Molecular pathology of dentatorubral-pallidoluysian atrophy

被引:16
作者
Kanazawa, I [1 ]
机构
[1] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo 1138655, Japan
关键词
dentate nucleus; external segment of pallidum; anticipation; CAG repeat disease; atrophin; 1; intranuclear inclusion body;
D O I
10.1098/rstb.1999.0460
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dentatorubral - pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. Cardinal pathological features of DRPLA are a combined degeneration of both the dentatorubral and the pallidoluysian systems. Although the early sporadic cases were reported by Western neuropathologists, a strong heritability and an age of onset-dependent variability of the clinical features were carefully deduced by Japanese clinicians. The disease is fairly common in Japan , but extremely rare in Caucasians. Since the gene was identified in 1994, DRPLA is known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin 1. DRPLA shows prominent 'anticipation', which is genetically clearly explained by a marked instability of the expanded CAG repeat length during spermatogenesis. Moreover, the instability of the CAG repeat length also seems to occur in the somatic cells, resulting in 'somatic mosaicism'. Possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of molecular pathological points of view.
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收藏
页码:1069 / 1074
页数:6
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