Staff Involved

  • Prof. Ambrose Wonkam
  • Ms. Lebogang Montewa
  • Prof. Jantina de Vries
  • Ms. Dimpho Ralefala
  • Dr. Karen Kengne
  • Prof. Mogomotsi Matshaba
  • Dr. Mary Kasule
  • Prof. Séraphin Nguefack
  • Dr. Emile Chimusa
  • Professor Dan J. Stein
  • Dr Vicki Marsh
  • Dr Tindana
  • Dr Marsha Treadwell
  • Benjamin Berkman
  • Dr Christian D. Bope
  • Ms. Olivia Mashabane

IFGeneRA

A key ethical challenge in genomics research relates to whether and which individual genetic research results ought to be fed back to research participants. Whilst recent years have seen a flurry of publications describing normative, empirical and practical considerations on this topic, it has received virtually no attention from African scholars. Yet, with the rise of African genomics research, the question of which findings should be fed back, when and how, is taking on prominence. The Individual Findings in Genetics Research in Africa (IFGeneRA) ELSI Collaborative Centre works to develop a progressive evidence base that will inform the development of context- and country specific policies for the return of individual genetic research results in genomics research in Africa. 

About

Background

In the context of Genetic/Genomics research in Africa in general, and H3Africa consortium specifically,  one challenge complicating discussions relating to the feedback of individual genetic research results, including incidental findings (IFs), relates to the relative absence of a clear understanding of a) the scope of the problem, i.e. the actual likelihood by which actionable pathogenic variants may be uncovered in African populations and b) the financial impact that a policy to reveal such variants may have on researchers, individuals and the healthcare system. A third complicating factor is that normative discussions about the feedback of individual genetic results, including IFs, have not substantively considered the impact of practical obligations, in a context on resources constraints or poor exposure to genetic medicine practice or formal genetic knowledge.

 Project Aim

Overall, IFGeneRA aims to generate and synthesize evidence and insights from our various projects into the development of a policy proposal for the return of individual genetic research findings for African genomics research. Using the combined expertise and networks of all Centre investigators, we will liaise with regulators in Botswana, Cameroon and South Africa to facilitate the adaptation of such a policy in national regulation.

The IFGeneRA H3Africa ELSI Collaborative Centre will a) collect empirical evidence from a wide range of stakeholders in both rural and urban settings in three African countries, b) combine methodologies from genetic counselling, social science, anthropology, bioinformatics, health economics and normative ethical analysis to progressively develop this evidence base, and c) test the wider acceptability and applicability of findings we generate in a continental survey that will be administered to relevant stakeholders throughout Africa.

Fragile X syndrome

Fragile X Syndrome- Return of genetic findings

The aim was to retrospectively investigate the effect of a genetic diagnosis of a monogenic condition, on families and community members from a village in rural Cameroon, by:

  1. a) Exploring the impact of the Fragile X syndrome (FXS) diagnosis on participants who received genetic results, and to use retrospective cascade counselling to engage other family members affected by the same condition.
  2. b) Exploring community views on FXS, the curse explaining patterns of inheritance, traditional knowledge of genetics and gendered blame.

 What is Fragile X syndrome?

Fragile X syndrome is the most common inherited cause of intellectual disability worldwide. Fragile X syndrome can affect both males and females, however, females have milder symptoms than males. Apart from the moderate intellectual disability in boys and mild intellectual delay in girls, individuals with Fragile X syndrome may also have global developmental delay, autism-like behaviour, attention deficit hyperactivity disorder (ADHD) and language and communication challenges.

Genetics of Fragile X Syndrome

Fragile X syndrome is a monogenic condition caused by a DNA change in the FMR1 gene. Read more

Research approach

Information session

Researchers reached out to a community in Cameroon affected by Fragile X Syndrome. We started with culturally-sensitive discussions  on Fragile X syndrome.

Informed consent

After the  information session those interested in participating were given the opportunity to provide informed consent to participate in the study.

Sample collection & genetic testing

Blood samples were collected from participants and sent for diagnostic genetic testing.

Feedback of findings

Individual genetic findings were provided by staff trained in genetic counselling. At the result session, the results were discussed and contact details were given to each person if they required further information or support

Exploring participant experiences

More research was then done to explore the participants’ knowledge of Fragile X syndrome and the way it impacted their family and community life. This exploration was done via interviews held with the family members. 

Documentary creation

After the research was complete, a short documentary was created to summarize the participants insights and experiences of Fragile X syndrome. The documentary encompasses the testing process, interviews, and reflections on the condition within the community

Feedback of findings

The documentary was shown to the research participants and thereafter their feedback was acquired

View the Documentary

Engaging stakeholders
IFGeneRA_engaging

We aimed to better understand the expectations and preferences for feedback of individual genetic research findings of a) genomic research participants and b) people involved in developing, implementing and applying ethical standards and policies for return of individual study results in genomics research in Botswana and South Africa. 

Research approach 

Firstly, we aimed to explore expectations and preferences for feedback of individual genetic research findings with (parents of) participants involved in genomics research in Botswana and South Africa. We conducted deliberative Focus Group Discussions with research participants in genomics research. In Botswana, we worked with parents of children and adolescents involved in the H3Africa CafGen project. In South Africa, we worked with parents of children and adolescents involved in genomics research on neurodevelopmental conditions. 

Secondly, we explored the views on feedback of individual pertinent and incidental genetic research results with people involved in developing, implementing and applying ethical standards and policies for return of individual study results in genomics research in Botswana and South Africa through in-depth interviews. 

Engagement tools 

This project adapted of two Drama of DNA scripts dealing with issues of return of results to be more suitable for African settings. We engaged with the scientific community, school governing boards and parents or caregivers of children with learning difficulties in South Africa. Furthermore, this project has provided a rich understanding of the challenges and opportunities of feeding back genetic results in Botswana which can be translated to other African settings.

Practical and Normative Considerations

In Project 3, we will focus on exploring practical and normative considerations relating to decisions to feedback findings in African genomics research. We will a) host a meeting with medical genetics and genomics experts to consider which kinds of incidental findings should be considered for feedback in light of what is known about African population genetic variation; b) identify the frequency of these reportable variants in existing Whole Exome Sequencing datasets about 750 participant from Botswana and Cameroon, 1000 genome Project and from the H3Africa consortium, and c) conduct a health economics study to investigate the hypothetical cost of reporting back those findings to affected participants, including the cost of confirming research results. In Step 2 of Project 3 we will conduct d) a normative ethical analysis of ethics literature describing obligations to (not) feedback individual genetic findings for researchers based in low- and middle income African countries, and e) drawing on the findings from the three projects to develop a survey exploring wider (continental) approaches to practical and ethical considerations relating to the feedback of individual genetic research results, including incidental findings.

Publications
  1. Diedericks A, Bruwer Z, Laing N, Eastman E, De Vries JV, Donald KA, Robinson EB, Newton CR, Abubakar A. Parental Perspectives Regarding the Return of Genomic Research Results in Neurodevelopmental Disorders in South Africa: Anticipated Impact and Preferences. Res Sq [Preprint]. 2024 Jun 11:rs.3.rs-4448155. doi: 10.21203/rs.3.rs-4448155/v1. PMID: 38946993
  2. Ewuoso C, Berkman B, Wonkam A, de Vries J. Should institutions fund the feedback of individual findings in genomic research? J Med Ethics. 2024 Jul 23;50(8):569-574. doi: 10.1136/medethics-2021-107992. PMID: 35710317
  3. Ewuoso C, Wonkam A, de Vries J. Epistemic justice, African values and feedback of findings in African genomics research. Glob Bioeth. 2022 Sep 21;33(1):122-132. doi: 10.1080/11287462.2022.2124019. eCollection 2022. PMID: 36185769
  4. Fontes Marx M, Ataguba JE, de Vries J, Wonkam A. Systematic Review of the Economic Evaluation of Returning Incidental Findings in Genomic Research. Front Public Health. 2021 Jul 1;9:697381. doi: 10.3389/fpubh.2021.697381. eCollection 2021. PMID: 34277554
  5. Kamga KK, De Vries J, Nguefack S, Munung SN and Wonkam A (2020). Lived Experiences of Fragile X Syndrome Caregivers: A Scoping Review of Qualitative Studies. Front. Neurol. 11:128. https://doi:10.3389/fneur.2020.00128
  6. Kasule M, Matshaba M, Mwaka E, Wonkam A, de Vries J. Considerations of Autonomy in Guiding Decisions around the Feedback of Individual Genetic Research Results from Genomics Research: Expectations of and Preferences from Researchers in Botswana. Glob Health Epidemiol Genom. 2022 Mar 31;2022:3245206. doi: 10.1155/2022/3245206. eCollection 2022. PMID: 35441036
  7. Kasule M, Matshaba M, Wonkam A, de Vries J. Feeding back of individual genetic results in Botswana: mapping opportunities and challenges. BMC Med Ethics. 2023 Jun 3;24(1):37. doi: 10.1186/s12910-023-00912-1. PMID:37270597
  8. Kengne Kamga K, De Vries J, Nguefack S, Munung NS, Wonkam A. Explanatory models for the cause of Fragile X Syndrome in rural Cameroon. J Genet Couns. 2021;00:1–10. https://doi.org/10.1002/jgc4.1440
  9. Kengne Kamga K, Munung NS, Nguefack S, Wonkam A, De Vries J. Negotiating political power and stigma around fragile X Syndrome in a rural village in Cameroon: A tale of a royal family and a community. Mol Genet Genomic Med. 2021;9:e1615. https://doi.org/10.1002/mgg3.1615
  10. Kengne Kamga K, Nguefack S, Minka K, Wonkam Tingang E, Esterhuizen A, Nchangwi Munung S, De Vries J, Wonkam A. Cascade Testing for Fragile X Syndrome in a Rural Setting in Cameroon (Sub-Saharan Africa). Genes (Basel). 2020 Jan 28;11(2):136. https://doi:10.3390/genes11020136
  11. Matimba A, Ali S, Littler K, Madden E, Marshall P, McCurdy S, Nembaware V, Rodriguez L, Seeley J, Tindana P, Yakubu A, de Vries J; H3Africa Ethics and Community Engagement Working Group. Guideline for feedback of individual genetic research findings for genomics research in Africa. BMJ Glob Health. 2022 Jan;7(1):e007184. doi: 10.1136/bmjgh-2021-007184. PMID: 35017180
  12. Musvipwa F, Wonkam A, Berkman B, de Vries J. Perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research. BMC Med Ethics. 2024 Jun 7;25(1):67. doi: 10.1186/s12910-024-01068-2. PMID:38849807
  13. Ralefala D, Kasule M, Matshabane OP, Wonkam A, Matshaba M, de Vries J. Participant views on practical considerations for feedback of individual genetic research results: a case study from Botswana. Glob Bioeth. 2023 Apr 12;34(1):1-14. doi: 10.1080/11287462.2023.2192329. eCollection 2023. PMID: 37063478
  14. Ralefala D, Kasule M, Matshabane OP, Wonkam A, Matshaba M, de Vries J. Participants’ Preferences and Reasons for Wanting Feedback of Individual Genetic Research Results From an HIV-TB Genomic Study: A Case Study From Botswana. J Empir Res Hum Res Ethics. 2021 Dec;16(5):525-536. doi: 10.1177/15562646211043985. PMID: 34662218
  15. Van Der Merwe N, Ramesar R, De Vries J. Whole Exome Sequencing in South Africa: Stakeholder Views on Return of Individual Research Results and Incidental Findings. Front Genet. 2022 Jun 8;13:864822. doi: 10.3389/fgene.2022.864822. eCollection 2022. PMID: 35754817
  16. Wonkam A, de Vries J. Returning incidental findings in African genomics research. Nat Genet. 2020 Jan;52(1):17-20. https://doi:10.1038/s41588-019-0542-4
  17. Yéré HM, Machirori M, De Vries J. Unpacking race and ethnicity in African genomics research. Nat Rev Genet. 2022 Aug;23(8):455-456. doi: 10.1038/s41576-022-00506-4. PMID: 35688877
News
Following the establishment of a Medical Genetic Unit in Yaoundé Cameroon, the consultation of a mother of two sons affected with mental retardation allowed a molecular analysis that revealed Fragile X syndrome (FXS).

Community engagement for Genetic Research on Fragile X Syndrome in Cameroon

Following the establishment of a Medical Genetic Unit in Yaoundé Cameroon, the consultation of a mother of two sons affected with mental retardation allowed a molecular analysis that revealed Fragile X syndrome (FXS).

FIND OUT MORE
Fragile X Syndrome (FXS), also known as the most common inherited cause of intellectual disability (ID), is a neurogenic condition that affects twice as many males as females.

Explanatory models for the cause of Fragile X Syndrome in rural Cameroon

Fragile X Syndrome (FXS), also known as the most common inherited cause of intellectual disability (ID), is a neurogenic condition that affects twice as many males as females.

FIND OUT MORE
Fragile X Syndrome (FXS) is the most common monogenic X-linked condition which causes variable degrees of Intellectual Disability (ID), autism spectrum disorder (ASD), delay in acquisition of speech and other cognitive skills; affecting one in 7143 males and one in 11,111 females [1–5]. Some individuals with FXS may present characteristics of facial appearance such as, a large forehead and prominent ears.

Cascade Testing for Fragile X Syndrome in a Rural Setting in Cameroon (Sub-Saharan Africa)

Fragile X Syndrome (FXS) is the most common monogenic X-linked condition which causes variable degrees of Intellectual Disability (ID), autism spectrum disorder (ASD), delay in acquisition of speech and other cognitive skills; affecting one in 7143 males and one in 11,111 females [1–5]. Some individuals with FXS may present characteristics of facial appearance such as, a large forehead and prominent ears.

FIND OUT MORE

Funders & Collaborators