Abstract：
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is a neurodegenerative disease caused by expanded polyglutamine repeats in exon 10 of the ataxin-3 gene, ATXN3. The accumulation of mutant ATXN3 protein leads to severe clinical manifestations and premature death. Clinically, SCA3 pathology is characterized by progressive ataxia leading to motor incoordination that may affect balance, gait and speech, and neuropathologically by a progressive degeneration of the spinal cord and cerebellum, as well as the cerebral cortex and basal ganglia. Although SCA3 is a rare disease, it is the most common autosomal dominant spinocerebellar ataxia worldwide. Its geographical distribution varies worldwide, with peak prevalence in certain regions of Brazil, Portugal and China. In 1994, the identification of the polyglutamine expansion in the ATXN3 gene made it possible not only to diagnose this pathology but also to dissect the mechanisms leading to cellular degeneration. As a monogenic disease for which only symptomatic treatment is available, the ATXN3 gene represents an attractive therapeutic target for gene editing strategies.
摘要：
脊髓小脑共济失调3型(SCA3),也被称为马查多-约瑟夫病，是由ataxin-3基因外显子10中扩增的多聚谷氨酰胺重复序列引起的神经退行性疾病，ATXN3.突变ATXN3蛋白的积累导致严重的临床表现和过早死亡。临床上,SCA3病理学的特点是进行性共济失调，导致运动不协调，可能影响平衡，步态和言语，和神经病理学上的脊髓和小脑的进行性变性，以及大脑皮层和基底神经节.虽然SCA3是一种罕见的疾病，它是世界上最常见的常染色体显性遗传性脊髓小脑共济失调。它的地理分布在世界各地各不相同，巴西某些地区的患病率最高，葡萄牙和中国。1994年，ATXN3基因中聚谷氨酰胺扩增的鉴定使不仅可以诊断这种病理，而且可以剖析导致细胞变性的机制。作为一种单基因疾病，只有对症治疗可用，ATXN3基因是基因编辑策略的一个有吸引力的治疗靶点.
