Pulmonology · Cardiology · 3 h ago
Rare FOXF1 Coding Variants Associated With Pulmonary Arterial Hypertension
Genomic analyses of three independent international pulmonary arterial hypertension cohorts identified rare FOXF1 variants, alongside reduced endothelial FOXF1 expression in affected lungs. Laboratory experiments supported BMPR2 as a potential downstream transcriptional target; cohort sizes were not reported in the available abstract.
- Three international PAH cohorts were screened for deleterious FOXF1 variants.
- FOXF1 expression was reduced in PAH endothelial cells.
- Laboratory assays supported FOXF1-dependent transcriptional regulation of BMPR2.
- Clinical utility for genetic testing remains unestablished.
A genomic and functional study examined FOXF1 alterations in pulmonary arterial hypertension (PAH), following identification of ultra-rare missense variants in two index cases. Researchers screened three independent international PAH cohorts for predicted deleterious variants and assessed lung FOXF1 expression using bulk and single-cell RNA sequencing and immunofluorescence. The available abstract does not specify cohort sizes.
Across the cohorts, investigators identified nine novel and one rare missense variants, one start-site variant, and one in-frame deletion. FOXF1 expression was reduced in PAH lungs and localized predominantly to endothelial cells, with the lowest levels in phenotypically abnormal endothelial cells within complex vascular lesions. Single-cell analyses confirmed reduced endothelial expression in PAH; broad downregulation across endothelial populations was not observed in other chronic lung diseases.
Chromatin profiling identified a canonical FOXF1-binding motif within the BMPR2 promoter. In vitro promoter-reporter assays supported FOXF1-dependent regulation of BMPR2 and showed reduced transcriptional activity of PAH-associated FOXF1 variants. These findings support an association between FOXF1 dysregulation and PAH and suggest a potential regulatory link to BMPR2. They do not establish clinical utility for FOXF1 testing or treatment selection. Interpretation is limited by abstract-only access and the absence of reported cohort sizes or quantitative association estimates.
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American Journal of Respiratory and Critical Care Medicine: Rare Coding Variants in FOXF1 are Associated with Pulmonary Arterial Hypertension ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.