Evidence map›Paper›PMID 40485586›Full record

ArticleJCI insight2025

Neonatal diabetes-associated missense PDX1 variant disrupts chromatin association and protein-protein interaction.

Xiaodun Yang, Angela Zanfardino, Riccardo Schiaffini, Jeff Ishibashi, Bareket Daniel, Matthew W Haemmerle, Novella Rapini, Alessia Piscopo, Emanuele Miraglia Del Giudice, Maria Cristina Digilio and 6 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Xiaodun YangInstitute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Angela ZanfardinoRegional Center for Pediatric Diabetes, Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy.
Riccardo SchiaffiniDiabetology and Growth Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Jeff IshibashiInstitute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Bareket DanielInstitute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Matthew W HaemmerleInstitute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Novella RapiniDiabetology and Growth Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Alessia PiscopoRegional Center for Pediatric Diabetes, Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy.
Emanuele Miraglia Del GiudiceDepartment of Pediatrics, University of Campania "Luigi Vanvitelli," Caserta CE, Italy.
Maria Cristina DigilioMedical Genetics Unit and Medical Genetics and Rare Disease Research Division, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Raffaele IorioDepartment of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
Mafalda MuccioloTranslational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Stefano CianfaraniDiabetology and Growth Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Dario IafuscoRegional Center for Pediatric Diabetes, Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy.
Fabrizio BarbettiClinical Laboratory Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Doris A StoffersInstitute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Patrick Seale · 1986 to 2026
$48.3M
Functional interaction of transcriptional regulators in endocrine lineage specificationR01DK135032 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Maureen A Gannon, DORIS A STOFFERS · 2023 to 2026
$2.8M
A stress inducible Pdx1 transcriptional complex governing beta cell survivalR01DK121175 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI STOFFERS, DORIS A · 2019 to 2023
$2.3M
Role of the RNA-binding, polyC-binding proteins in pancreatic beta cellsR01DK122039 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI STOFFERS, DORIS A · 2019 to 2022
$1.8M
NCI NIH HHS P30 CA016520NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK121175NIDDK NIH HHS R01 DK122039NIDDK NIH HHS R01 DK135032
6 · The paper itself

Abstract

PDX1 mutations are associated with multiple forms of diabetes, including syndromic, neonatal, mature onset diabetes of the young (MODY), and type 2 diabetes. Two PDX1 missense mutations (Thr151Met and Asn196Thr) were identified in a pediatric female patient that cause permanent neonatal diabetes, pancreas hypoplasia, and a malformed gallbladder. We found that the mouse Pdx1 Asn197Thr variant (homologous to human PDX1 Asn196Thr), but not Pdx1 Thr152Met (homologous to human PDX1 Thr151Met), altered its nuclear localization and disrupted the PDX1-ONECUT1 interaction. Neither variant substantially affected PDX1 protein stability, but both reduced PDX1 binding to the Pdx1 gene promoter. Importantly, the Pdx1 Asn197Thr variant caused pancreas agenesis and reduced enteroendocrine cells in the duodenum in genetically engineered mice, due at least in part to reduced Pdx1 promoter binding and disrupted PDX1-ONECUT1 interaction.

Indexed as

ChromatinDiabetes MellitusDiabetes Mellitus, Type 2Homeodomain ProteinsMutation, MissenseTrans-ActivatorsAnimalsFemaleHumansInfant, NewbornInfant, Newborn, DiseasesMicePancreasPromoter Regions, GeneticProtein BindingChromatinHomeodomain Proteinspancreatic and duodenal homeobox 1 proteinTrans-ActivatorsDevelopmentDiabetesEndocrinologyGenetic diseases

Identifiers

PMID40485586
PMCPMC12220937

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.