Enhancing Diagnostic Yield of Monogenic Diabetes Through Phenotypic and Molecular Reanalysis of 128 Individuals With Young Onset Hyperglycemia: Highlighting the Significance of Accurate Case Characterization

The study aimed to improve the molecular diagnostic accuracy for monogenic diabetes in 128 unresolved cases by reanalyzing both phenotypic and genotypic data. Initially, these cases were investigated using a next-generation sequencing panel targeting 51 nuclear genes and the mitochondrial genome. Through comprehensive reanalysis, the diagnostic yield increased from 9% to 26%. Phenotypic reevaluation excluded 62 atypical cases, while genotypic reanalysis identified 5 previously missed molecular defects. The study concludes that combining genotypic and phenotypic reanalysis significantly enhances diagnostic precision for monogenic diabetes.