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Analysis of exon dosage using MLPA in South African Parkinson's disease patients

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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 ≤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 α-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 α-synuclein in 8% of South African patients from different ethnic groups. One patient had a whole-gene triplication of α-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.

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Acknowledgments

We thank the study participants. Ms. Lindsey Adams is thanked for providing technical advice. This work was supported by the South African Medical Research Council, the Harry and Doris Crossley Foundation, and the University of Stellenbosch, South Africa.

Conflicts of interest

None declared.

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Authors and Affiliations

  1. Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, Cape Town, South Africa

    Rowena J. Keyser, Debbie Lombard & Soraya Bardien

  2. Division of Neurology, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa

    Debbie Lombard & Jonathan Carr

  3. Central Analytical Facility, University of Stellenbosch, Cape Town, South Africa

    Rene Veikondis

Authors
  1. Rowena J. Keyser
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  2. Debbie Lombard
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  3. Rene Veikondis
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  4. Jonathan Carr
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  5. Soraya Bardien
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Correspondence to Rowena J. Keyser.

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Keyser, R.J., Lombard, D., Veikondis, R. et al. Analysis of exon dosage using MLPA in South African Parkinson's disease patients. Neurogenetics 11, 305–312 (2010). https://doi.org/10.1007/s10048-009-0229-6

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  • DOI: https://doi.org/10.1007/s10048-009-0229-6

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