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

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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

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.

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Authors and Affiliations

  1. Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Mahin Hashemipour, Neda Mostofizadeh, Mohammadmehdi Ghasemi, Noushin Rostampour, Elham Hashemi Dehkordi & Silva Hovsepian

  2. Medical Genetics Laboratory of Genome, Isfahan, Iran

    Mahdiyeh Behnam

  3. Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran

    Mahdiyeh Behnam

  4. Imam Hossien Children’s Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

    Silva Hovsepian

Authors
  1. Mahin Hashemipour
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  2. Neda Mostofizadeh
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  3. Mohammadmehdi Ghasemi
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  4. Mahdiyeh Behnam
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  5. Noushin Rostampour
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  6. Elham Hashemi Dehkordi
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  7. Silva Hovsepian
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Contributions

All authors contributed to the concept and design of the study and participated actively in all stages of the work including data collection, analysis, and preparing the first draft of the paper, and all of them have read and confirmed the manuscript.

Corresponding authors

Correspondence to Neda Mostofizadeh or Silva Hovsepian.

Ethics declarations

Data of patients between the years 2006 and 2017 that had been previously registered were collected. The current study was confirmed by the research committee and regional ethics committee of Isfahan University of Medical Sciences with research and ethics codes of 397529 and IR.MUI.MED.REC.1398.168, respectively. The protocol and methods of the current study were described in details for parents, and written informed consent was obtained from the parents of each patient.

Conflict of interest

The authors declare no competing interests.

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Hashemipour, M., Mostofizadeh, N., Ghasemi, M. et al. Molecular genetic analysis of the insulin gene variants in Iranian patients with permanent neonatal diabetes. Int J Diabetes Dev Ctries 43, 821–828 (2023). https://doi.org/10.1007/s13410-022-01152-6

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  • DOI: https://doi.org/10.1007/s13410-022-01152-6

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