{"id":11131,"date":"2026-03-04T00:00:00","date_gmt":"2026-03-04T00:00:00","guid":{"rendered":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1753969"},"modified":"2026-03-04T00:00:00","modified_gmt":"2026-03-04T00:00:00","slug":"defects-in-pdia4-increase-individuals-susceptibility-to-congenital-heart-disease","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/04\/defects-in-pdia4-increase-individuals-susceptibility-to-congenital-heart-disease\/","title":{"rendered":"Defects in PDIA4 increase individuals\u2019 susceptibility to congenital heart disease"},"content":{"rendered":"IntroductionCongenital heart disease (CHD) comprises structural abnormalities of the heart and major blood vessels arising during fetal development. Protein disulfide isomerase family member 4 (PDIA4) facilitates protein folding processes. However, its potential involvement in CHD has not been investigated. In this study, we identified PDIA4 as a candidate gene potentially involved in cardiac development.MethodsWhole-exome sequencing and targeted sequencing were performed to identify PDIA4 as a candidate gene of CHD. To investigate the functional role of PDIA4, PDIA4-knockdown human umbilical vein endothelial cells were generated, followed by cellular and transcriptomic analyses.ResultsA de novo PDIA4 mutation (NM004911: c.1249G>A: p.V417I) was found in a patient with complex CHD. Burden analysis demonstrated a significant enrichment of rare deleterious PDIA4 variants in patients with CHD compared with controls (Person\u2019s chi-squared test: OR: 4.08, 95% CI: 2.23\u20134.76, p = 7.46e\u22127). Deficiency of PDIA4 in human umbilical vein endothelial cells suppressed functionality and inhibited the protein levels of both total and nuclear \u03b2-catenin as well as the downstream activity of the WNT\/\u03b2-catenin signaling pathway.ConclusionOur study suggests that PDIA4 may act as a susceptibility gene for CHD, and its deficiency may contribute to abnormal cardiac development by modulating the WNT\/\u03b2-catenin signaling pathway.","protected":false},"excerpt":{"rendered":"<p>IntroductionCongenital heart disease (CHD) comprises structural abnormalities of the heart and major blood vessels arising during fetal development. Protein disulfide isomerase family member 4 (PDIA4) facilitates protein folding processes. However, its&#8230;<\/p>\n","protected":false},"author":461,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,12,13,82],"tags":[71],"class_list":["post-11131","post","type-post","status-publish","format-standard","hentry","category-articulos","category-enfermedades-raras","category-frontiers-in-genetics","category-original-research","tag-frontgenet"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/11131","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/461"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=11131"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/11131\/revisions"}],"predecessor-version":[{"id":11132,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/11131\/revisions\/11132"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=11131"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=11131"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=11131"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}