对坎帕尼亚地区帕金森病患者进行LRRK2基因R1441C和G2019S突变的基因筛查。

Genetic screening for the LRRK2 R1441C and G2019S mutations in Parkinsonian patients from Campania.

作者信息

De Rosa Anna, De Michele Giuseppe, Guacci Anna, Carbone Rosa, Lieto Maria, Peluso Silvio, Picillo Marina, Barone Paolo, Salemi Fabrizio, Laiso Antonio, Saccà Francesco, Tessitore Alessandro, Pellecchia Maria Teresa, Bonifati Vincenzo, Criscuolo Chiara

机构信息

Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Center for Neurodegenerative Diseases, University of Salerno, Italy.

出版信息

J Parkinsons Dis. 2014;4(1):123-8. doi: 10.3233/JPD-130312.

DOI:10.3233/JPD-130312

PMID:24496098

Abstract

BACKGROUND

PARK8 is the most common known mendelian form of Parkinson's Disease (PD). It is due to mutations in the leucine-rich repeat kinase 2 (LRRK2) gene and G2019S is considered the most frequent mutation in the Caucasian population, in particular in the Southern Europe and Mediterranean countries.

OBJECTIVE

We assessed the frequency of the G2019S and R1441C/H/G mutations in 513 (311 M and 202 F) unrelated PD patients from Campania, in Southern Italy.

METHODS

Three hundreds and thirty-six patients presented a sporadic disease, and 177 had a familial history of PD or tremor. Three hundreds and eighty cases originated from the province of Naples. We compared our LRRK2 mutation carriers to idiopathic PD patients matched for recruiting center, gender, age and age at onset.

RESULTS

Thirteen patients (8 M and 5 F) carried the R1441C mutation and 4 (3 M and 1 F) the G2019S mutation, all in heterozygous state. All carriers originated from the province of Naples. No carriers of the R1441H or R1441G mutations were found. The LRRK2 mutation carriers were clinically similar to idiopathic PD patients. The R1441C and G2019S mutations are not rare causes of PD in Campania, especially in the province of Naples and among the familial cases, where the overall mutation prevalence is 6.8%.

CONCLUSIONS

The R1441C prevalence was higher than that of G2019S (2.5% vs 0.8%), underlining the importance of the geographical differencies in LRRK2 mutation frequency for molecular screening and genetic counseling of PD patients.

摘要

背景

PARK8是帕金森病（PD）最常见的已知孟德尔遗传形式。它是由富含亮氨酸重复激酶2（LRRK2）基因突变引起的，G2019S被认为是白种人群中最常见的突变，尤其是在南欧和地中海国家。

目的

我们评估了来自意大利南部坎帕尼亚的513例（311例男性和202例女性）无亲缘关系的PD患者中G2019S和R1441C/H/G突变的频率。

方法

336例患者患有散发性疾病，177例有PD或震颤家族史。380例患者来自那不勒斯省。我们将LRRK2突变携带者与在招募中心、性别、年龄和发病年龄相匹配的特发性PD患者进行了比较。

结果

13例患者（8例男性和5例女性）携带R1441C突变，4例（3例男性和1例女性）携带G2019S突变，均为杂合状态。所有携带者均来自那不勒斯省。未发现R1441H或R1441G突变携带者。LRRK2突变携带者在临床上与特发性PD患者相似。R1441C和G2019S突变在坎帕尼亚是PD的常见病因，尤其是在那不勒斯省和家族性病例中，总体突变患病率为6.8%。