title: Pathogenic Lrrk2 substitutions and Amyotrophic lateral sclerosis.
abstract: Pathogenic Lrrk2 Y1699C substitution observed in a large German-Canadian kindred presents a neurodegenerative disorder that is reminiscent of amyotrophic lateral sclerosis and Parkinsonism-Dementia Complex. We screened 54 patients with ALS for seven known Lrrk2 pathogenic substitutions in the Roc, COR and kinase domains. No mutations were observed suggesting that this locus does not have a major influence on the ALS phenotype. However we can not rule out other genetic variation at the LRRK2 locus may play a role in parkinsonian disorders with amyotrophic lateral sclerosis and may be considered candidates for genetic screening.
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Whittle
authors.forename: O A
authors.initials: OA
authors.lastname: Ross
authors.forename: A
authors.initials: A
authors.lastname: Naini
authors.forename: P
authors.initials: P
authors.lastname: Gordon
authors.forename: H
authors.initials: H
authors.lastname: Mistumoto
authors.forename: J C
authors.initials: JC
authors.lastname: Dächsel
authors.forename: J T
authors.initials: JT
authors.lastname: Stone
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: S
authors.initials: S
authors.lastname: Przedborski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D001483:Base Sequence / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases