PARK2 mutations and clinical features in a Chinese population with early-onset Parkinson's disease
PARK2 mutations and clinical features in a Chinese population with early-onset Parkinson's disease
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DOI：
10.1007/s00702-007-0011-6
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发表时间：
2008-05-01
影响因子：
3.3
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Chan, Daniel Kam Yin;Mok, Vincent;Hattori, Nobutaka
我们的目的是描述香港华人早发性帕金森病的PARK2突变和临床特征。研究对象从两家大医院招募。详细数据包括人口统计、发病年龄、疾病持续时间、神经系统表现、并发症和疾病严重程度。对PARK2突变进行遗传分析。招募34例患者（平均发病年龄= 39岁，平均病程= 10年）。7名患者报告有家族史。主要临床表现为静息性震颤（33/34）、运动迟缓（33/34）、僵直（30/34）、体位不稳（20/34）、左旋多巴反应良好（33/34）、发病不对称（31/34）、睡眠改善（12/34）。运动并发症在很多患者中都有报道，而抑郁是最常见的非运动并发症。5例患者被确定有PARK2突变。两个姐妹是一个插入和一个缺失的复合杂合子，一个新的和罕见的1 bp插入/无义突变c1378_1379insG（12外显子）和7外显子的完全缺失。另一位患者是纯合子，因为6号外显子完全缺失。鉴定出两个携带者，一个在12号外显子上有T1321C （Cys441Arg）错义突变，另一个在4号内含子上有一个snp。我们的研究回顾了中国人中PARK2突变的发生率高于之前的文献。两姐妹在发病年龄和表型表现上存在显著差异的复合杂合突变表明，该家族可能存在修饰因子的影响。
Our aim was to characterise PARK2 mutations and clinical features in Hong Kong Chinese with early-onset Parkinson's disease. Subjects were recruited from two major hospitals. Detailed data included demographics, age of onset, duration of disease, neurological manifestations, complications and disease severity. Genetic analysis for PARK2 mutations was performed. Thirty-four patients were recruited (mean age of onset = 39 years; mean duration of disease = 10 years). Seven patients reported a family history. The salient clinical manifestations were resting tremor (33/34), bradykinesia (33/34), rigidity (30/34), postural instability (20/34), good response to L-dopa (33/34), asymmetry at onset (31/34) and sleep benefit (12/34). Motor complications were reported in a significant number of patients, and depression was the most common nonmotor complication. Five patients were identified to have PARK2 mutations. Two sisters were compound heterozygotes for an insertion and a deletion, a novel and rare 1 bp insertion/nonsense mutation c1378_1379insG (exon 12) and the entire deletion of exon 7. Another patient was homozygous for the entire deletion of exon 6. Two carriers were identified, one with a T1321C (Cys441Arg) missense mutation in exon 12 and another with a snp within intron 4. Our study reviewed a higher prevalence of PARK2 mutations in Chinese than that previously documented. A compound heterozygous mutation within two sisters with significant differences in age of onset and phenotypic manifestations suggest that modifier affects may be present in this family.