Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease.
Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease.
复制标题
DOI：
--
复制
发表时间：
2006
影响因子：
11.2
通讯作者：
K. Nishioka;Shin Hayashi;M. Farrer;A. Singleton;H. Yoshino;H. Imai;Toshiaki Kitami;Kenichi Sato;R. Kuroda;H. Tomiyama;K. Mizoguchi;M. Murata;T. Toda;I. Imoto;J. Inazawa;Y. Mizuno;N. Hattori
中科院分区：
文献类型：
--
作者：
K. Nishioka;Shin Hayashi;M. Farrer;A. Singleton;H. Yoshino;H. Imai;Toshiaki Kitami;Kenichi Sato;R. Kuroda;H. Tomiyama;K. Mizoguchi;M. Murata;T. Toda;I. Imoto;J. Inazawa;Y. Mizuno;N. Hattori
目的近年来，α-突触核蛋白基因(SNCA)的基因组倍增被报道为遗传性早发性帕金森综合征的致病基因。本研究的目的是评估常染色体显性遗传性帕金森病(ADPD)的SNCA倍增频率。方法应用定量聚合酶链式反应对113例ADPD先证者和200例散发性PD患者进行筛查，并用荧光原位杂交(FISH)和比较基因组杂交芯片证实SNCA扩增。结果在ADPD患者中发现2个SNCA重复的家系(A家系2例，B家系1例)。尽管他们有相同的SNCA重复，但有一名患者患有痴呆症。由于每个患者起源的区域之间存在完全相同的差异，这一发现表明SNCA增殖的表型也可能受到复制区域范围的影响。我们还在两名患者的家属中发现了无症状携带者。有趣的是，一个家系的外显率为33.3%(2/6)，这表明这一比例远远低于预期。这两个新发现的日本SNCA重复患者和5个先前发现的SNCA三重或重复突变的美国和欧洲家系表明，SNCA倍增的发生率可能比先前估计的更高。
OBJECTIVE Recently, genomic multiplications of alpha-synuclein gene (SNCA) have been reported to cause hereditary early-onset parkinsonism. The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD). METHODS We screened 113 ADPD probands and 200 sporadic PD cases by quantitative polymerase chain reaction and confirmed SNCA multiplications by fluorescence in situ hybridization (FISH) and comparative genomic hybridization array. RESULTS Two families (two patients from Family A and one from Family B) with SNCA duplication were identified among ADPD patients. Even though they had the same SNCA duplication, one patient had dementia. Because there was exactly the same difference between the regions originated from each patient, the finding suggests that the phenotype of SNCA multiplication may be also influenced by the range of duplication region. We also detected asymptomatic carriers in the families of both patients. Interestingly, the penetrance ratio was 33.3% (2/6) in one kindred, indicating that the ratio was very much lower than expected. INTERPRETATION These two newly identified Japanese patients with SNCA duplication and the five previously identified American and European families with SNCA triplication or duplication mutations indicate that the incidence of SNCA multiplication may be more frequent than previously estimated.