Diabetes - neonatal onset

Gene: HNF1B

Green List (high evidence)

HNF1B (HNF1 homeobox B)
EnsemblGeneIds (GRCh38): ENSG00000275410
EnsemblGeneIds (GRCh37): ENSG00000108753
OMIM: 189907, Gene2Phenotype
HNF1B is in 22 panels

4 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: Previous phenotypes:
Transient neonatal diabetes;transient neonatal diabetes mellitus (TNDM);permanent neonatal diabetes mellitus;Diabetes mellitus, noninsulin-dependent, 125853;Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW
Created: 3 Mar 2021, 1:25 p.m. | Last Modified: 3 Mar 2021, 1:25 p.m.
Panel Version: 2.13
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: HNF1B; 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: Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW.
Created: 11 Jan 2019, 4:27 p.m.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

Elisa De Franco (University of Exeter Medical School)

We have 2 additional cases that have been identified by our lab.
Created: 29 May 2017, 8:34 a.m.

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as Ready: 29th May 2017.
Created: 29 May 2017, 8:36 a.m.
Comment on list classification: Updated rating from Red to Green: 2 published cases supporting gene:disease association (Yorifuji and Edghill), and 2 further cases reported by Dr Elisa De Franco as part of Exeter neonatal diabetes screen.
Created: 29 May 2017, 8:36 a.m.
PMID:15181075 (Yorifuji et al, 2004) describe a missense mutation in HNF1B (C443G, S148W) in two siblings: one with neonatal diabetes mellitus and one with neonatal polycystic, dysplastic kidneys (with transient hyperglycemia which resolved spontaneously). This is the first report of permanent neonatal diabetes caused by a mutation of HNF1B.
Created: 24 Apr 2017, 9:51 a.m.
Comment on mode of inheritance: Monoallelic mode of inheritance supported by literature.
Created: 24 Apr 2017, 9:42 a.m.
PMID:17116179 (Edghill et al., 2006) identified a heterozygous S148L HNF1B mutation in one patient with neonatal diabetes diagnosed at 17 days.
Created: 24 Apr 2017, 9:40 a.m.
Added 'mosaicism' tag based on PMID:15181075 (Yorifuji et al) which showed germline mosaicism of HNF1B; the unaffected mother was a low-level mosaic of normal and mutant HNF1B.
Created: 24 Apr 2017, 9:24 a.m.

Details

History Filter Activity

3 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: HNF1B were changed from Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus; Diabetes mellitus, noninsulin-dependent, 125853; Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW to Transient neonatal diabetes mellitus (disease), MONDO:0020525; permanent neonatal diabetes mellitus, MONDO:0100164; Type 2 diabetes mellitus, OMIM:125853; transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW

15 Jul 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: HNF1B were changed from Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus; Diabetes mellitus, noninsulin-dependent, 125853 to Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus; Diabetes mellitus, noninsulin-dependent, 125853; Transient neonatal diabetes, pancreatic atrophy, mild exocrine insufficiency and low BW

11 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to HNF1B. 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.

30 May 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HNF1B were set to Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus; Diabetes mellitus, noninsulin-dependent, 125853

29 May 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).

29 May 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).

24 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HNF1B were set to 15181075; 26997508; 17116179; 16207896; 21993633; 15930087

24 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HNF1B were set to Transient neonatal diabetes; transient neonatal diabetes mellitus (TNDM); permanent neonatal diabetes mellitus

24 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HNF1B were set to 15181075; 26997508; 17116179; 16207896; 21993633

24 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HNF1B were set to Transient neonatal diabetes; permanent neonatal diabetes mellitus

24 Apr 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for HNF1B was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HNF1B were set to 15181075; 26997508; 17116179; 16207896

24 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HNF1B were set to 15181075; 26997508; 17116179

24 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HNF1B were set to Transient neonatal diabetes; Diabetes mellitus, noninsulin-dependent, 125853; permanent neonatal diabetes mellitus

24 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HNF1B were set to Transient neonatal diabetes; Diabetes mellitus, noninsulin-dependent, 125853; neonatal diabetes mellitus

24 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HNF1B were set to Transient neonatal diabetes; Diabetes mellitus, noninsulin-dependent, 125853

24 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HNF1B were set to 15181075

17 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

HNF1B 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 HNF1B was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

17 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

HNF1B was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN