Biocollection on the Familial Forms of Intracranial Aneurysm
- Conditions
- Intracranial Aneurysm
- Registration Number
- NCT02848495
- Lead Sponsor
- Nantes University Hospital
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 411
- Patients who have shown the inability or have refused to sign the consent informed biocollection
- Syndromic diagnosis known as IA 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
- Mycotic
- Pathology of the cerebral white matter detected on MRI, evoking:
- COL4A1 mutation
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method DNA analysis to identify new genes (and new physiological pathways) associated to the risk of intracranial aneurysm Until one year
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (8)
AP-HP, Henri Mondor hospital
🇫🇷Créteil, France
CHD La Roche sur YON
🇫🇷La Roche sur YON, France
Nantes University Hospital
🇫🇷Nantes, France
Tours University Hospital
🇫🇷Tours, France
Rouen University Hospital
🇫🇷Rouen, France
University Hospital Poitiers
🇫🇷Poitiers, France
University Hospital Rennes
🇫🇷Rennes, France
Bordeaux University Hospital
🇫🇷Talence, France