Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms (ORPHADIAG)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Familial Thoracic Aortic Aneurysm and Aortic Dissection
• Intervention / Treatment: Diagnostic test: Linkage Analysis

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.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

Study Locations

• Italy
  • Milan
    • San Donato Milanese, Milan, Italy, 20097
      • Cardiovascular Genetic Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Families of patients with FTAAD in follow-up in an italian reference centre for genetic aorthopathies.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FTAAD; members of families with FTAAD	Diagnostic test: Linkage Analysis; WES-Linkage analysis in families with FTAAD in follow-up in an Italian reference centre for genetic aorthopathies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA sequences in FTAAD	Identify those chromosome regions containing the DNA sequences responsible for each enrolled member of FTAAD families	16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutations associated with Mendelian and monogenic diseases	Identification of potential sites for the location of the responsible gene and mutations associated with Mendelian and monogenic diseases.	24 months

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato
• Collaborators: IRCCS Ospedale San Raffaele

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2024
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; Linkage analysis; familial thoracic aortic aneurysm and dissection
• Additional Relevant MeSH Terms: Dissection, Blood Vessel; Acute Aortic Syndrome; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Dissection; Aortic Aneurysm, Thoracic
• Other Study ID Numbers: ORPHADIAG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be considered for sharing after data collection and analysis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No