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

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.

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.

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)