Analysis of the glucokinase gene in Iranian families with maturity onset diabetes of the young

Abstract

Non insulin dependent diabetes mellitus (NIDDM) as a most common form of diabetes is a major public health problem; there is a subgroup of NIDDM patients which develops the disease at an early age and shows a dominant mode of inheritance. This type is nominates Maturity onset diabetes of the young (MODY). The prevalence of MODY is difficult to access as patients with MODY genes mutations are often identified during routine screening for other purposes. MODY2 was linked to mutations in glucokinase gene (GCK), and account for 8-56% of MODY, with the highest prevalence being found in the southern Europe. The aim of this study was to examine the prevalence and nature of mutations in GCK gene in Iranian paients. We have screened GCK mutations by single stranded conformation polymorphism (SSCP) technique of polymerase chain reaction (PCR) in 12 Iranian families with clinical diagnosis of MODY, included 30 patients (eight males and 22 females) and their 21 family members. PCR products with abnormal mobility in denaturing gradient gel electrophoresis (DGGE) were directly sequenced. We identified six novel mutations in GCK gene in Iranian families (corresponding to 36.6% prevalence). Our findings and the last study on MODY1 highlight that in addition to GCK, other MODY genes such as MODY3 and MODYX may play a significant role for diabetes characterized by monogenic autosomal dominant transmission. This is clear that the knowledge of the specific defect can be used to pre-symptomatically identify family members at risk for developing MODY.