LRRK2 mutations in Spanish patients with Parkinson disease -: Frequency, clinical features, and incomplete penetrance
LRRK2 mutations in Spanish patients with Parkinson disease -: Frequency, clinical features, and incomplete penetrance
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DOI：
10.1001/archneur.63.3.377
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发表时间：
2006-03-01
影响因子：
--
通讯作者：
Tolosa, E
中科院分区：
文献类型：
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作者：
Gaig, C;Ezquerra, M;Tolosa, E
背景：LRRK 2基因的几种致病性突变与家族性和散发性帕金森病（PD）病例有关。R144.1G突变在西班牙巴斯克地区的PD患者中较为常见，G2019 S突变是世界范围内多个人群中常见的突变。目的：确定LRRK 2 G2019 S和R1 441 G突变在西班牙非巴斯克地区的PD患者中的频率设计：我们筛选患者的LRRK 2 R1441 G和G2019 S突变的存在。通过限制性内切酶消化检测这些LRRK 2突变，并对具有异常电泳模式的样品进行测序以确定确切的核苷酸变化。详细研究了LRRK 2突变患者的临床特征和家族史。地点：西班牙东北部地区。患者：302例PDMAin患者结局指标：发病年龄、临床特征以及PD和LRRK 2突变的家族史。结果：R1441 G突变占PD总病例的0.7%。G2019 S突变在6.4%的家族性和3.4%的散发性病例中发现。此外，我们还发现了1例R1441 C突变患者。发病年龄范围为33 - 78岁。临床特征与经典PD没有不同，除了1例患者表现为持续8年的单一症状性腿静息震颤。此外，一个91岁的患者与G2019 S突变的未受影响的相对被发现是一个突变carrier.Conclusions：从西班牙东北部的PD患者的G2019 S突变频率是类似的报告在其他欧洲地区。R1441 G突变在加泰罗尼亚非常罕见。老年未受影响的G2019 S突变携带者的存在支持了先前描述的LRRK 2突变PD患者中不完全突变的发生。
Background: Several pathogenic mutations in the LRRK2 gene have been implicated in familial and sporadic cases of Parkinson disease (PD). The R144.1G mutation is frequent in Spanish patients of Basque ethnicity with PD, and the G2019S mutation is a common mutation found in several populations worldwide.Objectives: To determine the frequency of the LRRK2 G2019S and R1 441 G mutations in PD patients from the non-Basque northeast region of Spain (Catalonia), and to characterize their family history and clinical features.Design: We screened patients for the presence of the LRRK2 R1441G and G2019S mutations. These LRRK2 mutations were detected by restriction endonuclease digestion, and samples with an abnormal electrophoresis pattern were sequenced to identify the exact nucleotide change. The clinical features and family history of patients with LRRK2 mutations were studied in detail.Setting: The northeast region of Spain.Patients: Three hundred two patients with PDMain Outcome Measures: Onset age, clinical features, and family history of PD and LRRK2 mutations.Results: The R1441G mutation was present in 0.7% of total PD cases. The G2019S mutation was found in 6.4% of familial and 3.4% of sporadic cases. Additionally, we found I patient with the R1441 C mutation. Age at onset ranged from 33 to 78 years. Clinical features were not different from classic PD, except for I patient who presented with monosymptomatic leg rest tremor of 8 years' duration. In addition, a 91-year-old unaffected relative of a patient with the G2019S Mutation was found to be a mutation carrier.Conclusions: The G2019S mutation frequency in PD patients from northeast Spain is similar to that reported in other European regions. The R1441G mutation is very uncommon in Catalonia. The presence of an aged unaffected G2019S mutation carrier supports the previously described occurrence of incomplete penetrance in PD patients with LRRK2 mutations.