title: Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients.
abstract: Parkinson disease (PD) is a chronic neurodegenerative movement disorder characterized by selective loss of nigrostriatal dopaminergic neurons and formation of Lewy bodies. Clinical manifestations include motor impairments involving tremor, bradykinesia, postural instability and rigidity. Using dHPLC method we screened exons 31, 35, 41, 48 of the Leucine-rich repeat kinase 2 (LRRK2) gene and exons 2, 6 and 7 of Parkinson protein 2 (parkin, PARK2) genes in a cohort of 216 consecutive, unrelated Slovak patients with familial or sporadic PD, including early and late onset. By this means we aimed to detect the most common pathogenic mutations within LRRK2 (Arg1441Cys, Arg1441Gly, Arg1628Pro, Tyr1699Cys, Gly2019Ser, Ile2020Thr, Gly2385Arg) and parkin genes responsible for late and early onset forms of disease, respectively. However, none of these mutations was identified in our cohort. Heterozygous point mutation p.Arg275Trp in exon 7 of parkin gene was identified in one patient with age at onset 61 years. Furthermore, we observed the presence of one exonic (LRRK2 ex 48: 7155A>G) and eight intronic polymorphisms (in LRRK2: IVS35+23T>A, IVS47-91insGCCAT, IVS47-91insGCAT, IVS47-41A>G, IVS47-9delT, IVS47-20C>T, IVS47-90A>G, in parkin: IVS2+25T>C), three of which were novel.
authors.affiliation: Department of Molecular Biology, Comenius University, Bratislava, Slovak Republic. bogeecs@gmail.com
authors.forename: Csaba
authors.initials: C
authors.lastname: Bognar
authors.forename: Marian
authors.initials: M
authors.lastname: Baldovic
authors.forename: Jan
authors.initials: J
authors.lastname: Benetin
authors.forename: Ludovit
authors.initials: L
authors.lastname: Kadasi
authors.forename: Andrea
authors.initials: A
authors.lastname: Zatkova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000208:ethnology* / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018154:Slovakia; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases