Application of advanced molecular technology in the diagnosis and management of genetic disorders in South Africa

Abstract

Background. Genetic testing has evolved from a niche speciality for diagnosis of rare disorders and carrier screening to subtyping of complex medical conditions for targeted treatment. Genes causing monogenic disorders are well characterised, but risk management of multifactorial and polygenic disorders guided from the genetic background remains a challenge. 

Objective. This study describes the use of a pathology-supported genetic testing (PSGT) strategy designed to facilitate the move from single- to multi-gene testing and next-generation sequencing (NGS).  

Methods. In contrast to direct-to-consumer genetic testing, PSGT requires preselection of patients and data integration to determine current and future risk implications. To enable this process, a genomics database resource generated at the interface between the laboratory and clinic is available for clinical interpretation.  

Results. The PSGT approach led to the development of testing algorithms for improved clinical management of patients with cancer and other complex disorders with a genetic component. Local evidence is presented to demonstrate the application of PSGT for assessment of clinical relevance in patients with rare germline variants and functional polymorphisms underlying shared disease pathways.

Conclusion. PSGT is ideally suited to serve as a screening step for microarray analysis and whole genome/exome sequencing as the next frontier in personalised medicine. Use of these advanced molecular technologies to match genotype with phenotype provides a resource for diagnosis and discovery over a lifetime.