DEMO Diabetes neonatal onset
Gene: PDX1
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.
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.
Comment on mode of inheritance: As suggested by reviewer.Created: 7 Jun 2016, 9:39 a.m.
Comment on list classification: Promoted from amber to green due to expert review. Multiple reports in OMIM, for different variants.Created: 7 Jun 2016, 9:36 a.m.
gene: PDX1 was added gene: PDX1 was added to DEMO Diabetes - neonatal onset. Sources: Expert Review Green,NHS GMS,Eligibility statement prior genetic testing,UKGTN Mode of inheritance for gene: PDX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDX1 were set to 2970316; 20009086; 8988180; 19496967; 9326926 Phenotypes for gene: PDX1 were set to pancreas agenesis; Permanent neonatal diabetes; permanent neonatal diabetes mellitus associated with pancreas agenesis; Pancreatic agenesis 1, 260370