FBLN2 – Pulmonary arterial hypertension

Fibulin-2 (FBLN2) has been implicated as a novel risk gene for Pulmonary arterial hypertension through a large-scale rare variant association study. In 1647 idiopathic PAH cases and 18 819 controls, rare deleterious missense variants in FBLN2 reached a false discovery rate <0.1, with multiple unrelated probands carrying variants in conserved domains (PMID:33971972). No familial segregation data were reported, and replication in independent cohorts remains outstanding. Expression profiling showed FBLN2 is expressed in lung and heart tissues in patterns similar to established PAH genes, supporting biological plausibility, but no functional assays in PAH models have yet been performed. Taken together, the association meets a Limited level of clinical validity under ClinGen criteria, reflecting initial statistical support without segregation or mechanistic follow-up. Key take-home: FBLN2 is a promising candidate for PAH risk, but further genetic and functional studies are needed to inform diagnostic use.

References

• Genome Medicine • 2021 • Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH. PMID:33971972

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