Clinical utility of next-generation sequencing for the molecular diagnosis of monogenic diabetes

Abstract

Monogenic diabetes resulting from mutations that primarily reduce insulin-secreting pancreatic β-cell function accounts for 1–2% of all cases of diabetes, and is genetically and clinically heterogeneous. Currently, genetic testing for monogenic diabetes relies on selection of the appropriate gene for analysis based on the availability of comprehensive phenotypic information, which can be time consuming, costly and can limit the differential diagnosis to a few selected genes. In recent years, the exponential growth in the field of high-throughput capture and sequencing technology has made it possible and cost effective to sequence many genes simultaneously, making it an efficient diagnostic tool for clinically and genetically heterogeneous disorders such as monogenic diabetes. Making a diagnosis of monogenic diabetes is important as it enables more appropriate treatment, better prediction of disease prognosis and progression, and counseling and screening of family members. We provide a concise overview of the genetic etiology of some forms of monogenic diabetes, as well as a discussion of the clinical utility of genetic testing by comprehensive multigene panel using next-generation sequencing methodologies.