Clinical genetic testing in endocrinology: Current concepts and contemporary challenges

摘要

Abstract Recent advances in DNA sequencing technology have led to an unprecedented period of disease‐gene discovery offering many new opportunities for genetic testing in the clinical setting. Endocrinology has seen a rapid expansion in the taxonomy of monogenic disorders, which can be detected by an expanding portfolio of genetic tests in both diagnostic and predictive settings. Successful testing relies on many factors including the ability to identify those at increased risk of genetic disease in the busy clinic as well as a working knowledge of the various testing platforms and their limitations. The clinical utility of a given test is dependent upon many factors, which include the reliability of the genetic testing platform, the accuracy of the test result interpretation and knowledge of disease penetrance and expression. The increasing adoption of “high‐content” genetic testing based on next‐generation sequencing (NGS) to diagnose hereditary endocrine disorders brings a number of challenges including the potential for uncertain test results and/or genetic findings unrelated to the indication for testing. Therefore, it is increasingly important that the clinician is aware of the current evolution in genetic testing, and understands the different settings in which it may be employed. This review provides an overview of the genetic testing workflow, focusing on each of the major components required for successful testing in adult and paediatric endocrine settings. In addition, the challenges of variant interpretation are highlighted, as are issues related to informed consent, prenatal diagnosis and predictive testing. Finally, the future directions of genetic testing relevant to endocrinology are discussed.