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

NCT05867979 | Recruiting

• 2 other identifiers: RECHMPL22_02362022-A02498-35
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Disorder of Sex Development, 46,XY

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of Participants with mosaic structural variants detected by OGM

  Day of inclusion

Study Arms (1)

patients with DSD and inconclusive molecular diagnosis

EXPERIMENTAL

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

Interventions

Identify structural variants by Optical Genome Mapping of DNA extracted from blood leukocytes DIAGNOSTIC_TEST

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.

patients with DSD and inconclusive molecular diagnosis

Eligibility Criteria

• Age: 6 Months+
• Gender Eligibility Details: XY male karyotype (i.e. on all leukocytes studied).
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

University Hospital Montpellier

Montpellier, 34000, France

RECRUITING

MeSH Terms

Conditions

Disorder of Sex Development, 46,XY

Condition Hierarchy (Ancestors)

Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Françoise PARIS, MD PhD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Françoise PARIS, MD PhD

CONTACT

+33615106371; f-paris@chu-montpellier.fr

Anne BERGOUGNOUX, PharmD PhD

CONTACT

+33411759879; anne.bergougnoux@inserm.fr

Study Design

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

Model Details: This is a single-center molecular biology pilot study on a single group of 20 patients with a disorder of sex development and inconclusive molecular diagnosis. The 20 blood samples from patients with severe or moderate DSD, with an inconclusive diagnosis will benefit from the Optical Genome Mapping.

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 22, 2023
• Study Start: February 5, 2024
• Primary Completion: February 15, 2026
• Study Completion: February 15, 2026
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)