Goto J, Masuda N, Watanabe M, Kanazawa I
Department of Neurology, School of Medicine, University of Tokyo.
Rinsho Shinkeigaku. 1995 Dec;35(12):1529-31.
Huntington's disease (HD) is a progressive neurodegenerative disorder which is clinically characterized by chorea, cognitive decline, and emotional disturbance; it is inherited in an autosomal dominant manner. The HD gene maps to chromosome 4p16.3. Our linkage analysis demonstrated a significant genetic linkage between Japanese HD families and the flanking markers, D4S127, D4S43. The molecular basis of the disease is an expansion of CAG repeat in the huntingtin gene. We performed molecular analysis of the repeat in Japanese HD patients and normal controls. The size of the CAG repeat ranged from 37 to 95 repeats in affected subjects and from seven to 29 in normal controls. A significant correlation was found between the age of onset and the CAG expansion. The length of the expanded repeat is unstable in meiotic transmission and large increases occur in paternal transmission. At the same time the CCG repeat polymorphism adjacent to the CAG repeat was analysed and haplotypes of HD chromosomes were identified. Striking linkage disequilibrium was found between the CAG repeat expansion and an allele of (CCG)10 in Japanese HD chromosome. It is distinct from that described previously in western populations. Western HD chromosomes strongly associate with an allele of (CCG)7.
亨廷顿舞蹈症（HD）是一种进行性神经退行性疾病，临床特征为舞蹈症、认知衰退和情绪障碍；它以常染色体显性方式遗传。HD基因定位于4号染色体的p16.3区域。我们的连锁分析表明，日本HD家族与侧翼标记D4S127、D4S43之间存在显著的遗传连锁。该疾病的分子基础是亨廷顿基因中CAG重复序列的扩增。我们对日本HD患者和正常对照的该重复序列进行了分子分析。在患病个体中，CAG重复序列的大小范围为37至95次重复，而在正常对照中为7至29次。发病年龄与CAG扩增之间存在显著相关性。扩增重复序列的长度在减数分裂传递中不稳定，在父系传递中会大幅增加。同时，对与CAG重复序列相邻的CCG重复多态性进行了分析，并确定了HD染色体的单倍型。在日本HD染色体中，发现CAG重复序列扩增与（CCG）10等位基因之间存在显著的连锁不平衡。这与先前在西方人群中描述的情况不同。西方HD染色体与（CCG）7等位基因强烈相关。
