Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls
Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls
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DOI：
10.1136/jmg.2007.051854
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Brice, A.
中科院分区：
文献类型：
--
作者：
Lesage, S.;Lohmann, E.;Brice, A.
背景：parkin基因突变导致常染色体隐性遗传早发性帕金森综合征。帕金基因单个杂合突变的影响尚不清楚。本研究的目的是评估外显子parkin变异的频率在病例对照study.Methods：parkin基因的点突变和外显子重排筛选172例法国帕金森病（PD）患者和170名来自同一人群的控制。结果：共检测到10个外显子序列变异，包括3个已知的多态性和7个罕见的杂合子变异，其中2个为新发现。早发性PD患者（n = 10）的罕见杂合子变异显著多于对照组（n= 2）。PINK 1，DJ-1和LRRK 2外显子41的10例杂合子parkin筛选未能确定第二个致病突变。结论：这些结果表明，单一的parkin突变增加早发性PD的风险，但不能排除第二个parkin突变的可能性。
Background: Mutations in the parkin gene cause autosomal recessive early-onset parkinsonism. The effect of single heterozygous mutations in parkin is still unclear. The aim of this study was to evaluate the frequency of exonic parkin variants in a case-control study.Methods: The parkin gene was screened for both point mutations and exon rearrangements in 172 French patients with Parkinson disease (PD) and 170 controls from the same population. Patients with single parkin variants were also screened for PINK1, DJ-1 and LRRK2 exon 41 mutations.Results: 10 exonic sequence variations were identified, including 3 known polymorphisms and 7 rare heterozygous variants, 2 of which were novel. There were significantly more rare heterozygous variants in patients (n = 10) with early-onset PD than in controls (n= 2). Screening of PINK1, DJ-1 and LRRK2 exon 41 in the 10 patients heterozygous for parkin failed to identify a second causative mutation.Conclusion: These results suggest that single parkin mutations increase the risk of early-onset PD, but the possibility of a second parkin mutation cannot be excluded.