title: LRRK2 G2019S mutation: frequency and haplotype data in South African Parkinson's disease patients.
abstract: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most significant genetic cause of Parkinson's disease (PD). The exact function of LRRK2 is currently unknown but the presence of multiple protein interaction domains including WD40 and ankyrin indicates that it may act a scaffold for assembly of a multi-protein signaling complex. The G2019S mutation in LRRK2 represents the most clinically relevant PD-causing mutation and has been found in both familial and sporadic forms of the disorder. This mutation is situated in the highly conserved kinase MAPKKK domain, and has been found in up to 40% of PD patients from North African Arabic, 30% of Ashkenazi Jewish and approximately 10% of Portuguese and Spanish populations. Although extensively investigated in numerous European and North American populations, studies on the frequency of G2019S in African countries have been rare. The present study is the first on the South African population. High-resolution melt analysis was used to identify the G2019S mutation and it was found in 2% (4/205) of the patients studied. G2019S was not found in any of the Black PD patients screened. In all four G2019S-positive probands the mutation was shown to be present on the common haplotype referred to as haplotype 1. This reveals that the four South African G2019S-positive probands (three Caucasian and one of mixed ancestry) share a common ancestor with the other haplotype 1-associated families reported worldwide.
authors.affiliation: Division of Molecular Biology and Human Genetics, University of Stellenbosch, 4th Floor Fisan Building, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa. sbardien@sun.ac.za
authors.forename: Soraya
authors.initials: S
authors.lastname: Bardien
authors.forename: Angelica
authors.initials: A
authors.lastname: Marsberg
authors.forename: Rowena
authors.initials: R
authors.lastname: Keyser
authors.forename: Debbie
authors.initials: D
authors.lastname: Lombard
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lesage
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013019:South Africa; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases