Four Copies of SNCA Responsible for Autosomal Dominant Parkinson's Disease in Two Italian Siblings.
Four Copies of SNCA Responsible for Autosomal Dominant Parkinson's Disease in Two Italian Siblings.
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在两个意大利兄弟姐妹中，SNCA的四本负责常染色体显性帕金森氏病。
DOI：
10.1155/2015/546462
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Gambardella S
中科院分区：
文献类型：
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作者：
Ferese R;Modugno N;Campopiano R;Santilli M;Zampatti S;Giardina E;Nardone A;Postorivo D;Fornai F;Novelli G;Romoli E;Ruggieri S;Gambardella S
背景帕金森病（PD）的主要特征是α-突触核蛋白（SNCA）聚集和黑质纹状体含多巴胺神经元的丢失。在这项研究中，一种新的SNCA倍增被描述在两个兄弟姐妹的严重帕金森症的影响，具有早发性运动障碍，精神症状，认知功能减退。方法.使用高密度比较基因组杂交阵列（CGH-阵列）、多重连接依赖性探针扩增（MLPA）和定量PCR（qPCR）进行SNCA给药。基因分析与临床评价相关。结果同胞的遗传分析首次显示了一个351 Kb的三倍体，该三倍体含有SNCA基因沿着MMRN 1基因的6个外显子在4q22.1中，并且在该三倍体侧翼的基因组区域中重复了1.29 Mb。结论.该家族的鉴定表明SNCA基因倍增的一种新机制，证实了该区域的基因组不稳定性，并提供了PD患者基因型-表型相关性的数据。
Background. Parkinson's disease (PD) is mostly characterized by alpha-synuclein (SNCA) aggregation and loss of nigrostriatal dopamine-containing neurons. In this study a novel SNCA multiplication is described in two siblings affected by severe parkinsonism featuring early onset dyskinesia, psychiatric symptoms, and cognitive deterioration. Methods. SNCA dosage was performed using High-Density Comparative Genomic Hybridization Array (CGH-Array), Multiple Ligation Dependent Probe Amplification (MLPA), and Quantitative PCR (qPCR). Genetic analysis was associated with clinical evaluation. Results. Genetic analysis of siblings showed for the first time a 351 Kb triplication containing SNCA gene along with 6 exons of MMRN1 gene in 4q22.1 and a duplication of 1,29 Mb of a genomic region flanking the triplication. Conclusions. The identification of this family indicates a novel mechanism of SNCA gene multiplication, which confirms the genomic instability in this region and provides data on the genotype-phenotype correlation in PD patients.