Diabetes - neonatal onset

Gene: RFX6

Green List (high evidence)

RFX6 (regulatory factor X6)
EnsemblGeneIds (GRCh38): ENSG00000185002
EnsemblGeneIds (GRCh37): ENSG00000185002
OMIM: 612659, Gene2Phenotype
RFX6 is in 10 panels

3 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

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 syndrome
Created: 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.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

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.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
Phenotypes
  • Mitchell-Riley syndrome, OMIM:615710 (includes neonatal diabetes)
OMIM
612659
Clinvar variants
Variants in RFX6
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

3 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

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)

15 Jul 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

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

11 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to RFX6. Rating Changed from Green List (high evidence) to Green List (high evidence)

31 May 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

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.

25 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

25 Apr 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for RFX6 was changed to BIALLELIC, autosomal or pseudoautosomal

25 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

25 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RFX6 were set to 21215266; 21965172; 20148032; 26264437

25 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for RFX6 were set to Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities; Mitchell-Riley syndrome, 615710 (includes neonatal diabetes)

25 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RFX6 were set to 21965172; 20148032; 21215266

17 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

RFX6 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing

17 Aug 2015, Gel status: 1

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene RFX6 was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

RFX6 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN