q), and type 5 (11cent) as well as to episodic ataxia with myokymia (chromosome 12p), episodic ataxia with nystagmus (chromosome 19p), acetazolamide-responsive here ditary paroxysmal cerebellar ataxia (chromosome 19p), and dentatontbra lpallidoluysian atrophy/Haw River syndrome (chromosome 12p). Conclusio n: Periodic vestibulocerebellar ataxia is genetically distinct from th ose autosomal dominant ataxias for which chromosomal localization has been established.