Mutations in the PINK1 gene are the second most common cause after parkin of autosomal recessive early-onset Parkinson's disease (PD). PINK1 is a protein kinase that is localized to the mitochondrion and is ubiquitously expressed in the human brain. Recent studies aimed at elucidating the function of PINK1, have found that it has neuroprotective properties against mitochondrial dysfunction and proteasomally-induced apoptosis. In the present study, we aimed to investigate the prevalence of PINK1 genetic variants in 154 South African PD patients from all ethnic groups. Mutation screening was performed using the High-Resolution Melt technique and direct sequencing. A total of 16 sequence variants were identified: one known homozygous mutation (Y258X), two heterozygous missense variants (P305A and E476K), and 13 polymorphisms of which five were novel. No homozygous exonic deletions were detected. The novel P305A variant was found in a female patient of Black Xhosa ethnicity who has a positive family history of the disease and an age at onset of 30years. This variant has the potential to modulate enzymatic activity due to its location in the kinase domain. This is the first report on mutation screening of PINK1 in the South African population. Results from the present study showed that point mutations and homozygous exonic deletions in PINK1 are not a common cause of PD in the South African population.
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