MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Mov Disord. 2012 Oct;27(12):1522-9. doi: 10.1002/mds.25132. Epub 2012 Sep 6.
Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) < 40 (9.5%), an affected first-degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from >5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity.
约 3.6%的帕金森病患者在 45 岁之前出现症状。早发性帕金森病（EOPD）患者的家族复发风险高于晚发性患者，已经描述了 3 种主要的隐性 EOPD 基因。我们旨在确定这些基因在英国队列和以前的研究中的突变患病率。我们筛选了一项高确定性区域性和社区为基础的患病率研究中的 136 名 EOPD 先证者，以寻找 PARK2（parkin）、PINK1、PARK7（DJ-1）和 LRRK2 外显子 41 中的致病性突变。我们还进行了系统评价，计算了以前报道的研究中病例的致病性突变比例。我们发现了 5 名携带致病性 PARK2 突变的患者、1 名携带 PINK1 突变的患者和 1 名携带 LRRK2 突变的患者。总体突变率为 5.1%。突变在发病年龄（AAO）<40 岁（9.5%）、一级亲属受累（6.9%）、同胞受累（28.6%）或父母近亲结婚（50%）的患者中更为常见。在我们的研究中，EOPD 突变携带者更有可能出现僵硬和肌张力障碍，并且 7 名突变携带者中有 6 名在发病时出现下肢症状。我们的系统评价包括来自 >5800 个独特病例的信息。总体而言，PARK2（parkin）、PINK1 和 PARK7（DJ-1）突变病例的加权平均比例分别为 8.6%、3.7%和 0.4%。PINK1 突变在亚洲人群中更为常见。已知 EOPD 基因的突变总体频率低于以前的估计。我们的研究表明，AAO 较低、有家族史或父母近亲结婚的患者更有可能发生突变。
