A GENE FOR MATURITY-ONSET DIABETES OF THE YOUNG (MODY) MAPS TO CHROMOSOME 12Q

Maturity-onset diabetes of the young (MODY) is a subtype of non-insuli n dependent diabetes mellitus, with early age of onset. MODY is geneti cally heterogeneous, associated with glucokinase mutations and a locus on chromosome 20q; in about 50% of cases, its genetic background is u nknown. We have studied 12 families in which MODY is unlinked to eithe r glucokinase or chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on chromosome 12q, most likel y within a 7 centimorgan interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this chromosome region in appro ximately 50% of families in a heterogeneity analysis. These MODY patie nts exhibit major hyperglycaemia with a severe insulin secretory defec t, suggesting that the causal gene is implicated in pancreatic beta-ce ll function.