IntraCranial ANeurysms: From Familial Forms to Pathophysiological Mechanisms
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Nantes University Hospital
- Enrollment
- 3,078
- Locations
- 20
- Primary Endpoint
- Presence or absence of genetic abnormalitie
Study Overview
Brief Summary
Intracranial aneurysm (IA) is an asymptomatic cerebrovascular abnormality affecting 3.2% of the general population. The devastating complication of IA is its rupture, resulting in subarachnoid haemorrhage that can lead to severe disability and death. Unfortunately, there are neither reliable clues nor diagnostic tools to predict the formation and/or the fate of an IA in a given individual. Also, there is no pharmacological drug available to prevent the rupture of aneurysm and subsequent subarachnoid haemorrhage. Current treatments are invasive with a significant risk of procedural morbidity. Thus, still now, the management of patients with IA remains extremely challenging and still controversial. Although the pathogenesis of IA has been the subject of many studies for the last decade, the mechanisms underlying IA formation, growth and rupture are still mostly unknown and relevant animal models of IA are not available. Familial history of IA predisposes to IA formation and rupture and increasing evidence suggest a genetic component of IA formation, with heterogeneous modes of inheritance and penetrance. This project, gathering neuroradiologists, geneticists and vascular biologists, addresses the urgent need to understand the pathogenic mechanisms of IA to develop diagnostic and predictive tools of risk of IA. The investigators propose to identify IA-causing variants by whole-exome sequencing in familial forms of the disease. The investigators hypothesises that the functional analysis of the causal/susceptibility variants thus identified will provide clues to understanding the pathological mechanisms of IA formation, and the bases for developing diagnostic tools. This project aims at meeting this challenge. Based on preliminary data that already allowed to identify such a variant, and the combination of genetic and functional investigations, the specific objectives of this project are: - To identify IA-causing variants in familial forms of the disease by whole-exome sequencing; - To understand the function of these genes/variants in the formation and rupture of IA by molecular and cellular approaches and generation of relevant animal models; - To discover potential biomarkers of risk of IA formation and/or rupture.
Study Design
- Study Type
- Observational
- Observational Model
- Family Based
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients who have shown the inability or refusal to sign the consent informed biocollection
- •syndromic diagnosis known as AIC provider
- •Marfan Syndrome
- •AOS with SMAD 3
- •Danlos Syndrome Elhers type II and IV
- •Autosomal Dominant Polycystic
- •Moyamoya Syndrome
- •character of IA:
- •Dissecting or fusiform
- •Combined with an arteriovenous malformation
- •Blister-like
- •Pathology of the cerebral white matter detected on MRI suggestive:
- •Mutation COL4A1
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Presence or absence of genetic abnormalitie
Time Frame: Until one year
Identification of genetic abnormalities segregant with the presence of intracranial aneurysms in the informative families recruited. Sequencing of the whole exome in a cohort of patients carriers of familial forms of intracranial aneurysms. Analysis of blood level of the GAIA 1 protein in a large cohort of familial and sporadic carriers of intracranial aneurysms
Secondary Outcomes
No secondary outcomes reported