Mutations in VCP cause Adams-Oliver syndrome with or without pulmonary hypertension - PubMed
5 hours ago
- #pulmonary hypertension
- #VCP mutations
- #Adams-Oliver syndrome
- Mutations in VCP are identified as a new genetic cause of Adams-Oliver syndrome (AOS), both with and without pulmonary hypertension (PH).
- AOS-related VCP variants are hypermorphic, increasing ATP hydrolysis, causing N-terminal domain hyperflexibility and impairing interdomain coupling.
- PH in AOS often involves pulmonary veno-occlusive disease, with clinical risk factors including CMTC, dilated subcutaneous veins, and intra-uterine growth restriction.
- The VCP inhibitor CB-5083 can inhibit the overactive ATP hydrolysis of these variants, suggesting a potential therapeutic approach.
- This finding provides the prevalent genetic explanation for PH in AOS cases previously lacking a diagnosis.