A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6.
In order to clarify the clinical and genetic features of SCA6, we retrospectively analyzed 140 patients. We observed an inverse correlation between the age of onset and the length of the expanded allele, and also between the age of onset and the sum of CAG repeats in the normal and the expanded alleles. The ages of onset of four homozygous patients correlated better with the sum of CAG repeats in both alleles rather than with the expanded allele calculated from heterozygous SCA6 subjects. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. The results of neuro-otological examination performed in 22 patients suggested the purely cerebellar abnormalities of ocular movements in nature. There was a close relationship between downbeat positioning nystagmus (DPN) and positioning vertigo, which became more common in the later stage. We conclude that total number of CAG repeat-units in both alleles is a good parameter for assessment of age of onset in SCA6 including homozygous patients. In addition, clinical and neuro-otological examinations suggested that SCA6 is a disease with predominantly cerebellar dysfunction.
Takahashi
Hiroki
H
Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Ishikawa
Kinya
K
Tsutsumi
Takeshi
T
Fujigasaki
Hiroto
H
Kawata
Akihiro
A
Okiyama
Ryoichi
R
Fujita
Tsuneo
T
Yoshizawa
Kazuo
K
Yamaguchi
Shigeki
S
Tomiyasu
Hitoshi
H
Yoshii
Fumihito
F
Mitani
Kazuko
K
Shimizu
Natsue
N
Yamazaki
Mineo
M
Miyamoto
Tomoyuki
T
Orimo
Tomoyuki
T
Shoji
Shin'ichi
S
Kitamura
Ken
K
Mizusawa
Hidehiro
H
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D015220:Calcium Channels / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D018911:Trinucleotide Repeats / Q000235:genetics*; D014717:Vertigo / Q000150:complications; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D004247:DNA; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type