Clinical trial NCT06783803: Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms
Official title: Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Familial Thoracic Aortic Aneurysm and Aortic Dissection
Keywords: familial thoracic aortic aneurysm and dissection
Linkage analysis
biomarkers
Lead sponsor: IRCCS Policlinico S. Donato
Sponsor class: OTHER
Collaborators: name: IRCCS Ospedale San Raffaele
First posted: 2025-01-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Families of patients with FTAAD in follow-up in an italian reference centre for genetic aorthopathies.

Brief summary: The aim of this study is to describe the effectiveness of the application of Linkage Analysis, compared to the standard procedures currently provided by the italian NHS, in the identification of thoracic aortic aneurysms and dissection (TAAD) transmission markers in individuals with familial TAAD.

Detailed description: According to current guidelines, it is important to screen first-degree relatives of patients with familial thoracic aortic aneurysm and dissection (FTAAD) using imaging techniques in order to detect any undiagnosed or asymptomatic cases. The current diagnostic methods for FTAAD involve clinical and instrumental diagnosis. In addition to these methods, genetic analysis through DNA testing, using a blood sample has become an essential tool. The use of massive parallel sequencing (NGS) of multiple genes or the entire exome (Whole Exome Sequencing - WES) is considered the gold standard for genetic diagnosis of FTAAD. However, it should be noted that linkage studies are not currently included in the diagnostic protocols of the Italian National Health System, although they may be helpful in complex familial cases where DNA sequencing has not provided conclusive evidence.

Eligibility criteria: Inclusion Criteria:

* Patients with ascending thoracic aortic aneurysms in the absence of a mutation identified by WES
* Subjects with small and medium artery aneurysms in the absence of a mutation identified by WES
* Relatives of individuals with ascending thoracic aortic aneurysms in the absence of a mutation identified by WES
* Relatives of individuals with ascending thoracic aortic aneurysms in the absence of a mutation identified by WES
* Signed informed consent

Exclusion Criteria:

* Subjects wit syndromic FTAAD with WES identified gene mutation
* Subjects wit non-syndromic FTAAD with WES identified gene mutation

Primary outcomes:
measure: DNA sequences in FTAAD
timeFrame: 16 months
Secondary outcomes:
measure: Mutations associated with Mendelian and monogenic diseases
timeFrame: 24 months
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: Cardiovascular Genetic Centre
state: Milan
Study officials:
References:
citation: Isselbacher EM, Lino Cardenas CL, Lindsay ME. Hereditary Influence in Thoracic Aortic Aneurysm and Dissection. Circulation. 2016 Jun 14;133(24):2516-28. doi: 10.1161/CIRCULATIONAHA.116.009762.
citation: Carino D, Agostinelli A, Molardi A, Benassi F, Gherli T, Nicolini F. The role of genetic testing in the prevention of acute aortic dissection. Eur J Prev Cardiol. 2018 Jun;25(1_suppl):15-23. doi: 10.1177/2047487318756433.