Molecular genetic analysis of the insulin gene variants in Iranian patients with permanent neonatal diabetes

Background We aimed to determine the frequency of mutations in 3 common genes causing neonatal diabetes mellitus (NDM) in Isfahan. Methods This study was performed on 15 patients with permanent NDM (PNDM). KCNJ11, INS, and ABCC8 gene mutations were examined in all patients. Other related gene mutations were also examined if the first three mentioned mutations were negative. The patients were classified into two groups based on the time of NDM diagnosis (before 6 and 6-12 months of age). Results Patients with PNDM who were diagnosed before 6 months of age had more concomitant anomalies than those diagnosed between 6 and 19 months of age (p < 0.05). The genetic study did not show any mutation in ABCC8, KCNJ11, and INS genes. Evaluation of other gene mutations indicated that 3 patients (two boys and one girl) had a homozygous mutation in EIF2AK3, one patient (boy) had a homozygous mutation in PTF1A, and also one patient (boy) had a homozygous mutation in GLIS3 gene which are all considered as rare genes which could cause NDM. All of the patients with mutations were diagnosed before 6 months of age. Four out of the five patients were male and had parental consanguinity (2nd and 3rd degree). Conclusion We found that mutations in KCNJ11, INS, and ABCC8 are not the common cause of PNDM in our population, and mutations in EIF2AK3, PTF1A, and GLIS3 genes are more frequent. The PNDM cases and their related reported mutation were related to the syndromic form of NDM, and all of them were diagnosed before 6 months of age.