title: LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  French Network for the Study of Parkinson Disease Genetics. Patients Three hundred twenty patients with apparently sporadic PD from Europe.
  
  
  METHODS
  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.
authors.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.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lesage
authors.forename: Sabine
authors.initials: S
authors.lastname: Janin
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Leutenegger
authors.forename: Laurence
authors.initials: L
authors.lastname: Leclere
authors.forename: François
authors.initials: F
authors.lastname: Viallet
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.forename: Valérie
authors.initials: V
authors.lastname: Layet
authors.forename: Marie
authors.initials: M
authors.lastname: Vidailhet
authors.forename: Yves
authors.initials: Y
authors.lastname: Agid
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Borg
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.forename: Philippe
authors.initials: P
authors.lastname: Damier
authors.forename: Alain
authors.initials: A
authors.lastname: Destée
authors.forename: Maria
authors.initials: M
authors.lastname: Martinez
authors.forename: Christiane
authors.initials: C
authors.lastname: Penet
authors.forename: Olivier
authors.initials: O
authors.lastname: Rasco
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchan
authors.forename: Marc
authors.initials: M
authors.lastname: Vérin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D005060:Europe; D005091:Exons / Q000235:genetics*; D005260:Female; D006639:Histidine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
chemical_list: D013912:Threonine; D014443:Tyrosine; D012694:Serine; D006639:Histidine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases