Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension

NCT07314814 | Not Yet Recruiting

• 1 other identifier: 2024-01698
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Congenital portosystemic shunt (CPSS) are rare vascular malformations causing blood from the intestines to bypass the liver and directly flow into body's general circulation. Such liver bypass can cause several health problems, one of the most severe being portopulmonary hypertension (PoPH). The goal of this study is to identify pathogenic and potentially pathogenic genetic variants in patients who have both CPSS and PoPH. Future research will assess the contribution of these genetic variants to the development of PoPH. The long-term goal is to use genetic information to identify patients with congenital portosystemic shunts (CPSS) or chronic liver disease who are at risk of developing PoPH to offer anticipatory management. Children and adult patients with both CPSS and PoPH, as well as their close relatives (patient's parents and siblings) can take part in the study. Genetic variations within each family will be studied.

Conditions

Portopulmonary Hypertension; Pulmonary Arterial Hypertension (PAH); Congenital Portosystemic Shunt

Keywords

CPSS; PoPH; PAH; Genetic; Genomic; IRCPSS

Outcome Measures

Primary Outcomes (2)

• List of variants from targeted analysis of selected gene panels

  presence/absence of pathogenic variants in known genes (pulmonary arterial hypertension ; hereditary hemorrhagic telangiectasia ; congenital heart disease) and potentially pathogenic variants in genes previously associated with PoPH in cirrhosis cohort.

  From February 2026 to February 2029

• List of variants from whole genome analysis

  variants identified using family based search for dominant or recessive potentially pathogenic variants

  Fron February 2026 to August 2029

Study Arms (1)

30 families

patient + parents+ siblings

Genetic: targeted gene panels analysis; Genetic: whole genome analysis

Interventions

targeted gene panels analysis GENETIC

The following gene panels will be analyzed : pulmonary arterial hypertension ; hereditary hemorrhagic telangiectasia ; congenital heart disease and potentially pathogenic variants in genes previously associated with PoPH in cirrhosis cohort.

30 families

whole genome analysis GENETIC

Family-based identification of dominant or recessive potentially pathogenic variants.

30 families

Eligibility Criteria

• Age: 1 Day - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient participant in the IRCPSS, with history of CPSS and PoPH ; both parents of the patient participants; possibly patient siblings.

You may qualify if:

• Patient is a participant to the IRCPSS with history of PoPH
• Trios composed of CPSS PoPH patients and their parents (trios are mandatory)
• Brother/sister of an enrolled patient
• Trios accept to provide biological samples (blood), sign the inform consent.
• Siblings and/or siblings' legal representatives accept to provide biological samples (blood), sign the inform consent.

You may not qualify if:

• Trio condition is not met.
• No genuine parent-offspring trios (check for medically assisted procreation with donors, and adoption)
• For siblings, half-brothers or half-sisters are excluded, as well as adopted children, or children issued from medically assisted procreation with donors.
• Secondary portosystemic shunts
• The refusal by the patient or the patient's legal representatives to provide biological samples or agree with the proposed procedure or after voluntary withdrawal from the project.
• The refusal of one of the parents to provide biological samples or to agree with the proposed procedure or after voluntary withdrawal from the project.

Sponsors & Collaborators

• Prof. Valérie Mc Lin: lead

Study Sites (1)

University Hospitals Geneva / University of Geneva

Geneva, Canton of Geneva, 1205, Switzerland

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample -\> genomic DNA

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Congenital Portosystemic Shunt

Interventions

Genome-Wide Association Study

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Molecular Epidemiology; Genetic Association Studies; Genetic Techniques; Oligonucleotide Array Sequence Analysis; Sequence Analysis; Public Health; Environment and Public Health

Central Study Contacts

Prof. Dr. med Valérie A McLIn, MD

CONTACT

+41223724545; valerie.mclin@hug.ch

Dr. phil. nat Isabelle Schepens, PhD

CONTACT

+41223724545; isabelle.schepens@hug.ch

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. Med.

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 2, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

CH (1)