Genomic Profiling of Genetic and Rare Diseases

NCT06926127 | Recruiting

• 1 other identifier: 6987
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

In Italy, over 2 million patients are affected by Rare Diseases (RD), which pose significant challenges due to their clinical diversity, long diagnostic processes (often 4-5 years), and high socio-healthcare costs. The Italian healthcare system has recognized these challenges, leading to initiatives like a national Rare Diseases (RD) registry, a comprehensive list of Rare Diseases (RDs) eligible for healthcare exemptions, and the establishment of a National Committee for Rare Diseases. Research on the genetic mechanisms of Rare Diseases (RDs) is robust, particularly for innovative therapies, and ranks second to oncology. The Policlinico Universitario A. Gemelli IRCCS Foundation serves as a key reference institute for Rare Diseases (RD) in Lazio, managing over 10,000 patients through accredited centers. A recent initiative aims to enhance the Rare Diseases network by integrating genomic knowledge with clinical practice. The project focuses on utilizing Next Generation Sequencing (NGS) for early genetic diagnosis, promoting personalized medicine. Given the challenges the National Health Service faces in resource allocation for Rare Diseases (RD) and the recent approval of a new outpatient healthcare tariff, this initiative is timely. The foundation seeks to replace targeted genetic tests with Whole Exome Sequencing (WES), increasing the identification of molecular conditions and reducing diagnostic turnaround times.

Conditions

Rare Diseases; Genetic Disease

Outcome Measures

Primary Outcomes (1)

• Reduce diagnostic timelapse of rare genetic conditions

  To reduce the time frame between first clinical evaluation to molecular diagnosis by improve the genomic characterization of rare genetic conditions trought implementation of the actual molecular analysis (from targeted panels to whole exome sequencing - WES

  from 1 year to 4 years

Secondary Outcomes (3)

• Improve the hospital's diagnostic rate

  5 years

• Identify an increasing number of molecular variants

  5 years

• Reduce healthcare costs for a definitive diagnosis

  5 years

Study Arms (1)

Patients

EXPERIMENTAL

Patients with suspected rare or specific genetic diseases diagnosed based on clinical presentation and instrumental examination performed by geneticist or by a specialist physician experienced in the specific condition (e.g., phenotype associated with a known genetic syndrome, known neuromuscular disease, or known specific regional disease such as hypertrophic/dilated cardiomyopathy) are enrolled to undergo genetic testing for diagnostic purposes and to improve personalized treatment.

Genetic: Whole Exome Sequencing (WES)

Interventions

Whole Exome Sequencing (WES) GENETIC

Blood samples, buccal swabs, and pathological tissue samples (skin/muscle) will be collected, and subsequently, DNA extracted from those tissues will be used for genomic analysis using Whole Exome Sequencing. The sample will follow the diagnostic pipeline already established inside the hospital. Moreover, the remaning aliquots of DNA extracted from the tissue (peripheral blood or tissue specimen) will be sent by the Genomics core facility to the Biobank for storage upon analysis completion.

Patients

Eligibility Criteria

• Age: 1 Minute - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 0-90 years
• Patients with suspected rare disease/genetic disease diagnosed based on the clinical criteria/instrumental examination performed by a reference physician experienced in the specific condition (e.g., phenotype attributable to a known genetic syndrome, known neuromuscular disease, known organ-specific disease such as hypertrophic/dilated cardiomyopathy) to undergo genetic analysis
• Patients with a phenotype suggestive of a rare disease/genetic disease not specifically linked to a known condition
• Patients with suspected rare disease/genetic disease, who have undergone quantitative genetic analyses (e.g., array-CGH) or qualitative analyses (e.g., NGS panel of known genes), which yielded negative results
• Patients who have already received a genetic etiological diagnosis and for whom the current project can address further questions such as the personalization of a prevention or therapy pathway.

You may not qualify if:

• Individuals (patients, parents, and/or legal guardians) who refuse to participate in the project for any reason.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC PEDIATRIA

Rome, Lazio, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Rare Diseases; Genetic Diseases, Inborn

Interventions

Exome Sequencing

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Giovanni Scambia

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giovanni Scambia

CONTACT

+390630155701; giovanni.scambia@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: April 13, 2025
• Study Start: November 5, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): February 28, 2030
• Last Updated: April 13, 2025

Record last verified: 2024-10

Locations

IT (1)