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Spinocerebellar Ataxia Type 1 in China
Molecular Analysis and Genotype-Phenotype Correlation in 5 Families
Yong-Xing Zhou, MD, PhD;
Wen-Hui Qiao, MD;
Wei-Hong Gu, MD;
Heng Xie, MD, PhD, MPH;
Bei-Sha Tang, MD;
Lian-Sheng Zhou, MD;
Bin-Xian Yang, MD;
Yoshihisa Takiyama, MD, PhD;
Shoji Tsuji, MD, PhD;
Hui-Yu He, MD;
Chu-Xia Deng, PhD;
Lev G. Goldfarb, MD, PhD;
Guo-Xiang Wang, MD, PhD
Arch Neurol. 2001;58:789-794.
Background Twelve genetic types of autosomal dominant hereditary ataxia have been
recently identified and the genes responsible for most of them cloned. Molecular
identification of the type of ataxia is important to determine the disease
prevalence and its natural history in various populations.
Objectives To perform molecular analysis of 75 Chinese families affected with spinocerebellar
ataxia (SCA) and to evaluate the spectrum of mutations in these genes and
the correlation between genotypes and phenotypes in Chinese patients.
Setting Neurogenetics Unit, China-Japan Friendship Hospital, Beijing, China.
Methods One hundred nine patients from 75 kindreds diagnosed as having autosomal
dominant SCA, 16 patients with sporadic SCA or spastic paraplegia, 280 control
chromosomes of the Chinese population, and 120 control chromosomes of the
Sakha population were selected for this study. We conducted detailed mutational
analysis by direct sequencing of polymerase chain reaction products amplified
from genomic DNA.
Results Spinocerebellar ataxia type 1 (SCA1) was identified in 5 families with
12 studied patients. All affected family members were heterozygous for a CAG
repeat expansion in the SCA1 gene containing 51 to
64 trinucleotide repeats. Normal alleles had 26 to 35 repeats. Spinocerebellar
ataxia type 1 accounted for 7% of the studied Chinese families with ataxia.
In addition, we determined the frequency of a single vs double CAT interruption
in 120 control chromosomes of the Siberian Sakha population, which has the
highest known prevalence of SCA1, and compared this with 280 control chromosomes
from the Chinese populations. The results show that 64.7% of the Siberian
normal alleles contain a single CAT interruption, whereas 92% of the Chinese
had more than 1 interruption.
Conclusions Spinocerebellar ataxia type 1 is responsible for 7% of affected families
in the Chinese population. A correlation between the prevalence of SCA1 and
the number of CAT interruptions in the trinucleotide chain suggests that a
CAT-to-CAG substitution may have been the initial event contributing to the
generation of expanded alleles and influencing relative prevalence of SCA1.
From the Neurogenetics Unit, Department of Neurology, China-Japan Friendship
Hospital, Hepingli, Beijing, China (Drs Y.-X. Zhou, Gu, Yang, He, and Wang);
Clinical Neurogenetics Unit, Medical Neurology Branch, National Institute
of Neurological Disorders and Stroke (Drs Y.-X. Zhou and Goldfarb) and Genetics
of Development and Disease Branch (Drs Y.-X. Zhou, Qiao, and Deng), and Division
of Cancer Epidemiology and Genetics, National Cancer Institute (Dr Xie), National
Institutes of Health, Bethesda, Md; Institute of Neurology, Hunan Medical
University, Changsha, China (Dr Tang); Department of Neurology, The First
People's Hospital of Xuzhou, Xuzhou, China (Dr L.-S. Zhou); Department of
Neurology, Jichi Medical School, Minamikawachi, Tochigi, Japan (Dr Takiyama);
and Department of Neurology, Brain Research Institute, Niigata University,
Niigata, Japan (Dr Tsuji).
Corresponding author and reprints: Yong-Xing Zhou, MD, PhD, Genetics
of Development and Disease Branch, Bldg 10/9N104, NIDDK, NIH, 10 Center Dr
Bethesda, MD 20892.
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