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Molecular and Clinical Study of Spinocerebellar Ataxia Type 7 in Chinese Kindreds
Weihong Gu, MD;
Yanqi Wang, MD;
Xingzhou Liu, MD;
Baoyu Zhou, MD;
Yongxing Zhou, MD, PhD;
Guoxiang Wang, MD, PhD
Arch Neurol. 2000;57:1513-1518.
Objective To investigate the clinical and molecular characteristics of spinocerebellar ataxia type 7 (SCA7) in Chinese kindreds.
Background Spinocerebellar ataxia type 7 is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene.
Methods Clinical and related examinations were performed in all affected or at-risk individuals from 4 Chinese families presenting with autosomal dominant cerebellar ataxia and decreased visual acuity. The size of the (CAG)n array of the SCA7 gene was detected by polymerase chain reaction, polyacrylamide gel electrophoresis, and related techniques in the 4 families and 67 healthy controls. The relationship between expanded repeat number and age of onset was statistically analyzed.
Results The SCA7 mutation was identified in 2 families. Clinical study revealed that great variation occurred in the age of onset, initial symptoms, and associated signs. Meanwhile, the analysis of 11 parent-child couples demonstrated the existence of marked anticipation. Some distinct retinal changes were noted in 2 affected patients. All SCA7 patients in our series exhibited expanded CAG repeats, ranging from 44 to 85 repeats, with a strong negative correlation between repeat size and age of onset. Repeat lengths of expanded alleles showed somatic mosaicism in leukocyte DNA. There were some subtle clinical differences between the SCA7-positive and -negative cases.
Conclusions Clinical variation occurred not only among the SCA7 families but also within the same kindred. Meiotic and mitotic instability of the CAG repeat in the SCA7 gene were demonstrated, and intergenerational instability of the array was associated with the clinical phenomenon of anticipation.
From the Departments of Neurology (Drs Gu, Liu, B. Zhou, Y. Zhou, and G. Wang) and Ophthalmology (Dr Y. Wang), China-Japan Friendship Hospital, Beijing, China.
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