2026-04-29T04:09:20Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258182025-12-18T13:00:10Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Henderson, Deborah J author Alqahtani, Ahlam author Chaudhry, Bill author Cook, Andrew author Eley, Lorraine author Houyel, Lucile author Hughes, Marina author Keavney, Bernard author de la Pompa, José Luis author Sled, John author Spielmann, Nadine author Teboul, Lydia author Zaffran, Stephane author Mill, Pleasantine author Liu, Karen J author 2024-11-01 Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate. However, several other factors are likely to contribute. For example, the level of patient phenotyping required for clinical care may be insufficient for research studies focused on mechanistic discovery. Although several hundred mouse gene knockouts have been described with CHDs, these are generally not phenotyped and described in the same way as CHDs in patients, and thus are not readily comparable. Moreover, most patients with CHDs carry variants of uncertain significance of crucial cardiac genes, further complicating comparisons between humans and mouse mutants. In spite of major advances in cardiac developmental biology over the past 25 years, these advances have not been well communicated to geneticists and cardiologists. As a consequence, the latest data from developmental biology are not always used in the design and interpretation of studies aimed at discovering the genetic causes of CHDs. In this Special Article, while considering other in vitro and in vivo models, we create a coherent framework for accurately modelling and phenotyping human CHDs in mice, thereby enhancing the translation of genetic and genomic studies into the causes of CHDs in patients. Dis Model Mech. 2024 Nov 1;17(11):dmm050913. https://hdl.handle.net/20.500.12105/25818 39575509 Disease Models and Mechanisms Cardiac phenotyping Congenital heart defect Developmental biology Disease modelling Gene variant Genetics Genomics Human patient Mouse model Structural anomalies Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping.