Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias
K. F. Damji, R. R. Allingham, S. C. Pollock, K. Small, K. E. Lewis, J. M. Stajich, L. H. Yamaoka, J. M. Vance and M. A. Pericak-Vance
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
BACKGROUND: Periodic vestibulocerebellar ataxia is an autosomal dominant
disorder characterized by defective smooth pursuit, gaze-evoked nystagmus,
ataxia, and vertigo. The age of onset ranges from the third to the sixth
decade. To date, all patients have originated from North Carolina,
suggesting a single common founder. OBJECTIVE: To clarify the
classification of periodic vestibulocerebellar ataxia by determining
whether it is allelic to other autosomal dominant cerebellar ataxias for
which genes have been either localized or identified. METHODS: Blood was
collected and DNA isolated from 66 subjects (19 affected individuals) in
two multigenerational families. The microsatellite markers used in the
analysis either flanked or were tightly linked to the disease gene regions.
Two-point and multipoint linkage analyses were performed to define the
limits of exclusion. RESULTS: Periodic vestibulocerebellar ataxia was
excluded from loci linked to spinocerebellar ataxia type 1 (chromosome 6p),
type 2 (chromosome 12q) type 3/Machado/Joseph disease (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 hereditary paroxysmal cerebellar ataxia
(chromosome 19p), and dentatorubral-pallidoluysian atrophy/Haw River
syndrome (chromosome 12p). CONCLUSION: Periodic vestibulocerebellar ataxia
is genetically distinct from those autosomal dominant ataxias for which
chromosomal localization has been established.
