Search for Structural Variants in Patients With DSD and Inconclusive Molecular Diagnosis (GENEXPLOR)

Search for Structural Variants in Patients With Disorders of Sex Development (DSD) and Inconclusive Molecular Diagnosis GENEXPLOR-DSD

The goal of this clinical trial is to identify structural variants by Optical Genome Mapping (OGM) in the described participant population.

The main questions it aims to answer are:

• Identify constitutional structural variants by OGM of DNA extracted from blood leukocytes of patients with DSD for which the molecular diagnosis is inconclusive.
• Identify mosaic structural variants (present in a subpopulation of somatic cells only) by OGM of DNA extracted from blood leukocytes of patients with DSD for which the molecular diagnosis is inconclusive.
• Compare the diagnostic yields of OGM and of Comparative Genome Hybridization Array (CGH array) methods.
• Compare the diagnostic yields of the OGM and of Whole Genome Sequencing (National Sequencing Program), only if performed.

Participants will be required to:

• a follow-up interview with a physician to review their own and family medical and surgical history, with a focusing on DSD.
• An interview to assess their exposure to environmental pollutants during fetal life, using a validated questionnaire.
• a blood test with a 5mL tube to perform optical genome mapping analysis.

Study Overview

• Status: Recruiting
• Conditions: Disorder of Sex Development, 46,XY
• Intervention / Treatment: Diagnostic test: Identify structural variants by Optical Genome Mapping of DNA extracted from blood leukocytes

Detailed Description

Patients with severe or moderate disorder of sex development (DSD) with a inconclusive molecular diagnosis will benefit from optical genome mapping analysis.

A venous blood sample on ethylenediaminetetraacetic acid (EDTA) tube (5mL) will be taken in order to extract the DNA that will be used for the optical genome mapping analysis.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Françoise PARIS, MD PhD; Phone Number: +33615106371; Email: f-paris@chu-montpellier.fr
• Study Contact Backup: Name: Anne BERGOUGNOUX, PharmD PhD; Phone Number: +33411759879; Email: anne.bergougnoux@inserm.fr

Study Locations

• France
  • Montpellier, France, 34000
    • Recruiting
    • University Hospital Montpellier
    • Contact: Anne BERGOUGNOUX, PharmD PhD
    • Sub-Investigator: Nicolas KALFA, MD PhD
    • Sub-Investigator: Jacques PUECHBERTY, MD PhD
    • Sub-Investigator: Vincent GATINOIS, MD
    • Sub-Investigator: Franck PELLESTOR, PUPH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• homogeneous XY male karyotype.
• patient at least 6 months old
• severe to moderate DSD (Prader 1 to 5) for which the molecular diagnosis is inconclusive after a gene panel analysis.

Exclusion Criteria:

• subject with a homogeneous or mosaic XX, or monosomal X karyotype.
• subject with an aneuploidy.
• subject with a conclusive molecular diagnosis explaining the observed DSD (i.e. carrier of a causal genotype already well characterized by functional studies)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients with DSD and inconclusive molecular diagnosis; The one arm of the study will have a venous blood draw as part of the research. 1 EDTA tube of 5mL will be collected.	Diagnostic test: Identify structural variants by Optical Genome Mapping of DNA extracted from blood leukocytes; The one arm of the study will have a venous blood draw as part of the research. 1 EDTA tube of 5mL will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with a constitutional structural variants detected by OGM	A structural variant, present at the constitutional state in leukocyte DNA, and considered as likely pathogenic or pathogenic, identified by OGM in at least one of the included patients.	Day of inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with mosaic structural variants detected by OGM	A structural variant, present at the mosaic state in leukocyte DNA (i.e. allelic imbalance less than 0.40), and considered as likely pathogenic or pathogenic, identified by OGM in at least one of the included patients.	Day of inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Françoise PARIS, MD PhD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2024
• Primary Completion (Estimated): June 15, 2025
• Study Completion (Estimated): June 15, 2025

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 11, 2023
• First Posted (Actual): May 22, 2023

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Urogenital Abnormalities; Congenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disorders of Sex Development; Disorder of Sex Development, 46,XY
• Other Study ID Numbers: RECHMPL 22_0236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No