Molecular analysis of the parkin gene in South African patients diagnosed with Parkinson's disease.

Parkinson's disease (PD) is a common movement disorder which may arise from mutations in the parkin gene. To date, more than 100 different parkin mutations have been reported. The aim of the present study was to determine the frequency of point mutations and homozygous exon deletions in the parkin gene in a group of 91 South African patients diagnosed with PD. Mutation screening of the 12 exons of parkin was performed using single strand conformation polymorphism analysis and the high-resolution melt technique. Six different mutations were identified: four putative disease-causing missense heterozygous changes (H200Q, D280N, E310D and R402C) and two homozygous exon deletions (exons 3 and 4, and exon 4). The D280N and R402C variants have both previously been described but their pathogenic status has been equivocal. In the present study, the D280N variant was observed in three early onset PD-affected siblings and was not present in a 63-year-old unaffected sibling. This data provide further support for the pathogenicity of this variant which is situated within the first RING finger of the RING-box. None of the four missense variants were detected in over 100 ethnic-matched control chromosomes. We conclude that point mutations and homozygous exon deletions in the parkin gene are not a major cause of PD in the South African population. Further studies on this group of patients are needed to determine the contribution of heterozygous exon deletions and insertions in parkin. The present study is the first report on the molecular etiology of PD in South African patients.