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LRRK2 Exon 41 Mutations in Sporadic Parkinson Disease in Europeans
Suzanne Lesage, PhD;
Sabine Janin;
Ebba Lohmann, MD;
Anne-Louise Leutenegger, PhD;
Laurence Leclere;
François Viallet, MD;
Pierre Pollak, MD;
Franck Durif, MD;
Stéphane Thobois, MD;
Valérie Layet, MD;
Marie Vidailhet, MD;
Yves Agid, MD, PhD;
Alexandra Dürr, MD, PhD;
Alexis Brice, MD; for the French Parkinson's Disease Genetics Study Group
Arch Neurol. 2007;64(3):425-430.
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.
Author Affiliations: 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 (Drs Lesage, Lohmann, Leutenegger, Vidailhet, Agid, Dürr, and Brice, Mss Janin, and Leclere), Département de Génétique, Cytogénétique et Embryologie (Drs Dürr and Brice), and Fédération des Maladies du Système Nerveux (Drs Agid and Brice), Centre Hospitalier Universitaire de la Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris; and Service de Neurologie, Hôpital Saint-Antoine (Dr Vidailhet); Paris; Service de Neurologie, Centre Hospitalier du Pays d’Aix, Aix-en-Provence (Dr Viallet); Département de Neurologie, Centre Hospitalier Universitaire de Grenoble, Grenoble (Dr Pollak); Service de Neurologie, Hôpital Gabriel Montpied, Clermont-Ferrand (Dr Durif); Service de Neurologie D, Hôpital Pierre Wertheimer, Lyon (Dr Thobois); and Unité de Cytogénétique et Génétique Médicale, Hôpital Gustave Flaubert, Le Havre (Dr Layet); France.
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