Complex relationship between parkin mutations and Parkinson disease
Complex relationship between parkin mutations and Parkinson disease
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DOI：
10.1002/ajmg.10525
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发表时间：
2002-07-08
期刊：
影响因子：
--
通讯作者：
Farrer, M
中科院分区：
文献类型：
--
作者：
West, A;Periquet, M;Farrer, M
帕金基因突变会导致青少年和早发性帕金森症。虽然帕金相关疾病被认为是一种常染色体隐性遗传病，但据报道，只有一个帕金等位基因发生突变，这增加了显性效应的可能性。在本报告中，我们重新评估了二十个杂合病例，并将突变筛选范围扩大到包括启动子和内含子/外显子边界。描述了新的缺失、点和内含子剪接位点突变以及启动子变异。这些数据加上对已发表的 Parkin 突变的完整回顾，证实 Parkin 的隐性缺失不仅是青少年和早发性帕金森症的危险因素，而且在某些情况下 Parkin 单倍体不足可能足以导致疾病。 (C) 2002 Wiley-Liss, Inc.
Mutations in the Parkin gene cause juvenile and early onset Parkinsonism. While Parkin-related disease is presumed to be an autosomal-recessive disorder, cases have been reported where only a single Parkin allele is mutated and raise the possibility of a dominant effect. In this report, we reevaluate twenty heterozygous cases and extend the mutation screening to include the promoter and intron/exon boundaries. Novel deletion, point and intronic splice site mutations are described, along with promoter variation. These data, coupled with a complete review of published Parkin mutations, confirms that not only is recessive loss of Parkin a risk factor for juvenile and early onset Parkinsonism but that Parkin haploinsufficiency may be sufficient for disease in some cases. (C) 2002 Wiley-Liss, Inc.