Identification of novel variants in neonatal diabetes mellitus genes in Egyptian patients with permanent NDM

  • Hanan MadaniEmail author
  • Rasha Elkaffas
  • Badawy Alkholy
  • Noha Musa
  • Yomna Shaalan
  • Rania Elkaffas
  • Mona Hassan
  • Mona Hafez
  • Sarah E Flanagan
  • Elisa De Franco
  • Khalid Hussain
Original Article


Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes resulting from mutations in more than 20 different genes encoding proteins playing a key role in the normal function of the pancreatic beta-cell. Mutations in the genes encoding the ATP-sensitive potassium channel, ABCC8, and KCNJ11 and insulin (INS) gene are the most common causes of NDM; however, in consanguineous populations, EIF2AK3 mutations are more common. Identification of the causative mutations by genetic testing is critical for appropriate management and to guide genetic counseling. To determine the genetic etiology of NDM in diabetic neonates and infants diagnosed before the age of 1 year and to describe their phenotype/genotype characteristics, DNA sequencing of coding regions and intronic boundaries of ABCC8, KCNJ11, INS, and EIF2AK3 genes was undertaken in 20 patients. Further, targeted next-generation sequencing was performed for other genes known to cause NDM. ABCC8 mutations were found in two patients (10%), with compound heterozygous mutations (p.N131 K/p.R598*) in one patient and a homozygous mutation (p.R1554Q) in the another patient. Heterozygous p.A174G and p.V59M mutations of KCNJ11 were identified in two patients (10%), and homozygous EIF2AK3 mutations were identified in two further patients (p.T905fs and p.R653T) (10%). No INS mutations were identified. Further testing identified a SLC19A2 mutation (p.W387*) in one patient (5%) and the same homozygous GCK mutation in two siblings (p.A188T). ABCC8, KCNJ11, and EIF2AK3 mutations were the main genetic causes of permanent NDM among Egyptian neonates.


NDM in Egypt Genetic screening ABBC8 KCNJ11 INS mutations 



This study was financially supported by the Egyptian Ministry of Higher Education-Culture Affairs and Missions Sector and by the Wellcome Trust. SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 105636/Z/14/Z).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from parents of all patients included in the study.


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Copyright information

© Research Society for Study of Diabetes in India 2018

Authors and Affiliations

  • Hanan Madani
    • 1
    Email author
  • Rasha Elkaffas
    • 1
    • 2
  • Badawy Alkholy
    • 1
  • Noha Musa
    • 3
  • Yomna Shaalan
    • 3
  • Rania Elkaffas
    • 3
  • Mona Hassan
    • 3
  • Mona Hafez
    • 3
  • Sarah E Flanagan
    • 4
  • Elisa De Franco
    • 4
  • Khalid Hussain
    • 2
    • 5
  1. 1.Clinical and chemical pathology department- Faculty of MedicineCairo UniversityCairoEgypt
  2. 2.UCL GOS Institute of Child HealthUCLLondonUK
  3. 3.Pediatric department- Faculty of MedicineCairo UniversityCairoEgypt
  4. 4.Institute of Biomedical and Clinical ScienceUniversity of Exeter Medical SchoolExeterUK
  5. 5.Sidra Medical & Research centerDohaQatar

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