俄罗斯帕金森病患者中LRRK2突变的筛查：一种新型LRRK2变异体的鉴定

Screening for LRRK2 mutations in patients with Parkinson's disease in Russia: identification of a novel LRRK2 variant.

作者信息

Pchelina S N, Yakimovskii A F, Emelyanov A K, Ivanova O N, Schwarzman A L, Singleton A B

机构信息

St. Petersburg State Pavlov Medical University, St. Petersburg, Russia.

出版信息

Eur J Neurol. 2008 Jul;15(7):692-6. doi: 10.1111/j.1468-1331.2008.02149.x. Epub 2008 Apr 24.

DOI:10.1111/j.1468-1331.2008.02149.x

PMID:18435766

Abstract

BACKGROUND AND PURPOSE

Mutations in LRRK2, encoding leucine-rich repeat kinase 2 (or Dardarin), cause autosomal dominant Parkinson's disease (AdPD) and are also found in sporadic PD (sPD). To investigate the frequency of LRRK2 mutations in a sample of Russian PD patients.

METHODS

We sequenced the complete coding region of LRRK2 in 65 patients with AdPD and in 30 patients with sPD. Furthermore, in 20 patients with AdPD and in 159 patients with sPD we screened several common LRRK2 mutations (G2019S, R1441C/G/H, I2012T and I2020T).

RESULTS

Five AdPD patients had the LRRK2 G2019S mutation (5.9%, 5/85). In addition, we discovered a novel LRRK2 variant V1613A in a family with a tremor dominant form of AdPD; this variant was not present in controls. We identified two patients with LRRK2 mutations in sPD: one with the G2019S mutation (0.5; 1/189) and another with the previously described R1441C mutation (0,5; 1/189).

CONCLUSIONS

LRRK2 mutations are common amongst patients with PD in Russia. The results also show that the G2019S mutation is the most frequent. We identified one novel mutation in a functional region of LRRK2.

摘要

背景与目的

富含亮氨酸重复激酶2（或帕金森病蛋白）编码基因LRRK2的突变会导致常染色体显性帕金森病（AdPD），也见于散发性帕金森病（sPD）。本研究旨在调查俄罗斯帕金森病患者样本中LRRK2突变的频率。

方法

我们对65例AdPD患者和30例sPD患者的LRRK2完整编码区进行了测序。此外，我们还对20例AdPD患者和159例sPD患者筛查了几种常见的LRRK2突变（G2019S、R1441C/G/H、I2012T和I2020T）。

结果

5例AdPD患者存在LRRK2 G2019S突变（5.9%，5/85）。此外，我们在一个震颤为主型AdPD家族中发现了一种新的LRRK2变异体V1613A；该变异体在对照组中不存在。我们在sPD患者中鉴定出2例LRRK2突变患者：1例为G2019S突变（0.5%；1/189），另1例为先前描述的R1441C突变（0.5%；1/189）。