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

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

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.

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