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Loss-of-function variants in ciliary genes confer high risk for Tetralogy of Fallot

GSE295521 Mus musculus Expression profiling by high throughput sequencing 7 samples Submitted 2025/09/09 Platform GPL24247
Summary
Tetralogy of Fallot (TOF), the most common severe cyanotic congenital heart disease, has poorly understood genetic causes. Through next-generation sequencing in 131 nonsyndromic TOF patients, we identified an increased burden of rare deleterious variants in ciliary genes and cilium pathway, and observed a multigenic inheritance pattern, with an OR of 1.672 for more than two deleterious variants and a cumulative OR of 3.158 for six variants. Functional validation in single- and double-heterozygous mouse models carrying these variants recapitulated TOF-like phenotypes and impaired normal cilia structure and function, particularly disrupting Hedgehog signaling in cardiomyocytes, downregulating key transcription factors Gata4 and Nkx2-5.
Published in
Loss-of-function variants in ciliary genes confer high risk for tetralogy of Fallot
Zhou Y, Jiang T, Gao J et al. · Science advances 2025 · PMID 41071877 · doi:10.1126/sciadv.adt0836
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Also filed as BioProject PRJNA1255104 and SRA study SRP581008. Searching any of these in the dataset finder brings you back here.

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