Neonatal diabetes
Gene: RFX6
Comment on phenotypes: Previous phenotypes:
Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities;Mitchell-Riley syndrome, 615710 (includes neonatal diabetes);Syndromic Neonatal diabetes;pancreatic hypoplasia, gallbladder aplasia and intestinal atresia;Mitchell-Riley syndromeCreated: 3 Mar 2021, 2:36 p.m. | Last Modified: 3 Mar 2021, 2:36 p.m.
Panel Version: 2.26
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: RFX6; 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; pancreatic hypoplasia, gallbladder aplasia and intestinal atresia; Mitchell-Riley syndrome.Created: 11 Jan 2019, 4:27 p.m.
Comment when marking as ready: Marked as Ready: April 25th 2017.Created: 25 Apr 2017, 2:32 p.m.
Comment on mode of inheritance: Biallelic mode of inheritance supported by OMIM and literature.Created: 25 Apr 2017, 10 a.m.
Comment on list classification: Updated rating from Red to Green: 1 green expert review plus >3 unrelated cases of RFX6 mutations causing Mitchell-Riley syndrome/neonatal diabetes. Plus part of Exeter neonatal diabetes screen.Created: 25 Apr 2017, 9:58 a.m.
Smith et al. (2010, PMID:20148032) analyzed the candidate gene RFX6 in 6 patients with neonatal diabetes, hypoplastic or annular pancreas, intestinal atresia and/or malrotation, and gallbladder hypoplasia or agenesis (Mitchell-Riley syndrome, MIM:615710), and identified homozygosity or compound heterozygosity for RFX6 mutations in 5 of the 6 probands.Created: 25 Apr 2017, 9:56 a.m.
PMID:21965172 (Spiegel et al., 2011) summarises 7 patients (including a new patient to this publication) with neonatal diabetes and homozygous RFX6 mutations.Created: 25 Apr 2017, 9:56 a.m.
Phenotypes for gene: RFX6 were changed from Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes); Syndromic Neonatal diabetes; pancreatic hypoplasia, gallbladder aplasia and intestinal atresia; Mitchell-Riley syndrome to Mitchell-Riley syndrome, OMIM:615710 (includes neonatal diabetes)
Phenotypes for gene: RFX6 were changed from Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes) to Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes); Syndromic Neonatal diabetes; pancreatic hypoplasia, gallbladder aplasia and intestinal atresia; Mitchell-Riley syndrome
Source NHS GMS was added to RFX6. 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).
Mode of inheritance for RFX6 was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
Publications for RFX6 were set to 21215266; 21965172; 20148032; 26264437
Phenotypes for RFX6 were set to Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes)
Publications for RFX6 were set to 21965172; 20148032; 21215266
RFX6 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing
Model of inheritance for gene RFX6 was changed to BIALLELIC, autosomal or pseudoautosomal
RFX6 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN