Gaig Carles, Ezquerra Mario, Marti Maria Jose, Muñoz Esteban, Valldeoriola Francesc, Tolosa Eduardo
Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
Arch Neurol. 2006 Mar;63(3):377-82. doi: 10.1001/archneur.63.3.377.
Several pathogenic mutations in the LRRK2 gene have been implicated in familial and sporadic cases of Parkinson disease (PD). The R1441G mutation is frequent in Spanish patients of Basque ethnicity with PD, and the G2019S mutation is a common mutation found in several populations worldwide.
To determine the frequency of the LRRK2 G2019S and R1441G mutations in PD patients from the non-Basque northeast region of Spain (Catalonia), and to characterize their family history and clinical features.
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.
The northeast region of Spain. Patients Three hundred two patients with PD.
Onset age, clinical features, and family history of PD and LRRK2 mutations.
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 1 patient with the R1441C mutation. Age at onset ranged from 33 to 78 years. Clinical features were not different from classic PD, except for 1 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.
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.
LRRK2基因中的几种致病突变与帕金森病（PD）的家族性和散发性病例有关。R1441G突变在患有PD的巴斯克族西班牙患者中很常见，而G2019S突变是在全球多个群体中发现的常见突变。
确定西班牙非巴斯克东北地区（加泰罗尼亚）PD患者中LRRK2 G2019S和R1441G突变的频率，并描述其家族史和临床特征。
我们对患者进行LRRK2 R1441G和G2019S突变检测。通过限制性内切酶消化检测这些LRRK2突变，对电泳图谱异常的样本进行测序以确定确切的核苷酸变化。详细研究了LRRK2突变患者的临床特征和家族史。
西班牙东北地区。患者302例PD患者。
PD的发病年龄、临床特征以及LRRK2突变的家族史。
R1441G突变存在于0.7%的PD病例中。G2019S突变在6.4%的家族性病例和3.4%的散发性病例中被发现。此外，我们发现1例患者存在R1441C突变。发病年龄在33至78岁之间。临床特征与典型PD无异，只有1例患者出现了持续8年的单症状腿部静息性震颤。此外，发现1名携带G2019S突变患者的91岁未受影响的亲属也是突变携带者。
西班牙东北部PD患者中G2019S突变频率与其他欧洲地区报道的相似。R1441G突变在加泰罗尼亚非常罕见。老年未受影响的G2019S突变携带者的存在支持了先前描述的LRRK2突变的PD患者中存在不完全外显率的情况。
