A novel NEUROG3 mutation in neonatal diabetes associated with a neuro-intestinal syndrome

Pediatr Diabetes. 2018 May;19(3):381-387. doi: 10.1111/pedi.12576. Epub 2017 Sep 22.


Neonatal diabetes mellitus (NDM) is a rare form of non-autoimmune diabetes usually diagnosed in the first 6 months of life. Various genetic defects have been shown to cause NDM with diverse clinical presentations and variable severity. Among transcriptional factor genes associated with isolated or syndromic NDM, a few cases of homozygous mutations in the NEUROG3 gene have been reported, all mutated patients presenting with congenital malabsorptive diarrhea with or without diabetes at a variable age of onset from early life to childhood. Through a targeted next-generation sequencing assay for monogenic diabetes genes, we aimed to search for pathogenic deleterious mutation in a Turkish patient with NDM, severe malabsorptive diarrhea, neurointestinal dysplasia and other atypical features. In this patient, we identified a novel homozygous nonsense mutation (p.Q4*) in NEUROG3. The same biallelic mutation was found in another affected family member. Of note, the study proband presents with abnormalities of the intrahepatic biliary tract, thyroid gland and central nervous system, which has never been reported before in NEUROG3 mutation carriers. Our findings extend the usually described clinical features associated with NEUROG3 deficiency in humans, and question the extent to which a complete lack of NEUROG3 expression may affect pancreas endocrine function in humans.

Keywords: NEUROG3; neonatal diabetes mellitus; neurogenin-3; neurointestinal syndrome; recessive mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Child
  • Child, Preschool
  • Codon, Nonsense
  • Diabetes Complications / genetics*
  • Female
  • Humans
  • Malabsorption Syndromes / complications
  • Malabsorption Syndromes / genetics*
  • Male
  • Nerve Tissue Proteins / genetics*


  • Basic Helix-Loop-Helix Transcription Factors
  • Codon, Nonsense
  • NEUROG3 protein, human
  • Nerve Tissue Proteins