Frequency of the LRRK2 G2019S mutation in South African patients with Parkinson’s disease
G2019S in LRRK2 is the most common mutation associated with Parkinson’s disease (PD). Highest frequencies are in North African Arabic (30–41%) and Ashkenazi Jewish (6–30%) populations, mostly due to founder effects. Here, we investigated the frequency of G2019S in 647 unrelated South African PD patients from different ancestral origins. It was found in only 1.2% (8/647) of patients. Notably, none of the 91 individuals of African ancestry had G2019S. It was present in 1.9% (3/154) and 1% (5/493) of early- and late-onset cases, respectively. The frequency of G2019S exhibits ethnic-specific differences and warrants further study in sub-Saharan African populations.
KeywordsParkinson’s disease LRRK2 gene G2019S mutation Phenotype South African patients
We thank the patients and their families for their participation in and contribution to this study. We also gratefully acknowledge the Western Province Blood Transfusion Service for providing the control samples.
This study received support from the National Research Foundation of South Africa (Grant Number: 106052) and the South African Medical Research Council (Self-Initiated Research Grant). We also acknowledge the support of the NRF-DST Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The Health Research Ethics Committee at Stellenbosch University (Protocol 2002/C059) approved this study. All procedures performed on human participants were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki declaration and its later amendments.
- 4.West AB, Moore DJ, Choi C, Andrabi SA, Li X, Dikeman D, Biskup S, Zhang Z, Lim KL, Dawson VL, Dawson TM (2007) Parkinson’s disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum Mol Genet 16:223–232. https://doi.org/10.1093/hmg/ddl471 CrossRefGoogle Scholar
- 8.Lesage S, Patin E, Condroyer C, Leutenegger AL, Lohmann E, Giladi N, Bar-Shira A, Belarbi S, Hecham N, Pollak P, Ouvrard-Hernandez AM, Bardien S, Carr J, Benhassine T, Tomiyama H, Pirkevi C, Hamadouche T, Cazeneuve C, Basak AN, Hattori N, Dürr A, Tazir M, Orr-Urtreger A, Quintana-Murci L, Brice A, for the French Parkinson's Disease Genetics Study Group, Agid Y, Bonnet AM, Borg M, Brice A, Broussolle E, Damier P, Destée A, Dürr A, Durif F, Lohmann E, Martinez M, Penet C, Pollak P, Rascol O, Tison F, Tranchant C, Troiano A, Vérin M, Viallet F, Vidailhet M (2010) Parkinson’s disease-related LRRK2 G2019S mutation results from independent mutational events in humans. Hum Mol Genet 19:1998–2004. https://doi.org/10.1093/hmg/ddq081 CrossRefGoogle Scholar
- 12.Hall T (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for windows 95/98/NT. Nucleic Acids Symposium Series, 41, 95–98. http://brownlab.mbio.ncsu.edu/JWB/papers/1999Hall1.pdf. Accessed 19 August 2019
- 13.Newman A, Evans NJ, Smith JG IS (2006) Jewish migration to South Africa: the records of the poor Jews’ temporary shelter. Isaac and Jessie Kaplan Centre for Jewish Studies and Research, University of Cape Town, Cape TownGoogle Scholar
- 14.Evans RJ (2006) The third Reich in power, 1933–1939. Penguin Press, New YorkGoogle Scholar
- 17.Alcalay RN, Mirelman A, Saunders-Pullman R, Tang MX, Mejia Santana H, Raymond D, Roos E, Orbe-Reilly M, Gurevich T, Bar Shira A, Gana Weisz M, Yasinovsky K, Zalis M, Thaler A, Deik A, Barrett MJ, Cabassa J, Groves M, Hunt AL, Lubarr N, San Luciano M, Miravite J, Palmese C, Sachdev R, Sarva H, Severt L, Shanker V, Swan MC, Soto-Valencia J, Johannes B, Ortega R, Fahn S, Cote L, Waters C, Mazzoni P, Ford B, Louis E, Levy O, Rosado L, Ruiz D, Dorovski T, Pauciulo M, Nichols W, Orr-Urtreger A, Ozelius L, Clark L, Giladi N, Bressman S, Marder KS (2013) Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord 28:1966–1971. https://doi.org/10.1002/mds.25647 CrossRefGoogle Scholar
- 18.Mirelman A, Heman T, Yasinovsky K, Thaler A, Gurevich T, Marder K, Bressman S, Bar-Shira A, Orr-Urtreger A, Giladi N, Hausdorff JM, on behalf of the LRRK2 Ashkenazi Jewish Consortium (2013) Fall risk and gait in Parkinson’s disease: the role of the LRRK2 G2019S mutation. Mov Disord 28:1683–1690. https://doi.org/10.1002/mds.25587 CrossRefGoogle Scholar
- 20.Okubadejo NU, Rizig M, Ojo OO et al (2018) Leucine rich repeat kinase 2 (LRRK2) Gly2019Ser mutation is absent in a second cohort of Nigerian Africans with Parkinson disease. PLoS One 363945. https://doi.org/10.1101/363945
- 21.Statistics South Africa (2011) Statistical release (revised) - census (2011). 78. Accessed 19 August 2019Google Scholar
- 22.Statistics South Africa (2016) Community Survey 2016 Statistical Release. Stats SA Stat South Africa Community Survey 2016 Results. https://doi.org/10.1017/CBO9781107415324.004. Accessed 19 August 2019