Incorporating familial risk, lifestyle factors, and pharmacogenomic insights into personalized noncommunicable disease (NCD) reports for healthcare funder beneficiaries participating in the Open Genome Project.

Introduction: An ethics-guided decision-making framework was developed for applying pathology-supported genetic testing, a multifaceted pharmacodiagnostic approach that translates population risk stratification into clinical utility. We introduce this service, supported by the Open Genome Project, which aligns with the beneficence principle in personalized medicine.

Methods: Genetic testing of six noncommunicable disease pathways was conducted as part of a pilot program, benchmarked against a readiness checklist for implementation of genomic medicine in Africa.

Whole Exome Sequencing in South Africa: Stakeholder Views on Return of Individual Research Results and Incidental Findings.

The use of whole exome sequencing (WES) in medical research is increasing in South Africa (SA), raising important questions about whether and which individual genetic research results, particularly incidental findings, should be returned to patients. Whilst some commentaries and opinions related to the topic have been published in SA, there is no qualitative data on the views of professional stakeholders on this topic. Seventeen participants including clinicians, genomics researchers, and genetic counsellors (GCs) were recruited from the Western Cape in SA.

Globally Rare Variants With Founder Haplotypes in the South African Population: Implications for Point-of-Care Testing Based on a Single-Institution Next-Generation Sequencing Study.

Breast cancer patients historically benefitted from population-based genetic research performed in South Africa, which led to the development of founder-based diagnostic tests. With the advent of next-generation sequencing (NGS) technologies, the clinical utility of limited, targeted genetic assays were questioned. The study focused on mining NGS data obtained from an extensive single-institution NGS series (n=763).

Optimizing G6PD testing for case management and beyond: why sex, counseling, and community engagement matter.

Safe access to the most effective treatment options for   malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against  hypnozoites. Until recently, only qualitative tests were available in most settings.

Pioneering Informed Consent for Return of Research Results to Breast Cancer Patients Facing Barriers to Implementation of Genomic Medicine: The Kenyan BRCA1/2 Testing Experience Using Whole Exome Sequencing.

Introduction: Obtaining informed consent from study participants and disseminating the findings responsibly is a key principle required for ethically conducted clinical and genetic research. Reports from African researchers providing feedback on insights gained during the return of whole exome sequencing (WES) results to breast cancer patients treated in resource-limited settings is lacking.

Aim: The empirical process used to fill this gap in relation to variant detection using WES provided unique insights incorporated into a pathology-supported genetic testing algorithm for return of research results to Kenyan breast cancer patients.

Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway.

Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two mutation-negative breast cancer patients from the same family for WES.

Genomic medicine and risk prediction across the disease spectrum.

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures.

Significance of dietary folate intake, homocysteine levels and MTHFR 677 C>T genotyping in South African patients diagnosed with depression: test development for clinical application.

Low folate intake in the presence of the functional MTHFR 677 C > T (rs1801133) polymorphism is an important cause of elevated homocysteine levels previously implicated in major depressive disorder (MDD) and many other chronic diseases. In this study the clinical relevance and inter-relationship of these aspects were evaluated in 86 South African patients diagnosed with MDD and 97 population-matched controls participating in a chronic diseases screening program. A questionnaire-based clinical and nutrition assessment was performed, homocysteine levels determined, and all study participants genotyped for MTHFR 677 C > T (rs1801133) using allele-specific TaqMan technology.

CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application.

Approximately 25% of clinically important drugs and numerous environmental carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. In this study we determined the appropriateness of adding CYP2D6 genotyping to the breast cancer genetic testing options already available in South Africa, which include BRCA mutation screening and transcriptional profiling to assess estrogen receptor (ER) status.