Maturity onset diabetes of the young and beyond: the changing face of single-gene diabetes
Thomas W. Laver, Kashyap Patel
Abstract
Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes. A genetic diagnosis can help tailor treatment. However, it is vital to test the right genes. This review discusses the need to test the correct genes and widen the genes that are included on panels while also discussing examples of genes that should be removed from panels due to insufficient evidence. This is important to ensure the maximum number of patients receive a genetic diagnosis while avoiding misdiagnosis and mistreatment. To maximize the cost-benefit of genetic testing, we need to select the right patients for genetic testing-this review discusses criteria that increase the chance of a patient having a monogenic cause of their diabetes. Reduced penetrance, where some individuals have the pathogenic genotype but do not exhibit the phenotype, is now known to be increasingly common in MODY and other monogenic disorders. This has important implications when a variant is identified in an unaffected individual. This review highlights recent work that polygenic risk may play a role in determining penetrance.