Identification of insulin gene variants in neonatal diabetes

J Matern Fetal Neonatal Med. 2017 May;30(9):1035-1040. doi: 10.1080/14767058.2016.1199674. Epub 2016 Jul 4.

Abstract

Objectives: Permanent neonatal diabetes (PNDM) is caused by mutations in the genes responsible for the synthesis of different proteins that are important for the normal behavior of beta cells in the pancreas. Mutations in the insulin gene (INS) are considered as one of the causes of diabetes in neonates. This study aimed to investigate the genetic variations in the INS gene in a group of Egyptian infants diagnosed with PNDM.

Methods: We screened exons 2 and 3 with intronic boundaries of the INS gene by direct gene sequencing in 30 PNDM patients and 20 healthy controls. A detailed clinical phenotyping of the patients was carried out to specify the diabetes features in those found to carry an INS variant.

Results: We identified five variants (four SNPs and one synonymous variant), c(0).187 + 11T > C, c.-17-6T > A, c.*22A > C, c.*9C > T, and c.36G > A (p.A12A), with allelic frequencies of 96.7%, 80%, 75%, 5%, and 1.7%, respectively. All showed no statistically significance difference compared with the controls, with the exception of c.*22A > C.

Conclusion: Genetic screening for the INS gene did not reveal an evident role in the diagnosis of PNDM.

Keywords: DNA sequencing; insulin (INS) gene; mutations; permanent neonatal diabetes (PND).

MeSH terms

  • Case-Control Studies
  • DNA Mutational Analysis
  • Diabetes Mellitus / genetics*
  • Exons / genetics
  • Female
  • Genetic Variation*
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / genetics
  • Insulin / genetics*
  • Male
  • Mutation

Substances

  • Insulin

Supplementary concepts

  • Diabetes Mellitus, Permanent Neonatal