Health effects of COL4A1 and COL4A2 gene mutations across the brain, eyes, heart, kidneys, and muscles.

Study of the Familial Phenotype Associated With Mutations in the COL4A1 and COL4A2 Genes

This project will test whether systematic clinical exams and blood tests can reveal early or hidden organ problems in people with COL4A1/COL4A2 mutations and their first-degree relatives.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sex: All
• Sponsor: Meyer Children's Hospital IRCCS (Academic / other)
• Locations: 1 site (Florence, FI)
• Trial ID: NCT07374913 on ClinicalTrials.gov

What this trial studies

This prospective observational cohort enrolls individuals with pathogenic or likely pathogenic COL4A1 or COL4A2 variants and their first-degree family members to map the clinical spectrum across multiple organs. Participants complete a structured questionnaire and carrier or suspected-carrier adults are offered non-invasive ophthalmological and cardiological screening within routine clinical care. Adult non-carrier relatives serve as controls for selected laboratory analyses, and blood samples are collected for plasma biomarker studies including matrix metalloprotein activity. The combined clinical, imaging, and laboratory data aim to clarify variable expressivity and underlying biological mechanisms of COL4A1/COL4A2-related disease.

Who should consider this trial

Good fit: Ideal candidates are individuals of any age with a confirmed pathogenic or likely pathogenic COL4A1 or COL4A2 mutation and their adult first-degree relatives, whether carriers, suspected carriers, or non-carrier controls willing to provide blood samples.

Not a fit: People without COL4A1/COL4A2 mutations or those unable or unwilling to undergo the non-invasive exams or provide informed consent are unlikely to receive direct benefit from participation.

Why it matters

Potential benefit: If successful, the project could enable earlier detection of organ involvement and better guidance for monitoring and managing people with COL4A1/COL4A2 mutations.

How similar studies have performed: Previous case series and genetic reports have documented multi-organ features in COL4A1/COL4A2 carriers, but prospective family-based diagnostic screening combined with biomarker analysis is relatively limited and partly novel.

Eligibility criteria

Inclusion Criteria:

* Individuals (pediatric or adult) with a pathogenic or likely pathogenic mutation in the COL4A1 or COL4A2 genes and a clinical phenotype consistent with small vessel disease.
* Adult first-degree family members (parents, siblings, or children) who are confirmed carriers or suspected carriers of the same COL4A1/COL4A2 mutation.
* Adult first-degree family members who are non-carriers of the pathogenic mutation and who agree to provide a blood sample to be used as controls for laboratory analyses.
* Ability to provide written informed consent; for minors, consent provided by a parent or legal guardian.

Exclusion Criteria:

* Refusal or inability to provide informed consent.
* Individuals who do not meet the inclusion criteria above.
* Any condition that, in the opinion of the investigators, would preclude participation in study procedures or reliable data collection.

Where this trial is running

Florence, FI

• Meyer Children's Hospital IRCSS — Florence, Fi, Italy (Recruiting)

Study contacts

• Study coordinator: SIMONA Balestrini, Md, PhD

Conditions COL4A1\2; COL4A1-Related Brain Small Vessel Disease With Haemorrhage