Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland Chinese patients and clinical and molecular characterization of spinocerebellar ataxia type 6.
BACKGROUND
Dominantly inherited spinocerebellar ataxia (SCA) is a clinically and genetically heterogeneous group of neurodegenerative disorders. This study was to further assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, SCA8, SCA10, SCA12, SCA14, SCA17 and DRPLA (dentatorubro-pallidoluysian atrophy) in mainland Chinese, and to specifically characterize mainland Chinese patients with SCA6 in terms of clinical and molecular features.


METHODS
Using a molecular approach, we investigated SCA in 120 mainland Chinese families with dominantly inherited ataxias and in 60 mainland Chinese patients with sporadic ataxias. Clinical and molecular features of SCA6 were further characterized in 13 patients from 4 families.


RESULTS
SCA3/MJD was the most common type of autosomal dominant SCA in mainland Chinese, accounting for 83 patients from 59 families (49.2%), followed by SCA2 [8 (6.7%)], SCA1 [7 (5.8%)], SCA6 [4 (3.3%)], SCA7 [1 (0.8%)], SCA8 (0%), SCA10 (0%), SCA12 (0%), SCA14 (0%), SCA17 (0%) and DRPLA (0%). The genes responsible for 41 (34.2%) of dominantly inherited SCA families remain to be determined. Among the 60 patients with sporadic ataxias in the present series, 3 (5.0%) was found to harbor SCA3 mutations while none was found to harbor SCA6 mutations. In the 4 families with SCA6, significant anticipation was found in the absence of genetic instability on transmission.


CONCLUSIONS
A geographic cluster of families with SCA6 subtype was initially identified in a mainland Chinese population.
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
Hong
H
Jiang
Bei-sha
BS
Tang
Bo
B
Xu
Guo-hua
GH
Zhao
Lu
L
Shen
Jian-guang
JG
Tang
Qing-hua
QH
Li
Kun
K
Xia
D000328:Adult; D044466:Asian People; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type