title: Analysis of exon dosage using MLPA in South African Parkinson's disease patients.
abstract: Genomic rearrangements (exon dosage) are common mutations reported in Parkinson's disease (PD) patients. In the present study, we aimed to investigate the prevalence of genomic rearrangements in 88 South African patients with predominantly early-onset PD (age-at-onset <or=50 years). The multiplex ligation-dependent probe amplification method was used to detect exon dosage changes. Two commercially available probe kits, SALSA P051 and P052, were used and together the kits consisted of probes for exons of alpha-synuclein, parkin, PINK1, DJ-1, LRRK2, UCH-L1, ATP13A2, LPA, TNFRSF9, CAV2, CAV1, GCH1, and two-point mutations. We identified exonic rearrangements in parkin and alpha-synuclein in 8% of South African patients from different ethnic groups. One patient had a whole-gene triplication of alpha-synuclein; representing only the fourth family with this mutation reported to date. We found six patients with parkin mutations who had either heterozygous duplications and deletions, or homozygous deletions. A false positive result of an exonic deletion detected in one patient turned out to be homozygous point mutation (Y258X) in PINK1. No exonic rearrangements were found in four of the PD genes; LRRK2, PINK1, DJ-1, and ATP13A2. Mutations in parkin were the predominant genetic cause; however, the frequency of exon dosage in our study group is low compared with previous studies. This indicates the possible involvement of other as yet unidentified PD genes in the development of the disease in the South African population.
authors.affiliation: Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, Cape Town, South Africa. rowenak@sun.ac.za
authors.forename: Rowena J
authors.initials: RJ
authors.lastname: Keyser
authors.forename: Debbie
authors.initials: D
authors.lastname: Lombard
authors.forename: Rene
authors.initials: R
authors.lastname: Veikondis
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carr
authors.forename: Soraya
authors.initials: S
authors.lastname: Bardien
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D005091:Exons; D005260:Female; D018628:Gene Dosage; D015321:Gene Rearrangement; D020131:Genes, Duplicate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D015995:Prevalence; D017384:Sequence Deletion; D013019:South Africa / Q000453:epidemiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein