ANALYSIS OF THE GLUCOKINASE GENE IN MEXICAN FAMILIES DISPLAYING EARLY-ONSET NON-INSULIN-DEPENDENT DIABETES-MELLITUS INCLUDING MODY FAMILIES

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common for m of diabetes, affecting 5% of the general population, Genetic factors play an important role in the development of the disease, While in ot her populations NIDDM is usually diagnosed after the fifth decade of l ife, in Mexico a large proportion of patients develop the disease at a n early age (between the third and the fourth decade), In Caucasian po pulation, mutations in the glucokinase gene, the TCF1, and TCF14 genes , have been identified in a subgroup of early-onset NIDDM patients den ominated MODY (maturity-onset diabetes of the young), which show an au tosomal dominant pattern of inheritance, As a first step in the molecu lar characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysi s and/or direct sequencing in 26 individuals from 22 independent famil ies, where at least four can be classified as MODY. No mutations were detected in the exons or the intron-exon boundaries of the gene in any of the screened individuals, The phenotype and clinical profile of so me of the studied patients is compatible with that of patients carryin g mutations in the TCF1 or TCF14 genes, while others may carry mutatio ns in different loci, Through computer simulation analysis we identifi ed at least four informative families which will be used for further l inkage studies. (C) 1997 Wiley-Liss, Inc.