Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease
Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease
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DOI：
10.1212/01.wnl.0000049470.00180.07
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发表时间：
2003-03-11
期刊：
影响因子：
9.9
通讯作者：
Nichols, WC
中科院分区：
文献类型：
--
作者：
Foroud, T;Uniacke, SK;Nichols, WC
背景：绝大多数先前发现的帕金突变都是在青少年或早发性PD患者中发现的。先前对晚发性帕金森病队列的筛查并没有发现大量的帕金突变。方法：确定至少有两个兄弟姐妹患有帕金森病的家庭，以确定与帕金森病易感性相关的基因。通过定量PCR和外显子测序，对那些患有早发性PD（发病年龄小于或等于50岁）或患有帕金基因7内含子标记物的lod评分阳性的家庭进行帕金基因筛选。结果：在47个家族的103个个体中共鉴定出25种不同的帕金基因突变。在41个个体中发现了两个帕金等位基因的突变，而在62个个体中只观察到两个帕金等位基因中的一个突变。35名帕金突变患者（34%）发病年龄在60岁或以上，其中30名（86%）仅在一个帕金等位基因上可检测到突变。在有两个、一个或没有突变的帕金基因拷贝的个体中，几乎没有观察到显著的临床差异。结论：帕金基因突变发生在发病年龄较大（大于或等于60岁）且有家族病史的PD患者中。此外，帕金森阳性个体的临床表现与没有突变的个体非常相似。
Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset less than or equal to50 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusions: Mutations in the parkin gene occur among individuals with PD with an older age at onset (greater than or equal to60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.