Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and The University of Sydney, St. Leonards, New South Wales, Australia.
Mov Disord. 2012 Sep 1;27(10):1299-303. doi: 10.1002/mds.25041. Epub 2012 Jul 17.
Mutations in parkin have been associated with autosomal recessive early-onset Parkinson's disease (PD). Here, we report on unusual phenotypic variability within a family with mutations in parkin.
The proband and her parents were clinically assessed. Mutation analysis was performed using genomic DNA and complementary DNA. The protein expression of Parkin and Mitofusin 2 was examined by western blotting.
The proband was a compound heterozygote with no detectable Parkin and presented with early-onset PD. The father, a single heterozygote with reduced expression of Parkin, had mild loss of arm swing. The mother, who had only very mild rigidity, was unexpectedly found to be a homozygote with no Parkin expression. The proband, but not the parents, met the Queen Square Brain Bank criteria for PD. Parkin-dependent ubiquitination of Mitofusin 2 was impaired in the mother and the proband.
We report the first case of a homozygous mutation carrier in parkin who had no functional protein and only mild signs of parkinsonism in her seventh decade, whereas her daughter developed typical early-onset PD. This family demonstrates phenotypic variability in parkin-related parkinsonism. © 2012 Movement Disorder Society.
Parkin 基因突变与常染色体隐性早发性帕金森病（PD）有关。在这里，我们报告了一个携带 Parkin 基因突变的家族中出现的不寻常表型变异性。
对先证者及其父母进行临床评估。使用基因组 DNA 和互补 DNA 进行突变分析。通过 Western blot 检查 Parkin 和 Mitofusin 2 的蛋白表达。
先证者是复合杂合子，Parkin 无法检测到，表现为早发性 PD。父亲是一个单杂合子，Parkin 表达减少，手臂摆动轻度丧失。母亲只有非常轻微的僵硬，出乎意料的是，她是一个没有 Parkin 表达的纯合子。先证者，但不是父母，符合 Queen Square Brain Bank 的 PD 标准。Parkin 依赖性 Mitofusin 2 的泛素化在母亲和先证者中受到损害。
我们报告了首例 Parkin 纯合子突变携带者的病例，她在 70 多岁时没有功能性蛋白，只有轻微的帕金森症状，而她的女儿则发展为典型的早发性 PD。这个家族表现出与 Parkin 相关的帕金森病的表型变异性。© 2012 运动障碍学会。
