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

作者：Hancili Suna; Bonnefond Amelie; Philippe Julien; Vaillant Emmanuel; De Graeve Franck; Sand Olivier; Busiah Kanetee; Robert Jean Jacques; Polak Michel; Froguel Philippe; Guven Ayla^*; Vaxillaire Martine^*

来源：Pediatric Diabetes, 2018, 19(3): 381-387.

DOI：10.1111/pedi.12576

• neonatal diabetes mellitus
• NEUROG3
• neurogenin-3
• neurointestinal syndrome
• recessive mutation

Neonatal diabetes mellitus (NDM) is a rare form of non-autoimmune diabetes usually diagnosed in the first 6months 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.

• 出版日期2018-5