1. Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease
- Author
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Lesage, S, Condroyer, C, Lannuzel, A, Lohmann, E, Troiano, A, Tison, F, Damier, P, Thobois, S, Ouvrard-Hernandez, A-M, Rivaud-Péchoux, S, Brefel-Courbon, C, Destée, A, Tranchant, C, Romana, M, Leclere, L, Dürr, A, Brice, A, French Parkinson's Disease Genetics Study Group, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service de neurologie, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Clinique neurologique, Hôpital Laennec, Service de neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de neurochirurgie générale et stéréotaxique fonctionnelle, Hôpital Roger Salengro [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Pharmacogénétique et abords thérapeutiques des maladies héréditaires, Université des Antilles et de la Guyane (UAG)-Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université des Antilles et de la Guyane (UAG), French Parkinson's Disease Genetics Study Group, ANR-05-NEUR-0019,LRRK2 in PD,Pathologie moléculaire et modèles murins du gène LRRK2, impliqué dans la maladie de Parkinson(2005), Pollak, Pierre, Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Savasta, Marc, Neurosciences, neurologie et psychiatrie - Pathologie moléculaire et modèles murins du gène LRRK2, impliqué dans la maladie de Parkinson - - LRRK2 in PD2005 - ANR-05-NEUR-0019 - NEURO - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,Proband ,MESH: Chi-Square Distribution ,Parkinson's disease ,DNA Mutational Analysis ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,medicine.disease_cause ,Exon ,MESH: Aged, 80 and over ,0302 clinical medicine ,Gene Frequency ,European Continental Ancestry Group/genetics ,MESH: DNA Mutational Analysis ,Genetics (clinical) ,Aged, 80 and over ,MESH: Aged ,Genetics ,LRRK2 Gene ,0303 health sciences ,Mutation ,MESH: Middle Aged ,MESH: European Continental Ancestry Group ,Middle Aged ,LRRK2 ,Pedigree ,3. Good health ,Female ,Adult ,MESH: Mutation ,Adolescent ,MESH: Pedigree ,Protein-Serine-Threonine Kinases/genetics ,DNA Mutational Analysis/methods ,Black People ,Protein Serine-Threonine Kinases ,Parkinsonian Disorders/diagnosis/genetics ,Biology ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,White People ,MESH: Protein-Serine-Threonine Kinases ,03 medical and health sciences ,Parkinsonian Disorders ,MESH: Analysis of Variance ,MESH: Gene Frequency ,medicine ,Humans ,Gene ,Allele frequency ,Aged ,030304 developmental biology ,MESH: Adolescent ,Analysis of Variance ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Chi-Square Distribution ,MESH: Humans ,MESH: Parkinsonian Disorders ,African Continental Ancestry Group/genetics ,MESH: Adult ,medicine.disease ,MESH: Male ,ddc:616.8 ,nervous system diseases ,MESH: African Continental Ancestry Group ,MESH: Female ,030217 neurology & neurosurgery - Abstract
International audience; BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.
- Published
- 2009
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