Most valuable breakthroughs in the genetics of type 2 diabetes mellitus have arisen from familial linkage analysis of maturity-onset diabetes of the young, an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin-secretion defects. Despite its low prevalence, MODY is not a single entity but presents genetic, metabolic, and clinical heterogeneity. MODY can result from mutations in at least six different genes;one encodes the glycolytic enzyme glucokinase, which is an important glucose sensor, whereas all the others encode transcription factors that participate in a regulatory network essential for adult beta cell function. Additional genes, yet unidentified, may explain the other MODY cases unlinked to a mutation in the known genes.
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