A MOLECULAR STUDY OF HNF-1alpha GENE MUTATIONS IN MODY3 EGYPTIAN PATIENTS

Abstract

Mutations in hepatocyte nuclear factor-1alpha (HNF-1alpha)gene causeone type of maturity onset diabetes of the young (MODY) calledMODY3, which is characterized by poor insulin secretion in response to glucose.Our study is focused on HNF-1alpha gene related to MODY3. The aim of the present study is to detect the mutations in theHNF-1alphagenein the Egyptian patients for the first time,and to compare the results for Egyptian patients with those in other regions of the world. The present work includes eight Egyptian patients diagnosed with MODY3, their ages were between 12 and 17 years old.The directsequence analyses of the exons 6, 7, 8, 9 and 10 and promoter 1 of HNF-1alphagenewere performed. The obtained results of the sequences were aligned with the normal ones which were obtained from "NCBI" reference sequence database with the accession number NM_000545.5. Theobtained results yield single nucleotide polymorphism (SNP), of which are the missense and silent mutations. It was observed that the maximum number of the variants was theSNPvariants that werefound in the promoter 1, intron 7 and intron 9.Twenty different SNPs were detected in the promoter 1 only in about 75% of all patients (6 from 8 patients). The SNP variant c.1501+7G>A wasdetected in intron 7 and represented about 62.5% of all patients (5 from 8 patients), while the SNP variant c.1769-24T>C was found in intron 9 in about 75% of all patients (6 from 8 patients). The twoprevious SNP variantsdetected in intron regions were recorded before in different locations all over the world.