Centro per i Disordini del Movimento, Dipartimento di Scienze Cardiovascolari e Neurologiche, Sezione Neurologia, Università degli studi di Cagliari, Via Ospedale 46, 09124 Cagliari, Italy.
Parkinsons Dis. 2010 Aug 19;2010:537698. doi: 10.4061/2010/537698.
Mutations in LRRK2 represent the most common causes of Parkinson's disease (PD) identified to date, but their penetrance is incomplete and probably due to the presence of other genetic or environmental factors required for development of the disease. We analyzed the presence of parkin sequence variants (mutations or polymorphisms) and exon rearrangements in LRRK2 mutations carriers (both PD patients and unaffected relatives) in order to detect a possible modifier effect on penetrance. Eight families with nine PD patients with heterozygous LRRK2 mutations (identified within 380 Sardinian PD patients screened for the presence of the five most common LRRK2 mutations) and sixteen additional relatives were genetically investigated for the presence of LRRK2 and parkin mutations. No evidence was found for the presence of pathological parkin mutations or exon rearrangements in patients or not affected family members. Three single-nucleotide polymorphisms (SNPs) were identified both in patients and unaffected relatives but did not significantly differ between the two groups. These data provide no support to the hypothesis whereby such parkin gene mutations may be commonly implicated in possible effect on penetrance in LRRK2 mutation carriers.
LRRK2 突变是迄今为止发现的最常见的帕金森病 (PD) 病因，但它们的外显率并不完全，可能是由于其他遗传或环境因素的存在，这些因素是疾病发展所必需的。我们分析了 LRRK2 突变携带者（PD 患者和未受影响的亲属）中 parkin 序列变异（突变或多态性）和外显子重排的存在情况，以检测对外显率可能存在的修饰作用。在 380 名筛查五种最常见 LRRK2 突变的撒丁岛 PD 患者中，发现了九个杂合 LRRK2 突变的 PD 患者（确定了八位家族）和 16 名其他亲属，对他们进行了 LRRK2 和 parkin 突变的遗传研究。在患者或未受影响的家族成员中均未发现病理性 parkin 突变或外显子重排的证据。在患者和未受影响的亲属中均发现了三个单核苷酸多态性 (SNP)，但两组之间没有显著差异。这些数据不支持这样的假设，即这种 parkin 基因突变可能常见于 LRRK2 突变携带者的外显率的可能影响。
