I. Yamashita et al., A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter, ANN NEUROL, 48(2), 2000, pp. 156-163
Dominantly inherited, late-onset pure cerebellar ataxia is a group of genet
ically heterogeneous neurodegenerative disorders. Approximately half of the
se disorders in the Japanese population are caused by moderate expansion of
a CAG repeat in the coding region of the CACNA1A gene on chromosome 19p13
(SCA6). However, neither the loci nor the specific mutations for the remain
ing disorders have been determined. We performed systematic linkage analysi
s in a three-generation Japanese family with a locus or mutation that diffe
red from those of known spinocerebellar ataxias. The family members with a
late onset (greater than or equal to 39 years old) exhibited pure cerebella
r ataxia, whereas those with an early onset (less than or equal to 27 years
old) first showed intermittent axial myoclonus followed by ataxia. Other n
eurological signs were sparse, and neuroimaging studies revealed that atrop
hy was confined to the cerebellum. Multipoint analysis and haplotype recons
truction ultimately traced this novel spinocerebellar ataxia locus (SCA14)
to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-
qter (Zmax = 4.08, corrected for age-dependent penetrance).