title: LRRK2 mutations in patients with Parkinson's disease from Peru and Uruguay.
abstract: Variation in the leucine-rich repeat kinase 2 (LRRK2) gene represents the most common genetic determinant of Parkinson's disease (PD) identified to date. While the frequency and distribution of LRRK2 mutations have been well-studied in Europe and North America, few data are available from South America. To address this gap in knowledge, we screened two cohorts of patients with PD from Peru (n=240) and Uruguay (n=125) for the three most common LRRK2 mutations (R1441C, R1441G, G2019S). We identified at total of seven patients with mutations, one with R1441G, and six with G2019S. The carrier frequency was significantly greater in the Uruguayan cohort (4.8%) than in the Peruvian cohort (0.4%; p=0.007). This likely resulted from a greater admixture proportion in the Peruvian sample. Haplotype analyses suggested that G2019S was probably brought to Peru and Uruguay by European settlers. In contrast, the origin of R1441G in our cohort was not clear, as the patient with this mutation had a background haplotype that was clearly distinct from that reported in carriers from Europe and North America. Our data add to a growing body of evidence indicating that LRRK2 mutations are widely distributed across South America but might differ by region in prevalence.
authors.affiliation: Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USA.
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Carlos
authors.initials: C
authors.lastname: Cosentino
authors.forename: Victoria
authors.initials: V
authors.lastname: Marca
authors.forename: Luis
authors.initials: L
authors.lastname: Torres
authors.forename: Pilar
authors.initials: P
authors.lastname: Mazzetti
authors.forename: Olimpio
authors.initials: O
authors.lastname: Ortega
authors.forename: Victor
authors.initials: V
authors.lastname: Raggio
authors.forename: Ruth
authors.initials: R
authors.lastname: Aljanati
authors.forename: Ricardo
authors.initials: R
authors.lastname: Buzó
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.forename: Elena
authors.initials: E
authors.lastname: Dieguez
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
mesh_terms: D019943:Amino Acid Substitution; D002353:Carrier State; D015331:Cohort Studies; D005190:Family; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008487:Medical History Taking; D010300:Parkinson Disease / Q000235:genetics*; D010568:Peru; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014583:Uruguay; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases