ABSTRACT
Breast cancer is highly prevalent in South Africa, and up to 10% of breast cancer cases may be hereditary. The landscape of genetic testing options for hereditary breast cancer (HBC) has changed significantly over the past decade, and healthcare providers are faced with multiple options when referring breast cancer patients for genetic testing. We have performed a retrospective study of 3 years' worth of breast cancer genetic testing referrals to our laboratory. While Afrikaner and Ashkenazi Jewish founder screens may be appropriate as first-line tests in a limited subset of patients, we have shown that in the majority of cases it is more effective to adopt a multigene panel approach. While variants in the BRCA1 and BRCA2 genes still account for a significant proportion of cases, close to 40% of pathogenic variants were found in genes other than BRCA1 or BRCA2. There are many factors that healthcare providers should consider when requesting genetic testing for breast cancer patients and families, including family history, ancestral background, cost, medical aid scheme reimbursement and scope of testing. We summarise our findings and provide advantages and disadvantages of each approach, with the aim of assisting clinicians and genetic counsellors to make appropriate testing decisions.
Subject(s)
Breast Neoplasms/diagnosis , Genetic Testing , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Founder Effect , Humans , Multifactorial Inheritance , Retrospective Studies , South Africa , Ubiquitin-Protein Ligases/geneticsABSTRACT
Retinal degenerative disorders (RDDs) encompass a group of inherited diseases characterised by vision loss. The genetic and clinical complexity poses a challenge in unravelling the molecular genetic aetiology of this group of disorders. Furthermore, the population diversity in South Africa (SA) presents researchers with a particularly complicated task. Rapid advances in the development of cutting-edge technological platforms over the past two decades, however, have assisted in overcoming some of the challenges. The RDD research team has utilised these escalating technologies, which has facilitated a corresponding increase in molecular diagnoses. A biorepository has been established and comprises ~3 200 patient DNA samples archived with many forms of RDD (including retinitis pigmentosa, macular dystrophies, Stargardt disease, Leber congenital amaurosis, Usher syndrome and Bardet Biedl syndrome). A comprehensive review is presented of the SA journey spanning 25 years, into elucidating the molecular genetic basis of various forms of RDD in SA.
