Non Invasive Prenatal Test of Rare Genetic Diseases: Application to Rare Intellectual Disabilities

Study Overview
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Brief Summary
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The aim of this study is to evaluate performances of a NIPT test based onto the study of the maternal blood to search known genetic mutations already detected in the family and potentially inherited by the fetus. This test will avoid an invasive prenatal diagnosis in those families with a known genetic risk. The performance of this test will be evaluated in terms of sensitivity and specificity with an adapted statistic model. Secondary objectives of the protocol are To adapt NIPT to small DNA quantity (5-50 ng) To adapt bioinformatics pipeline to low rate of mosaicism To develop a tool to quantify the fetal fraction To evaluate the robustness of the method This test is based onto capture and high throw put sequencing adapted to cell free plasmatic DNA of pregnant women in order to detect point mutation present in her fetus. This approach has been previously described for others clinical applications such as liquid biopsy in cancers but not for NIPT analysis.

Official Title
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Non Invasive Prenatal Test of Rare Genetic Diseases: Application to Rare Intellectual Disabilities

Conditions
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Genetic Disorders in Pregnancy

Intervention / Treatment
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* Diagnostic Test: NIPT Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Couple (father, mother) > 18 ans Pregnant woman (> 12-15 weeks of gestation) with a fetal sampling needed in standard care. informed consent obtained couple affiliated to the social insurance in France Exclusion Criteria: DNA extraction failure Absence of informed consent Father or mother placed under judicial protection or under guardianship or tutorship

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: couple : man and pregnant women<br> | Diagnostic Test: NIPT Test<br>* This test is based onto capture and high throw put sequencing adapted to cell free plasmatic DNA of pregnant women in order to detect point mutation present in her fetus. This approach has been previously described for others clinical applications such as liquid biopsy in cancers but not for NIPT analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection yield of fetal paternally transmitted single nucleotid variations (SNV) in free cell maternal DNA Absence of non fetal paternally transmitted single nucleotid variations (SNV) in maternal free cell DNA (cfDNA) |  | Measurement will be performed at the end of the protocol (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of SNV detection efficiency of several bioinformatics pipeline Robustness evaluation in function of - Fetal percent in cfDNA - Genomic region - Initial input of cfDNA |  | Measurement will be performed at the end of the protocol (12 months) |