Identification of Y Chromosome From Free Circulating DNA in Patients With Turner Syndrome

Not Applicable

Recruiting

• Conditions: Turner Syndrome
• Interventions: Genetic: cfDNA analysis

• Registration Number: NCT06202846
• Lead Sponsor: University Hospital, Strasbourg, France

Brief Summary

Turner syndrome affects 1/2500 female newborns. It is characterized by a short stature, gonadal dysgenesis and bone anomalies. It is secondary to X chromosome abnormality. The clinical course can be marked by various complications, including degeneration of gonadal streaks into cancer (gonadoblastoma). The risk of gonadoblastoma is increased by the presence of Y chromosome, with a risk of 19 to 43%. However, Y chromosome material may be difficult to identify due to its mosaic state, at varying rates depending on the tissue. Free circulating DNA (cfDNA) corresponds to fragments of extracellular DNA present in the plasma, released into the circulation during cell death processes by the various tissues of the body. Due to its multiple tissue origins and easy collection, cfDNA appears to be a suitable matrix for searching for low mosaic Y chromosome sequences in patients with Turner syndrome.

The main objective of the study is to develop a cfDNA-based test to look for Y chromosome sequences in 50 patients with Turner syndrome. The secondary objectives are to determine the mosaic detection threshold of this test and to compare the performance of this test with the fluorescence in situ hybridization (FISH) technique used in routine diagnosis.

This study will assess the detection sensitivity of this test and its relevance in a clinical context.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-20
• Study First Submitted QC: 2024-01-09
• Study First Posted: 2024-01-12
• Study Start: 2024-02-28
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06
• Primary Completion: 2028-06
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 50

Inclusion Criteria

• patient aged 2 to 74 years
• with a diagnosis of Turner syndrome confirmed by karyotype
• who have given their consent or whose legal representative(s) have given their consent(s) consent(s) to participate in the study
• affiliated to the French Social Security system or benefiting from such a system

Exclusion Criteria

• male phenotype
• patient or legal representative(s) with comprehension difficulties (linguistic, etc.)
• patients covered by articles L.1121-5 to L.1121-8 of the CSP (French Public Health Code)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Turner syndrome patients	cfDNA analysis	Patients with a Turner syndrome confirmed by karyotype.

Primary Outcome Measures

Name	Time	Method
Proportion of patients presenting Y chromosome material detected by the cfDNA test	From date of inclusion to date of genetic analysis result	An inferential analysis will allow to estimate the proportion of Y chromosome detection by the cfDNA test and secondly to compare it with data from the literature.

Secondary Outcome Measures

Name	Time	Method
Y chromosome mosaic rate detectable by the cfDNA test.	Up to 26 months	Dilution of female (XX) and male (XY) plasma in order to evaluate the detection limit of y chromosome material by the cfDNA test.
Comparison between the cfDNA test and routine FISH analysis	Up to 30 months	An inferential analysis will compare the proportion of Y chromosome detection by the cfDNA test and by FISH.

Trial Locations

Locations (2)

Hospice Civil de Lyon; 🇫🇷 Lyon, France

Hopitaux Universitaire de strasbourg; 🇫🇷 Strasbourg, France