Neonatal diabetes
Gene: IL2RA
Comment on phenotypes: Previous phenotypes:
neonatal diabetes;insulin-dependent diabetes mellitus at 8-weeks;IPEX-like syndrome;{Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942;Neoantal diabetes, congenital hypothyrodism (multiple autoimmune) RecessiveCreated: 3 Mar 2021, 1:33 p.m. | Last Modified: 3 Mar 2021, 1:33 p.m.
Panel Version: 2.15
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: IL2RA; 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: Neoantal diabetes, congenital hypothyrodism (multiple autoimmune) Recessive.Created: 11 Jan 2019, 4:27 p.m.
Neonatal diabetes has been reported in 1/4 patients with IL2RA mutations in the paper by Caudy et al 2007 J Allergy Clin Immunol. 119:482-7. We have also identified mutations in this gene in 2 additional unrelated patients referred to Exeter for neonatal diabetes testing.Created: 29 May 2017, 8:34 a.m.
Publications
Comment on list classification: Updated rating from Grey to Green. IL2RA gene added by Sian Ellard during panel review. PMID:17196245 (Caudy et al 2007) report 1 patient with neonatal diabetes and biallelic IL2RA mutations. Elisa De-Franco (University of Exeter Medical School) report 2 additional patients referred to Exeter for referred to Exeter for neonatal diabetes testing. Therefore 3 cases in total, plus part of Exeter neonatal diabetes screen.Created: 30 May 2017, 3:30 p.m.
Comment when marking as ready: Marked as Ready: 29th May 2017.Created: 29 May 2017, 7:53 a.m.
Comment on mode of inheritance: Biallelic mode of inheritance supported by patient reported in PMID:17196245 (Caudy et al., 2007).Created: 25 May 2017, 8:44 a.m.
PMID:17196245 (Caudy et al., 2007) describe a patient with an IPEX-like syndrome (including insulin-dependent diabetes mellitus diagnosed at 6 weeks), and a deficiency in CD25 (IL2RA). He carries a single base pair insertion of one allele of his CD25 gene and a second allele with a substitution resulting in a stop codon. Paper was highlighted by Dr. Elisa De, Franco, University of Exeter Medical School.Created: 25 May 2017, 8:43 a.m.
Phenotypes for gene: IL2RA were changed from neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942; Neoantal diabetes, congenital hypothyrodism (multiple autoimmune) Recessive to neonatal diabetes mellitus, MONDO:0016391; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, OMIM:601942; neonatal diabetes mellitus with congenital hypothyroidism, MONDO:0012436
Phenotypes for gene: IL2RA were changed from neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942 to neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942; Neoantal diabetes, congenital hypothyrodism (multiple autoimmune) Recessive
Source NHS GMS was added to IL2RA. 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.
Phenotypes for IL2RA were set to neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome; {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of inheritance for IL2RA was changed to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for IL2RA were set to neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks; IPEX-like syndrome
Publications for IL2RA were set to 17196245
Phenotypes for IL2RA were set to neonatal diabetes; insulin-dependent diabetes mellitus at 8-weeks;
IL2RA was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Expert Review