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. Regarding the small subset of highly penetrant monogenic disorders, a positive family history and early disease onset are mostly sufficient to determine the appropriateness of genetic testing in the index case and to inform pre-symptomatic diagnosis in at-risk family members. In more prevalent polygenic non-communicable diseases (NCDs), the use of appropriate eligibility criteria is required to ensure a balance between benefit and risk. An additional screening step may therefore be necessary to identify individuals most likely to benefit from genetic testing. This need provided the stimulus for the development of a pathology-supported genetic testing (PSGT) service as a new model for the translational implementation of genomic medicine in clinical practice. PSGT is linked to the establishment of a research database proven to be an invaluable resource for the validation of novel and previously described gene-disease associations replicated in the South African population for a broad range of NCDs associated with increased cardio-metabolic risk. The clinical importance of inquiry concerning family history in determining eligibility for personalized genotyping was supported beyond its current limited role in diagnosing or screening for monogenic subtypes of NCDs. With the recent introduction of advanced microarray-based breast cancer subtyping, genetic testing has extended beyond the genome of the host to also include tumor gene expression profiling for chemotherapy selection. The decreasing cost of next generation sequencing over recent years, together with improvement of both laboratory and computational protocols, enables the mapping of rare genetic disorders and discovery of shared genetic risk factors as novel therapeutic targets across diagnostic boundaries. This article reviews the challenges, successes, increasing inter-disciplinary integration and evolving strategies for extending PSGT towards exome and whole genome sequencing (WGS) within a dynamic framework. Specific points of overlap are highlighted between the application of PSGT and exome or WGS, as the next logical step in genetically uncharacterized patients for whom a particular disease pattern and/or therapeutic failure are not adequately accounted for during the PSGT pre-screen. Discrepancies between different next generation sequencing platforms and low concordance among variant-calling pipelines caution against offering exome or WGS as a ...

Background. Genetic testing for BRCA mutations has been available in the Western Cape of South Africa since 2005, but practical implementation of genetic counselling and testing has been challenging. Objective. To describe an approach to breast cancer genetic counselling and testing developed in a resource-constrained environment at Tygerberg Hospital in Cape Town, Western Cape. Methods. Genetic counselling is offered in a stepwise manner to our diverse patient population, with a focus on affected probands, and subsequent cascade testing. A record review of BRCA testing between 2005 and 2011 was performed. Results. During this period 302 probands received genetic testing, with increasing numbers tested over time. Of 1 520 women treated for breast cancer since 2008, 226 (14.9%) accepted BRCA testing, and 39 tested positive (17.3% of those tested, and 2.6% of all women). Common founder mutations were detected in 11.9% of women (36/302), and comprised 73% (36/49) of mutations detected. Cascade testing increased after 2010: 16 female and 4 male family members of 19 probands accepted testing, with 6 positives being detected. Conclusion. A protocol-driven approach focusing on probands, with initial pre-test counselling by primary care staff has proven effective in establishing the service. Involvement of a clinical geneticist/genetic counsellor has permitted more detailed post-test counselling and increased use of cascade testing.

The COVID-19 pandemic forced changes to online teaching worldwide. The Clinical Anatomy journal club (JC) is key in the Bachelor of Science Honours (BScHons) programme and aims to improve scientific appraisal and communication abilities in anatomical research. An online JC through synchronous contact between members was deemed fitting as it could bridge the newly enforced geographical limitations due to the national lockdown in South Africa. Although common in clinical specialties, there are no published reports of anatomy themed online JCs. This project aimed to develop, implement, and appraise a synchronous virtual JC for Clinical Anatomy during the COVID-19 South African lockdown. A qualitative exploratory study design within an interpretive/constructivist paradigm was followed and aimed to explore students’ perceptions of a virtual anatomy JC during the lockdown. The study was conducted at a South African institution, within the BScHons programme, and all enrolled students were invited to participate. Upon receipt of informed consent, an anonymous questionnaire was administered via Moodle for the BScHons students. The responses were analysed by thematic analysis, codes were developed, and themes were generated. Two main themes were generated from the results: the first related to the virtual format of the JC and the second focused on the content and topics covered during the JC sessions. The Clinical Anatomy staff and students adapted rapidly to the virtual JC and formed a community of practice. The benefits of teaching and learning within JC were maintained during the virtual format. It is envisioned that the JC will continue in a hybrid format (face-to-face and virtual) in future academic years. Supplementary Information The online version contains supplementary material available at 10.1007/s40670-021-01325-8.

Background. Mammographic screening is carried out at public sector hospitals as part of clinical practice. Objective. We report the experience of such screening at Tygerberg Academic Hospital (TBAH), a tertiary referral hospital in the Western Cape Province, South Africa. Methods. All mammograms performed between 2003 and 2012 at TBAH were analysed regarding patient demographics, clinical data, indication and outcome according to the American College of Radiology Breast Imaging Reporting and Data System (BIRADS). Screening mammography was offered to patients >40 years of age and mammograms were read by experienced breast surgeons. Patients with BIRADS 3 and 4 lesions were recalled for short-term follow-up, further imaging or tissue acquisition. Patients with BIRADS 5 lesions were recalled for tissue acquisition. Further imaging, method of tissue acquisition, histology results and use of neo-adjuvant therapy were also recorded. Results. Of 16 105 mammograms, 3 774 (23.4%) were carried out for screening purposes. The median age of patients undergoing screening was 54 years. Of 407 women with mammograms that were reported as BIRADS 3 -5 (10.8% of screening mammograms), 187 (46% of recalled women) went on to have further imaging only. Tissue was acquired in 175 patients (43% of recalled women), comprising a biopsy rate of 4.6% of the total series. The malignancy rate in cases in which tissue acquisition was done was 25%. Forty-three breast cancers were diagnosed (11.4/1 000 examinations). Of the cancers, nine (31%) were ductal carcinomas in situ. Of 20 invasive cancers, nine (45%) were <10 mm in size. Of the invasive cancers, 40% were node-positive. Conclusions. The cancer diagnosis rate indicates a high breast cancer load in an urbanised population.