Clinical trial NCT05146375: Genes Modulating the Severity of Aortic Aneurysms (MSF1-TGFBR2)
Official title: Genes Modulating the Severity of Aortic Aneurysms (MSF1-TGFBR2)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Thoracic Aortic Aneurysm
Keywords: Vascular Diseases, Aneurysm
TGFBR2 mutation
Lead sponsor: French Cardiology Society
Sponsor class: OTHER
Collaborators: name: Fédération Française de Cardiologie
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2021-12-06
Enrollment: 17
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 53 members of the MFS1 family are currently identified and have a medical follow-up in the national referral center for Marfan syndrome of the hospital Bichat-Claude Bernard, Paris.

Brief summary: This project concerns a population at risk of sudden death by dissection of the thoracic aorta. Its interest is to make it possible to recognize the genes that protect or worsen the evolution of aneurysms, to better understand the mechanisms involved, to detect and treat aneurysms of the thoracic aorta, wich is a pathology that is completely silent clinically until life-threatening complications.

The variability in the severity of the disease within the same family is related to modifier genes.

The objective is to find the modifying factors that account for the variability in the severity of the progression of aneurysms of the thoracic aorta.

Detailed description: Thoracic aortic aneurysms are silent, asymptomatic, potentially fatal pathologies due to the risk of aortic dissection. More and more often they are found during imaging tests done for another reason. Some aneurysms have genetic origin (autosomal dominantly inherited) and are particularly interesting because they can be recognized early (due to possible family screening), which allows us to understand the natural history of this pathology. The discovery of genes whose mutations explain the occurrence of these family aneurysms (initiator gene) has also made it possible to improve family screening and to better understand the pathophysiology of these aneurysms: we now recognize 3 groups of genes involved (extracellular matrix, contractile proteins of smooth muscle cell, TGF-β pathway (Transforming Growth Factor) \[including mutations in TGF-β receptor 2 gene, TGFBR2\]).

The variability in the severity of signs and aortic involvement is particularly marked in patients with aortic aneurysms due to mutations in the TGFBR2 gene. Some patients with these mutations present aggressive aneurysms with early dissection. Other patients have isolated late-onset aneurysms, and others have no signs.

This variability generates problems for clinical practice to give appropriate genetic advice, but also to adapt imaging monitoring, therapy, or sports restriction.

The present protocol aims is to investigate the variability in the severity of the disease within a large family carrying a mutation in the TGFBR2 gene. The MFS1 family is a family in which the aortic pathology is due to a mutation in the TGFBR2 gene. All patients with this family carry the same TGFBR2 mutation, heterozygous.

Eligibility criteria: Inclusion Criteria:

Member of MSF1 family. The MFS1 family is a family in which the aortic pathology is due to a mutation in the TGFBR2 gene. All patients with this family carry the same TGFBR2 mutation (heterozygous)

Exclusion Criteria:

Refusal or linguistic or psychological inability to sign informed consent

Primary outcomes:
measure: Clinical phenotype
timeFrame: day 1
Secondary outcomes:
measure: TGFBR2 and other gene mutations involved in aneurysms
timeFrame: All samples will be analysed at the same time, at the end of the recruitment.
measure: Genotype analysis
timeFrame: All samples will be analysed at the same time, at the end of the recruitment.
measure: Transcriptome analysis
timeFrame: All samples will be analysed at the same time, at the end of the recruitment.
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Bichat-Claude Bernard
Study officials:
affiliation: Hopital Bichat-Claude Bernard
name: Guillaume JONDEAU, MD
role: PRINCIPAL_INVESTIGATOR
References: