A novel NEUROG3 mutation in neonatal diabetes associated with a neuro-intestinal syndrome
| Autor: | Ayla Güven, Emmanuel Vaillant, Amélie Bonnefond, Franck De Graeve, J. Philippe, Suna Hancili, Philippe Froguel, Olivier Sand, Martine Vaxillaire, Jean-Jacques Robert, Kanetee Busiah, Michel Polak |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proband Biallelic Mutation Male endocrine system Endocrinology Diabetes and Metabolism Nonsense mutation 030209 endocrinology & metabolism Nerve Tissue Proteins Bioinformatics Diabetes Complications 03 medical and health sciences 0302 clinical medicine Neonatal diabetes mellitus Malabsorption Syndromes Diabetes mellitus Internal Medicine Basic Helix-Loop-Helix Transcription Factors Medicine Humans Child Genetics business.industry medicine.disease 030104 developmental biology Dysplasia Codon Nonsense Child Preschool Pediatrics Perinatology and Child Health Mutation (genetic algorithm) Female Age of onset business |
| Zdroj: | Pediatric diabetes. 19(3) |
| ISSN: | 1399-5448 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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