Neonatal diabetes
Gene: GATA4
Comment on phenotypes: Previous phenotypes:
Neonatal diabetes, Pancreatic agenesis and/or congenital heart defects;permanent neonatal diabetes melllitus;transient neonatal diabetes melllitusCreated: 3 Mar 2021, 1:09 p.m. | Last Modified: 3 Mar 2021, 1:09 p.m.
Panel Version: 2.9
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: GATA4; 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: neonatal diabetes and congenital heart defects.Created: 11 Jan 2019, 4:27 p.m.
After the first report of 2 patients with neonatal diabetes, we now have identified 2 further patients with neonatal diabetes and a spontaneous GATA4 deletion.Created: 29 May 2017, 8:34 a.m.
Comment when marking as ready: Marked as ready: May 30th 2017.Created: 30 May 2017, 9:44 a.m.
Comment on list classification: Updated rating from Red to Green: Expert reviewed green plus >3 cases of GATA4 deletions (publications plus further cases reported by Elisa de Franco). GATA4 is also green on multiple other diabetes panels.Created: 30 May 2017, 9:44 a.m.
PMID:20854389 (D'Amato et al., 2010) find a GATA (c1512C>T) mutation in a patient with pancreatic agenesis and an atrial septal defect. However, in family members, the GATA4 mutation co-segregated with a cardiac phenoptype, but not with pancreatic agenesis, and the authors conclude that the pancreatic agenesis may be due to an alternative independent event.Created: 24 Apr 2017, 8:41 a.m.
PMID:24696446 (Shaw-Smith et al., 2014) report 4 patients with diabetes in the neonatal period and deletions (17Mb , 15 Mb and 1Mb) or mutation (missense c819C>A, p.N273K) in the GATA4 gene. All the deletions span multiple genes.Created: 20 Apr 2017, 1:18 p.m.
Added 'deletions' tag, based on deletions reported in PMID:24696446 (Shaw-Smith et al., 2014).Created: 20 Apr 2017, 1:13 p.m.
Phenotypes for gene: GATA4 were changed from Neonatal diabetes, Pancreatic agenesis and/or congenital heart defects; permanent neonatal diabetes melllitus; transient neonatal diabetes melllitus to Pancreatic hypoplasia-diabetes-congenital heart disease syndrome, MONDO:0010802; permanent neonatal diabetes melllitus, MONDO:0100164; Transient neonatal diabetes mellitus (disease), MONDO:0020525
Source NHS GMS was added to GATA4. 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.
Mode of inheritance for GATA4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for GATA4 were set to 24696446; 20854389; 27810688
Phenotypes for GATA4 were set to Neonatal diabetes, Pancreatic agenesis and/or congenital heart defects; permanent neonatal diabetes melllitus; transient neonatal diabetes melllitus
Publications for GATA4 were set to 24696446; 20854389
Publications for GATA4 were set to 24696446
GATA4 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing
Model of inheritance for gene GATA4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
GATA4 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN