Genetic Variants of the HNF1 Gene in Maturity Onset Diabetes of the Young (MODY3) in Egyptian Children

Abstract

Maturity Onset Diabetes of the Young (MODY), which comprises between 1 to 5% of all the cases of diabetes, is characterized by monogenic autosomal dominant inheritance, early onset (usually before 25 years of age), with dysfunction of pancreatic  cells. This study aimed to explore possible mutations in the HNF-1α gene with relation to Egyptian patients clinically diagnosed as MODY-3 diabetes. Also to relate the clinical profile of these patients with their molecular characterization. Genomic DNA was extracted from blood of 8 diabetic children patients characterized by C-peptide ≥ (1.3 nmol/L) with body mass index (MBI) ranging from obese to severe obese. Other clinical diagnosis were FBS (180 mg/dl ±54.32), PPS (265.6 mg/dl ± 74.7), HbA1c (≥ 8.93% ± 3.9) and HOMA-IR (0.96 ± 0.366). Extracted DNA subjected for PCR amplification reaction with oligonucleotides flanking regions of promoter and 10 exons of HNF-1α gene. Exact sized of amplified fragments were confirmed by electrophoresis, and then samples were purified and sequenced to recognize the mutations. Molecular analysis of the amplified fragments revealed twenty-seven variations in the HNF-1α gene. Five of them were detected in the promoter region and other twenty-two mutations