Abstract
Monogenic forms of diabetes represent an uncommon but very heterogeneous subset of the disease, with variable associated clinical features and key differences in treatment options. In this review, we discuss how advances in precision medicine and genomic sequencing have enhanced our understanding of the aetiology and clinical variability of monogenic diabetes. We highlight current global challenges, including the over-representation of individuals of European genetic ancestry in research studies, which complicates diagnosis in non-European populations, and national disparities in genetic testing strategies, which influence diagnostic accuracy. Additionally, we address issues in variant interpretation stemming from the increased understanding of variable penetrance in monogenic diabetes and the need to expand current reference datasets to exclude common genetic variation. Finally, we explore future directions, including the potential benefits of ongoing genetic studies for under-represented populations, the benefits and potential pitfalls of newborn screening programmes, and the potential of stem cell-derived islet transplantation and glucagon-like peptide- 1 receptor agonists as treatments for some forms of monogenic diabetes.