BACKGROUND: 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. OBJECTIVES: 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. 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 PD. MAIN 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 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. 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.
BACKGROUND: 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. OBJECTIVES: To determine the frequency of the LRRK2G2019S and R1441G mutations in PDpatients 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 LRRK2R1441G 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 PD. MAIN 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 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. CONCLUSIONS: The G2019S mutation frequency in PDpatients 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 PDpatients with LRRK2 mutations.
Authors: Carles Gaig; María José Martí; Mario Ezquerra; Maria Jesús Rey; Adriana Cardozo; Eduardo Tolosa Journal: J Neurol Neurosurg Psychiatry Date: 2007-01-08 Impact factor: 10.154
Authors: A S Chen-Plotkin; W Yuan; C Anderson; E McCarty Wood; H I Hurtig; C M Clark; B L Miller; V M-Y Lee; J Q Trojanowski; M Grossman; V M Van Deerlin Journal: Neurology Date: 2007-10-03 Impact factor: 9.910
Authors: K Haugarvoll; R Rademakers; J M Kachergus; K Nuytemans; O A Ross; J M Gibson; E-K Tan; C Gaig; E Tolosa; S Goldwurm; M Guidi; G Riboldazzi; L Brown; U Walter; R Benecke; D Berg; T Gasser; J Theuns; P Pals; P Cras; P Paul De Deyn; S Engelborghs; B Pickut; R J Uitti; T Foroud; W C Nichols; J Hagenah; C Klein; A Samii; C P Zabetian; V Bonifati; C Van Broeckhoven; M J Farrer; Z K Wszolek Journal: Neurology Date: 2008-03-12 Impact factor: 9.910
Authors: Carolina Perez-Pastene; Stephanie A Cobb; Fernando Díaz-Grez; Mary M Hulihan; Marcelo Miranda; Pablo Venegas; Osvaldo Trujillo Godoy; Jennifer M Kachergus; Owen A Ross; Luis Layson; Matthew J Farrer; Juan Segura-Aguilar Journal: Neurosci Lett Date: 2007-06-17 Impact factor: 3.046