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Genetic, metabolic and clinical characteristics of maturity onset diabetes of the young Velho G; Froguel PEur J Endocrinol 1998[Mar]; 138 (3): 233-9Maturity onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date, three MODY genes have been identified on chromosomes 20q (MODY1/hepatic nuclear factor (HNF)-4alpha), 7p (MODY2/glucokinase) and 12q (MODY3/HNF-1alpha). Mutations in MODY2/glucokinase result in mild chronic hyperglycaemia as a result of reduced pancreatic beta-cell responsiveness to glucose, and decreased net accumulation of hepatic glycogen and increased hepatic gluconeogenesis after meals. In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects, and by major hyperglycaemia associated with microvascular complications. The role of the three known MODY genes in susceptibility to the more common late-onset NIDDM remain uncertain. Genetic studies seem to exclude a role as major susceptibility genes, but leave unresolved whether they may have a minor role in a polygenic context or an important role in particular populations.|*DNA-Binding Proteins[MESH]|*Diabetes Mellitus, Type 2/classification/complications/genetics/metabolism[MESH]|*Homeodomain Proteins[MESH]|*Nuclear Proteins[MESH]|Adolescent[MESH]|Adult[MESH]|Basic Helix-Loop-Helix Leucine Zipper Transcription Factors[MESH]|Child[MESH]|Female[MESH]|Glucokinase/*genetics/metabolism[MESH]|Glycogen/metabolism[MESH]|Hepatocyte Nuclear Factor 1[MESH]|Hepatocyte Nuclear Factor 1-alpha[MESH]|Hepatocyte Nuclear Factor 1-beta[MESH]|Hepatocyte Nuclear Factor 4[MESH]|Humans[MESH]|Liver/enzymology/metabolism[MESH]|Male[MESH]|Phosphoproteins/*genetics[MESH]|Prevalence[MESH]|Trans-Activators/*genetics[MESH]|Transcription Factors/*genetics[MESH] |
