Prenatal Screening for Imprinting Anomalies Implicated in Beckwith Wiedemann and Silver Russell Syndromes

Study Overview
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Brief Summary
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Losses of imprinting are involved in various syndromes. Those occurring in the 11p15 region lead to Beckwith-Wiedemann and Silver-Russell Syndromes. These losses of imprinting follow a mosaic pattern, rendering their detection difficult, especially given the scarcity of available DNA in amniotic fluid. Thus, in spite of growing demand, prenatal diagnosis (PND) for imprinting abnormalities of the 11p15 region is not available. The recent development of a quantitative PCR method that permits the methylation index (MI) of imprinted regions to be calculated renders PND technically possible. Nevertheless, because of the mosaic nature of these anomalies, it is essential to verify that the methylation pattern of the 11p15 region obtained from the amniotic fluid matches that obtained from the blood.

Detailed Description
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To evaluate the agreement between the methylation index of the 11p15 region obtained using DNA extracted from amniocytes and that extracted from cord blood leukocytes, by calculating the intraclass correlation coefficient (ICC). Ancillary study : This second part of the study aims to determine the standard of methylation index of the 11p15 region (inclusion of 100 additional patients). The use of amniotic liquid will allow to calculate : the average of methylation index, the value of the standard deviation the inter-assay coefficient of variation for the test-used.

Official Title
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Prenatal Screening for Imprinting Anomalies Implicated in Beckwith Wiedemann and Silver Russell Syndromes

Conditions
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Pregnant Women Requiring Amniocentesis

Intervention / Treatment
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* Genetic: Methylation Index


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women, 18 years of age or older Requiring amniotic fluid sampling in the context of pregnancy care after 15 weeks of amenorrhea Having provided written informed consent Followed at Trousseau Hospital or Clinique des Bluets during their pregnancy Covered by or beneficiary of a state health insurance program (except for medical aid programs) Exclusion Criteria: Warning signs on ultrasound that require a medical termination of pregnancy to be discussed even before amniocentesis is performed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregnant women requiring amniocentesis<br>Pregnant women requiring amniocentesis | Genetic: Methylation Index<br>* To calculate the methylation index (MI) of imprinted regions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methylation Index (MI) of the 11p15 region using DNA extracted | To evaluate the agreement between the MI of the 11p15 region obtained using DNA extracted from amniocytes and that extracted from cord blood leukocytes, by calculating the intraclass correlation coefficient (ICC). | 27 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MI using the placenta | To calculate the MI using the placentas of the same individuals and to evaluate its agreement with the MIs obtained above. | 27 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MI, amniocentesis, cord blood, placenta, Silver Russell Syndrome, Beckwith Wiedemann Syndrome