EDITORIAL

 

Genetic screening of South African families with Parkinson's disease

 

 

Parkinson's disease (PD) appears to be increasing exponentially throughout the world, including in populations in sub-Saharan Africa.^[1] The largest known risk factor for PD is increased age. Other risk factors include exposure to environmental factors (such as pesticides), male sex, a positive family history and genetic factors. ^[2,3] Over the past three decades, the discoveries of pathogenic variants in a large number of genes have highlighted a genetic component in about one in five people living with PD.^[4] These discoveries have led to important insights into the cellular mechanisms that lead to the death of dopaminergic neurons.

 

Global genetics consortium to screen families with Parkinson's disease

The Global Parkinson's Genetics Program (GP2, http://gp2.org/) is a collaborative effort that has recently been established to improve the understanding on the genetic architecture of PD globally. ^[5,6] Their emphasis is on families from underrepresented populations.

GP2 is interested in recruiting large families with PD (>3 affected family members) and families with early-onset disease (i.e. age at onset (AAO) of <50 years). They are also interested in obtaining DNA samples from both parents of an affected individual, as well as of other affected family members.

Acknowledging the rarity of large PD families and the significant efforts to recruit and obtain blood samples from family members for genetic studies, incentives will be provided (https://monogenic.gp2.org/LargeFamilyIncentive.html). Requirements to participate in GP2 include a GP2-approved consenting process, a blood sample from each participant and relevant clinical information (as summarised in Fig. 1). South African (SA) medical professionals with suitable families in collaboration with the researchers at Stellenbosch University will be able to send DNA and relevant patient information to GP2.

 

 

Benefits to study participants include:

• genetically-confirmed PD diagnosis and improved clinical management

• patient-centred treatment based on the specific pathogenic variant^[7,8]

• if a monogenic cause is identified, presymptomatic testing of family members who could benefit from disease-modifying treatment, when available

• once a causal variant is identified, the proband can possibly enlist in clinical trials targeted at their specific disease-causing gene e.g. inase inhibitors of LRRK2, should they become available^[9]

• ultimately, these genetic findings may aid in the development of novel and more effective drug treatments for PD.

Notably, individuals of African ancestry are distinguished by the greatest levels of genetic diversity worldwide, owing to them being some of the oldest populations, and adaptation of their genomes to changing climates, varying diets and exposure to transmissible diseases over thousands of years.^[10] This genetic diversity may lead to novel genetic discoveries for PD.

In summary, this collaboration with the GP2 consortium aims to raise awareness that PD has a genetic component. Through GP2, SA families with PD can be genetically screened at no cost to the study participants or researchers, and the knowledge gained may be of great benefit to people with PD throughout the world.

Ethics. The research referred to in this editorial was approved by the Human Research Ethics Committee at Stellenbosch University (ref. no. 2002C/059).

Acknowledgements. We thank all study participants for their involvement in the study.

Author contributions. SB and SM conceptualised the article. AB wrote the first draft and compiled the figure. All authors provided critical review, editing, and approved the final version of the manuscript.

Funding. This work is funded by the National Research Foundation of South Africa (Grant 129249).

Conflicts of interest. None.

Abigail Braun

Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa abraun@sun.ac.za

Riaan van Coller

Department of Neurology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa; and Pretoria Institute of Neurology, Die Wilgers, Pretoria, South Africa

Ferzana Hassan Amod

Department of Neurology, Inkosi Albert Luthuli Central Hospital, Cato Manor, Durban, South Africa; and Department of Neurology, Faculty of Medicine and Health Sciences, University of KwaZulu-Natal, Durban, South Africa

Jonathan Carr

Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

Shahida Moosa

Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; and Medical Genetics, Tygerberg Hospital, Cape Town, South Africa

Soraya Bardien

Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; and South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South Africa

 

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