LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans |
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Authors: | Lesage Suzanne,Janin Sabine,Lohmann Ebba,Leutenegger Anne-Louise,Leclere Laurence,Viallet François,Pollak Pierre,Durif Franck,Thobois Stéphane,Layet Valérie,Vidailhet Marie,Agid Yves,Dürr Alexandra,Brice Alexis French Parkinson's Disease Genetics Study Group,Bonnet Anne-Marie,Borg Michel,Broussolle Emmanuel,Damier Philippe,Destée Alain,Martinez Maria,Penet Christiane,Rasco Olivier,Tison François,Tranchan Christine,Vérin Marc |
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Affiliation: | Institut National de la Santé et de la Recherche Médicale Unité 679, Neurology and Experimental Therapeutics, and Faculté de Médecine, Université Pierre et Marie Curie, 75651 Paris CEDEX 13, France. |
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Abstract: | BACKGROUND: Mutations in leucine-rich repeat kinase 2 gene (LRRK2), particularly the G2019S mutation in exon 41, have been detected in familial and sporadic Parkinson disease (PD) cases. OBJECTIVES: To assess the frequency of LRRK2 exon 41 mutations in a series of sporadic PD cases from Europe and to determine the clinical features of LRRK2 mutation carriers. DESIGN: We analyzed European cases of sporadic PD for the presence of LRRK2 exon 41 mutations. These mutations were screened by denaturing high-performance liquid chromatography, and abnormal chromatograph traces were investigated by direct sequencing to determine the exact nature of the variants. Early-onset sporadic PD cases were also screened for parkin mutations. The haplotypes associated with the G2019S mutation were determined. The clinical characteristics of patients carrying LRRK2 mutations were detailed. SETTING: French Network for the Study of Parkinson Disease Genetics. Patients Three hundred twenty patients with apparently sporadic PD from Europe. MAIN OUTCOME MEASURES: Results of genetic analyses. RESULTS: We found the G2019S mutation in 6 patients and identified 2 new variants (Y2006H and T2031S) in 1 patient each. Their clinical features were similar to those of typical PD. All G2019S mutation carriers shared a common haplotype. CONCLUSIONS: The G2019S mutation is almost as frequent in sporadic cases (1.9%) as in previously reported familial cases (2.9%) in Europe and occurs in the same common founder. We identified 2 novel variants. Although the phenotype of LRRK2 mutation carriers closely resembles that of typical PD, the age at onset was younger (29 years in 1 patient) than previously described, and 3 patients were improved by deep brain stimulation. |
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