Reinterpretation of CNV With Unknown Significance: a 5-year Retrospective Analysis

NCT04575350 | Completed

• 1 other identifier: ReAC
• Study Type: observational
• Target: 282
• Locations: 1 country
• Sites: 1

Brief Summary

We aim to assess the usefulness of systematic reinterpretation of CNV of unknown significance. To investigate this question we will study all CNV of unknown significance detected between 2010 and 2017.

Conditions

Genetic Disease; CNV; Genetic Counseling; Array CGH

Outcome Measures

Primary Outcomes (1)

• Define the overall rate and per year of reclassification of CNVs after systematic analysis of all those identified as VUS between 2010 and 2016.

  The proportion of pathogenic variants will correspond to the percentage of pathogenic variants among all reclassified variants.

  between july 2019 and november 2019

Secondary Outcomes (5)

• Among the reclassified CNVs, define the proportion of pathogenic variants ;

  between july 2019 and november 2019

• Among the CNVs reclassified as pathogens, define the proportion of new diagnoses ;

  between july 2019 and november 2019

• Compare the rate of reclassification of CNVs by type (deletion/duplication)

  between july 2019 and november 2019

• Compare the size of the CNV according to the type of reclassification of the variant.

  between july 2019 and november 2019

• Compare the reclassification rate by type of disease.

  between july 2019 and november 2019

Study Arms (1)

Cohort

no intervention.

Genetic: reinterpretation of CNV

Interventions

reinterpretation of CNV GENETIC

Reinterpretation of CNV of unknown significance

Cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

General population

You may qualify if:

• Signed consent for array-CGH (authorization for the conservation of a biological sample and its subsequent use to continue investigations);
• array-CGHcarried out at the genetics laboratory in Nancy between 1st January 2010 and 31th December 2017 (considering the date of validation of the report);
• Identification of variations of unknown clinical significance.

You may not qualify if:

• none

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

Lorraine University

Nancy, France

Location

Related Publications (2)

• Palmer E, Speirs H, Taylor PJ, Mullan G, Turner G, Einfeld S, Tonge B, Mowat D. Changing interpretation of chromosomal microarray over time in a community cohort with intellectual disability. Am J Med Genet A. 2014 Feb;164A(2):377-85. doi: 10.1002/ajmg.a.36279. Epub 2013 Dec 5.

  PMID: 24311194 BACKGROUND

• Ravel JM, Renaud M, Muller J, Becker A, Renard E, Remen T, Lefort G, Dexheimer M, Jonveaux P, Leheup B, Bonnet C, Lambert L. Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study. Genome Med. 2023 May 23;15(1):39. doi: 10.1186/s13073-023-01191-6.

  PMID: 37221613 DERIVED

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Lambert Laëtitia, MD, PhD

  CHRU Nancy, Lorraine University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 5, 2020
• Study Start: January 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: October 5, 2020

Record last verified: 2020-09

Locations

FR (1)