Related Experiment Video

Updated: Mar 20, 2026

Analysis of Congenital Heart Defects in Mouse Embryos Using Qualitative and Quantitative Histological Methods
08:28

Analysis of Congenital Heart Defects in Mouse Embryos Using Qualitative and Quantitative Histological Methods

Published on: March 10, 2020

7.4K

Defects in PDIA4 increase individuals' susceptibility to congenital heart disease

Yuquan Lu1,2, Jiangjie Liu1,2, Siyu Sun1,2

  • 1Pediatric Heart Center, Children's Hospital of Fudan University, Shanghai, China.

Frontiers in Genetics
|March 19, 2026
PubMed

Insights

Protein disulfide isomerase family member 4 (PDIA4) is implicated in congenital heart disease (CHD). PDIA4 deficiency impairs cardiac development by affecting the WNT/β-catenin pathway.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • Congenital heart disease (CHD) involves structural heart defects during fetal development.
  • The role of Protein disulfide isomerase family member 4 (PDIA4) in CHD is unexplored.
  • PDIA4 is known to facilitate protein folding.

Purpose of the Study:

  • To investigate the potential involvement of PDIA4 in congenital heart disease.
  • To identify PDIA4 as a candidate gene for CHD.
  • To elucidate the functional role of PDIA4 in cardiac development.

Main Methods:

  • Whole-exome and targeted sequencing identified PDIA4 as a candidate gene.
  • PDIA4-knockdown human umbilical vein endothelial cells were generated.
  • Cellular and transcriptomic analyses were performed.

Main Results:

  • A de novo PDIA4 mutation was identified in a patient with complex CHD.
  • Rare deleterious PDIA4 variants were significantly enriched in CHD patients.
  • PDIA4 deficiency suppressed endothelial cell function and WNT/β-catenin signaling.

Conclusions:

  • PDIA4 may serve as a susceptibility gene for CHD.
  • PDIA4 deficiency can contribute to abnormal cardiac development.
  • Modulation of WNT/β-catenin signaling by PDIA4 is crucial for cardiac development.
Abstract

Keywords:
congenital heart diseaseprotein disulfide isomerase family member 4targeted sequencingvariantswhole-exome sequencingwnt/β-catenin signaling pathway

More Related Videos

Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound 30/45MHZ System07:34

Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound 30/45MHZ System

Published on: May 5, 2018

12.5K
A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse08:19

A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse

Published on: December 16, 2022

2.5K

Related Concept Videos

Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
640
Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
4.4K
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
727
Rheumatic Heart Disease I: Introduction01:23

Rheumatic Heart Disease I: Introduction

Rheumatic heart disease or RHD is a chronic condition that results from rheumatic fever, causing permanent damage to the heart valves.Etiology and Risk FactorsIt primarily arises from rheumatic fever, an inflammatory disease that can develop after untreated or inadequately treated group A streptococcal (GAS) pharyngitis. Streptococcus spreads through direct contact with oral or respiratory secretions. While the bacteria are the causative agents, factors like malnutrition, overcrowding, poor...
775
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
746
Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
1.5K