title: Exonic rearrangements in the known Parkinson's disease-causing genes are a rare cause of the disease in South African patients.
abstract: Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. To date, a number of PD-causing genes have been found, including SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, ATP13A2, and most recently CHCHD2. Mutations in these genes range from point mutations to larger exonic rearrangements including deletions and duplications. This study aimed to detect possible copy number variation (CNV) in the known PD-causing genes in a cohort of South African patients with PD. Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed on a total of 210 South African PD patients, and possible CNVs were verified using quantitative real time PCR. No homozygous or compound heterozygous exon rearrangements in the genes analysed were found in the patient group. A heterozygous PARK2 exon 4 deletion was found in a sporadic patient with an age at onset of 51 years. Sanger sequencing did not reveal any additional mutations in PARK2 in this patient. Combining our results with that of previous studies in a South African cohort, the frequency of exonic rearrangements in the known PD-causing genes is only 1.8% (8/439 patients). In conclusion, CNV in the known PD-causing genes are a rare cause of PD in a South African cohort, and there may be as yet unknown genetic causes of PD that are specific to patients of African ethnicity.
authors.affiliation: Division of Molecular Biology & Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: celiavdm@sun.ac.za.
authors.forename: Celia
authors.initials: C
authors.lastname: van der Merwe
authors.affiliation: Division of Neurology, Tygerberg Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carr
authors.affiliation: Division of Molecular Biology & Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Glanzmann
authors.affiliation: Division of Molecular Biology & Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: sbardien@sun.ac.za.
authors.forename: Soraya
authors.initials: S
authors.lastname: Bardien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D018628:Gene Dosage; D015321:Gene Rearrangement; D006801:Humans; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D013019:South Africa; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Copy number variation; MLPA; PARK2; Parkinson’s disease; South African