Prospective Study to Assess Medical Performance of Optical Mapping and Long Read Sequencing in Detecting Numerical and Structural Chromosome Abnormalities

NCT05290051 | Recruiting

• 1 other identifier: C21-35
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Chromosomal aberrations are major causes of developmental disorders (Intellectual disability (ID), multiple congenital anomalies (MCA), autism spectrum disorders (ASD)) as well as reproductive disorders (RD) in particular gametogenesis defects and recurrent miscarriages. Current first tier genetic investigations for chromosome analysis in clinical settings include karyotyping in case of RD (5 \~ 10% diagnosis rate) and chromosomal microarrays (CMA) in case of ID/MM (10 \~ 20% diagnosis rate). However, both assays show significant drawbacks, e.g. low resolution for karyotyping and inability to detect balanced structural rearrangement for CMA. Optical genome mapping and long read genome sequencing are emerging technologies that offer new opportunities to overcome these limitations and allow for a higher resolution chromosome analysis. This project aims at assessing the performance of optical mapping and long read whole genome sequencing compared to current gold standard cytogenetics methods in a prospective study. The investigator will evaluate their ability to become the all-in-one methodology for genomic analysis that could replace both karyotype and CMA and their added-value compared to these latter by uncovering new diagnoses.

Conditions

Infertility; Intellectual Disability; Malformation; Miscarriage

Outcome Measures

Primary Outcomes (1)

• Percentage of verified clinically significant chromosomal aberrations detected by Bionano® and Nanopore® compared to the percentage of those detected by karyotyping or CMA according to reason for referral.

  The significance of an aberration is assessed according to international guidelines, clinical history, as well as publications and public databases.

  Through study completion, an average of 1 year

Secondary Outcomes (4)

• Incidence and distribution of different kinds of chromosomal aberrations per category of referral.

  Through study completion, an average of 1 year

• Type of chromosome abnormalities that are overlooked by Bionano® and/or Nanopore® while detected by standard-of-care techniques

  Through study completion, an average of 1 year

• Percentage of patients for which the detection of a chromosomal aberration by Bionano® or Nanopore® and not by karyotyping or CMA resulted in a change in the disease management

  Through study completion, an average of 1 year

• Overall cost and benefit of each technique including delay to diagnosis and changes in the disease management

  Through study completion, an average of 1 year

Study Arms (1)

Patients referred for cytogenetic analysis

EXPERIMENTAL

Analysis of patient DNA with Optical Genome Mapping (Bionano®) and long read Sequencing (Nanopore®) in search for chromosome abnormalities (aneuploidies and SV)

Genetic: Optical Genome Mapping (Bionano®); Genetic: Longread sequencing (Nanopore®)

Interventions

Optical Genome Mapping (Bionano®) GENETIC

Search for chromosome abnormalities through alteration of the optical map of the genome compared to reference genome using the Bionano® 's pipeline.

Patients referred for cytogenetic analysis

Longread sequencing (Nanopore®) GENETIC

Search for chromosome abnormalities from the sequencing data obtain from high molecular weight DNA molecules using dedicated analysis pipeline.

Patients referred for cytogenetic analysis

Eligibility Criteria

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

You may not qualify if:

• ID in a context of perinatal suffering (e.g. hypoxia during labor)
• Children born to non-native French-speaking parents in case of speech/language retardation
• Obstructive azoospermia
• Children under 5kg or whenever blood sampling cannot meet the required volume.
• Missing or wrong blood collection tube
• Insufficient blood volume
• Missing or incomplete consent to research (e.g. only one parental consent for a child)

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• CHU Rennes - Hopital Pontchaillou: collaborator
• APHP: collaborator
• CHU de Rouen - Accueil: collaborator
• University Hospital, Strasbourg: collaborator
• Université Montpellier: collaborator
• University Hospital, Clermont-Ferrand: collaborator
• CHU de Reims: collaborator
• APHM: collaborator
• Hospices Civils de Lyon: collaborator

Study Sites (1)

Cochin APHP

Paris, 75014, France

RECRUITING

MeSH Terms

Conditions

Infertility; Intellectual Disability; Congenital Abnormalities; Abortion, Spontaneous

Interventions

Nanopores

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Nanostructures; Manufactured Materials; Technology, Industry, and Agriculture

Central Study Contacts

Dr Laila EL KHATTABI

CONTACT

01 58 41 35 29; Laila.el-khattabi@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Gold standard analyses run as usual with results issued to patients Evaluated analyses run and analyzed blind to care provider and investigator Comparison of results between gold standard and tested analyses at the end of the study
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Comparison of new diagnostic procedures with gold standard used in clinical setting

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: March 22, 2022
• Study Start: September 26, 2022
• Primary Completion: March 26, 2025
• Study Completion (Estimated): June 26, 2026
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

FR (1)