Genetic hallmarks of patients with congenital portosystemic shunts and portopulmonary hypertension: protocol for a multicentre exploratory study

Whole-genome sequencing in an international multicentre cohort of congenital portosystemic shunts aims to identify genetic variants linked to portopulmonary hypertension, which occurs in 7 to 14% of CPSS patients.

• Why it matters: PoPH is the most life-threatening manifestation of CPSS and may arise early in life, but paediatric PoPH genetics remain understudied.
• What they did: The study will perform international, registry-based whole-genome analysis of coding and non-coding regions in a predominantly paediatric CPSS cohort, using targeted checks of PAH/CHD/HHT/PoPH genes plus genome-wide discovery, with ACMG-based variant classification and trio/segregration analyses.
• The result: Findings are intended to improve personalised risk assessment and inform clinical decisions about elective shunt closure for individuals potentially at risk of developing PoPH.