α-synuclein locus duplication as a cause of familial Parkinson's disease
α-synuclein locus duplication as a cause of familial Parkinson's disease
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DOI：
10.1016/s0140-6736(04)17103-1
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发表时间：
2004-09-25
期刊：
影响因子：
168.9
通讯作者：
Destée, A
中科院分区：
文献类型：
--
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
α-突触核蛋白基因的基因组三倍体(SNCA)已被报道导致遗传性早发性帕金森病合并痴呆。这些发现促使我们在9个帕金森病分离为常染色体显性特征的家系中筛查SNCA基因座的倍增。1个家系经半定量聚合酶链式反应鉴定为SNCA复制，外周血细胞荧光原位杂交分析证实。与SNCA三重家系相比，SNCA重复的临床表型与特发性帕金森病非常相似，发病年龄较晚，进展缓慢，认知能力下降和痴呆均不突出。这些发现表明SNCA基因剂量与疾病进展有直接关系。
Genomic triplication of the alpha-synuclein gene (SNCA) has been reported to cause hereditary early-onset parkinsonism with dementia. These findings prompted us to screen for multiplication of the SNCA locus in nine families in whom parkinsonism segregates as an autosomal dominant trait. One kindred was identified with SNCA duplication by semiquantitative PCR and confirmed by fluorescent in-situ hybridisation analysis in peripheral leucocytes. By contrast with SNCA triplication families, the clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent. These findings suggest a direct relation between SNCA gene dosage and disease progression.