Neonatal diabetes
Gene: NEUROG3
Comment on phenotypes: Previous phenotypes:
Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes; Syndromic neonatal diabetes with malabsorptive diarrhea (neurointestinal dysplasia, intrahepatic bilary tract, abnormalities of thyroid gland and CNS)
Permanent neonatal diabetes mellitus, MONDO:0100164;
Diarrhea 4, malabsorptive, congenital, OMIM:610370Created: 3 Mar 2021, 2:26 p.m. | Last Modified: 3 Mar 2021, 2:26 p.m.
Panel Version: 2.22
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: NEUROG3; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Syndromic neonatal diabetes with malabsorptive diarrhea (neurointestinal dysplasia, intrahepatic bilary tract, abnormalities of thyroid gland and CNS).Created: 11 Jan 2019, 4:27 p.m.
A further patient was reported by Rubio-Cabezas et al 2014 Diabetologia.Created: 29 May 2017, 8:34 a.m.
Publications
Comment when marking as ready: Marked as Ready: 29th May 2017.Created: 29 May 2017, 8:41 a.m.
Comment on list classification: Updated rating from Red to Green: Green expert review plus 3 published cases.Created: 29 May 2017, 8:41 a.m.
Greeley et al., review (PMID: 21993633) note that 3 patients originally reported with isolated diarrhea due to missense mutations in NEUROG3 (originally reported by Wang et al., 2006, PMID:16855267), later also developed insulin-requiring diabetes by 9 years of age.Created: 23 May 2017, 3:14 p.m.
Comment on mode of inheritance: Biallelic mode of inheritance supported by literature (PMID:21378176, PMID:21490072).Created: 25 Apr 2017, 7:57 a.m.
PMID:21490072 (Pinnet et al., 2011) report a proband with neonatal diabetes and congenital malabsorptive diarrhea, with a novel homozygous nonsense mutation (E123X) in NEUROG3.Created: 25 Apr 2017, 7:57 a.m.
PMID:21378176 (Rubio-Cabezas et al., 2011) identified 2 compound heterozygous point mutations in NEUROG3 in a proband with permanent neonatal diabetes [c.82G>T (p.E28X) and c.404T>C (p.L135P)], each being inherited from an unaffected parent.Created: 24 Apr 2017, 3:02 p.m.
Phenotypes for gene: NEUROG3 were changed from Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes; Syndromic neonatal diabetes with malabsorptive diarrhea (neurointestinal dysplasia, intrahepatic bilary tract, abnormalities of thyroid gland and CNS) to Permanent neonatal diabetes mellitus, MONDO:0100164; Diarrhea 4, malabsorptive, congenital, OMIM:610370
Phenotypes for gene: NEUROG3 were changed from Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes to Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes; Syndromic neonatal diabetes with malabsorptive diarrhea (neurointestinal dysplasia, intrahepatic bilary tract, abnormalities of thyroid gland and CNS)
Source NHS GMS was added to NEUROG3. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted panel to Version 1: 31st May 2017. This panel is largely aligned with the Exeter Molecular Genetics Laboratory neonatal diabetes screen. Note that 8 genes feature on the Exeter 8-gene panel for patients with 'neonatal diabetes and autoimmune disease' (FOXP3, IL2RA, ITCH, LRBA, SIRT1, STAT1, STAT3 and STAT5). ITCH, SIRT1, STAT1 and STAT5A/B do not feature on this panel following correspondance with Elisa De-Franco (University of Exeter Medical School) that, at the time of curation, none of the patients with mutations in ITCH, SIRT1, STAT1 and STAT5b had diabetes diagnosed in the neonatal period, and therefore there is currently insufficient evidence to include these genes in this neonatal diabetes panel.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for NEUROG3 were set to 21378176; 21490072; 21993633; 25120094
Publications for NEUROG3 were set to 21378176; 21490072; 21993633
Phenotypes for NEUROG3 were set to Permanent neonatal diabetes and enteric anendocrinosis; congenital malabsorptive diarrhea and neonatal diabetes
Publications for NEUROG3 were set to 21378176; 21490072
Mode of inheritance for NEUROG3 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for NEUROG3 were set to 21378176
NEUROG3 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing
Model of inheritance for gene NEUROG3 was changed to BIALLELIC, autosomal or pseudoautosomal
NEUROG3 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN