Diabetes - neonatal onset

Gene: PDX1

Green List (high evidence)

PDX1 (pancreatic and duodenal homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000139515
EnsemblGeneIds (GRCh37): ENSG00000139515
OMIM: 600733, Gene2Phenotype
PDX1 is in 8 panels

3 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: Previous phenotypes:
Permanent neonatal diabetes;pancreas agenesis;permanent neonatal diabetes mellitus associated with pancreas agenesis;Pancreatic agenesis 1, 260370
Created: 3 Mar 2021, 2:32 p.m. | Last Modified: 3 Mar 2021, 2:32 p.m.
Panel Version: 2.24
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: PDX1; 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; panreatic agenesis.
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, 2:31 p.m.
Comment on list classification: Updated rating from Red to Green: 1 green expert review plus 3 unrelated cases supporting causation of neonatal diabetes due to pancreatic agenesis. Plus part of Exeter neonatal diabetes screen.
Created: 25 Apr 2017, 9:31 a.m.
PMID:2970316 (Schwitzgebel et al 2003) describe a compound heterozygote, with 2 point mutations in PDX1 (also called IPF1) leading to pancreas agenesis- each mutation was inherited from one parent.
Created: 25 Apr 2017, 9:30 a.m.
PMID:20009086 (Nocolino et al., 2010) identified a homozygous missesnse mutation (E178G) in PDX1 in a boy and girl, first cousins born of consanguineous parents, who had permanent neonatal diabetes mellitus. The 4 parents, who were all heterozygous for E178G, were asymptomatic and nondiabetic.
Created: 25 Apr 2017, 9:17 a.m.
Thomas et al. (PMID:19496967) report a family in which a male infant with pancreatic agenesis, whose parents were later determined to have MODY, was homozygous for the same 1-bp (188delC) deletion identified by PMID:8988180 (Stoffers et al., 1997): the authors suggest that the 2 families may be related.
Created: 25 Apr 2017, 9:17 a.m.
PMID:8988180 (Stoffers et al., 1997) report an infant presenting with neonatal diabetes mellitus at birth, who was homozygous for deletion of a single cytosine in codon 63 of the PDX1 gene (188delC), resulting in termination after 59 additional codons. The authors later reported (PMID:9326926) that homozygosity lead to pancreatic agenesis, whereas heterozygosity was associated with MODY4 (early-onset adult type II diabetes mellitus).
Created: 25 Apr 2017, 9:17 a.m.
Comment on mode of inheritance: Biallelic mode of inheritance supported by literature (PMID:8988180, PMID:9326926, PMID:20009086).
Created: 25 Apr 2017, 9:16 a.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
Phenotypes
  • Pancreatic agenesis 1, OMIM:260370
  • MODY, type IV, OMIM:606392
  • Permanent neonatal diabetes mellitus, MONDO:0100164
  • permanent neonatal diabetes mellitus associated with pancreas agenesis
OMIM
600733
Clinvar variants
Variants in PDX1
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: PDX1 were changed from Permanent neonatal diabetes; pancreas agenesis; permanent neonatal diabetes mellitus associated with pancreas agenesis; Pancreatic agenesis 1, 260370 to Pancreatic agenesis 1, OMIM:260370; MODY, type IV, OMIM:606392; Permanent neonatal diabetes mellitus, MONDO:0100164; permanent neonatal diabetes mellitus associated with pancreas agenesis

11 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to PDX1. 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 PDX1 were set to Permanent neonatal diabetes; pancreas agenesis; permanent neonatal diabetes mellitus associated with pancreas agenesis; Pancreatic agenesis 1, 260370

30 May 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for PDX1 were set to Permanent neonatal diabetes; pancreas agenesis; permanent neonatal diabetes mellitus associated with pancreas agenesis; Pancreatic agenesis 1, 260370;

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

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 Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for PDX1 were set to Permanent neonatal diabetes; pancreas agenesis; permanent neonatal diabetes mellitus associated with pancreas agenesis

25 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PDX1 were set to 8988180; 9326926; 19496967; 20009086; 2970316

25 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PDX1 were set to 8988180; 9326926; 19496967; 20009086

25 Apr 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for PDX1 was changed to BIALLELIC, autosomal or pseudoautosomal

17 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PDX1 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 PDX1 was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PDX1 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN