α-Synuclein gene duplication is present in sporadic Parkinson disease
α-Synuclein gene duplication is present in sporadic Parkinson disease
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DOI：
10.1212/01.wnl.0000271080.53272.c7
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发表时间：
2008-01-01
期刊：
影响因子：
9.9
通讯作者：
Jeon, B. S.
中科院分区：
文献类型：
--
作者：
Ahn, T. -B.;Kim, S. Y.;Jeon, B. S.
目的：家族性帕金森病(PD)患者存在α-突触核蛋白基因(SNCA)的增殖。方法：采用多重聚合酶链式反应对1106例帕金森病患者(PD=906，MSA=200)进行SNCA倍增检测。荧光原位杂交证实细胞增殖。[123垂直条]对SNCA倍增患者及其家属进行N-欧米伽-氟丙基-2-β-甲氧基-3-β-(4-碘苯基)-托烷([123垂直条]FP-CIT)SPECT。一名患者有阳性家族史，两名患者为散发性。每个患者的家人都有无症状的携带者。家族性帕金森病起病早，病程进展快，认知功能障碍，自主神经功能障碍。散发性帕金森病较为典型。([123竖条]FP-CIT)SPECT在患者中异常，在无症状携带者中正常。结论：散发性帕金森病(PD)存在SNCA倍增，需要进行筛查。无症状携带者的低外显率、临床异质性和正常的多巴胺转运体成像可能表明存在其他遗传修饰因素或环境触发因素，这些因素在SNCA重复导致的帕金森病的发病机制中发挥作用。
Objective: alpha-Synuclein gene ( SNCA) multiplication was found in familial Parkinson disease (PD). We examined SNCA multiplication in patients with familial and sporadic PD and multiple system atrophy (MSA).Methods: We screened 1,106 patients with parkinsonism (PD = 906, MSA = 200) for SNCA multiplication by multiplex PCR. Fluorescent in situ hybridization was done to confirm the multiplication. [123 vertical bar] N-omega-Fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-tropane ([123 vertical bar] FP- CIT) SPECT was done in the patients with SNCA multiplication and their family members.Results: Three patients were identified as having SNCA duplication. One patient had a positive family history, and two patients were sporadic. Each patient had asymptomatic carriers in their families. The familial case had early onset parkinsonism with rapidly progressive course, cognitive impairment, and dysautonomia. Sporadic cases were more typical of PD. ([123 vertical bar] FP-CIT) SPECT was abnormal in the patients and normal in the asymptomatic carriers.Conclusion: SNCA multiplication is present in sporadic Parkinson disease (PD) and needs to be screened. Low penetrance, clinical heterogeneity, and normal dopamine transporter imaging in asymptomatic carriers may suggest the presence of other genetic modifiers or environmental triggers that play a role in the pathogenesis of PD due to SNCA duplication.