墨西哥裔早发性帕金森病患者中 Parkin 外显子重排的高频发生。

High frequency of Parkin exon rearrangements in Mexican-mestizo patients with early-onset Parkinson's disease.

机构信息

Neurogenetics Department, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico.

出版信息

Mov Disord. 2012 Jul;27(8):1047-51. doi: 10.1002/mds.25030. Epub 2012 Jul 6.

DOI:10.1002/mds.25030

PMID:22777964

Abstract

BACKGROUND

Parkin mutations in patients with early-onset Parkinson's disease (EOPD) are estimated to occur in 49% of familial cases and 18% of sporadic cases.

METHODS

We analyzed the entire sequence-coding region and dosage mutations of parkin in 63 Mexican-mestizo EOPD patients and 120 controls.

RESULTS

Parkin mutations were present in 34 patients (54.0%). Exon rearrangements, predominantly spanning exons 9 and 12 (31.7% and 19.0%, respectively) were present in 32 patients, with 17.5% carrying simple heterozygous and 25.4% carrying compound heterozygous parkin mutations.

CONCLUSIONS

A higher frequency of parkin exon rearrangements than of sequence mutations was observed. Patients with parkin exons 9 and 12 rearrangements showed a later age at onset than did cases with other regions affected (40.3 ± 4.5 vs 30.1 ± 8.8; P = .005), suggesting a mutational hot spot in the etiology of Mexican-mestizo patients with EOPD. To our knowledge, this study represents the largest sampling of Mexican-mestizo patients with EOPD cases for which parkin sequence and dosage alterations were analyzed. .

摘要

背景

早发性帕金森病（EOPD）患者中，Parkin 突变估计在家族性病例中占 49%，在散发性病例中占 18%。

方法

我们分析了 63 名墨西哥裔 EOPD 患者和 120 名对照者的 Parkin 全长编码区和剂量突变。

结果

34 名患者（54.0%）存在 Parkin 突变。32 名患者存在外显子重排，主要跨越外显子 9 和 12（分别为 31.7%和 19.0%），17.5%的患者携带单纯杂合性突变，25.4%的患者携带复合杂合性 Parkin 突变。

结论

与序列突变相比，Parkin 外显子重排的频率更高。携带 Parkin 外显子 9 和 12 重排的患者发病年龄晚于其他受影响区域的病例（40.3±4.5 岁 vs. 30.1±8.8 岁；P=0.005），提示在墨西哥裔 EOPD 患者病因中存在突变热点。据我们所知，这项研究是针对 Parkin 序列和剂量改变进行分析的最大规模的墨西哥裔 EOPD 患者抽样研究。