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

Not Applicable

• Conditions: Genetic Disorders in Pregnancy
• Interventions: Diagnostic Test: NIPT Test

• Registration Number: NCT03688594
• Lead Sponsor: University Hospital, Strasbourg, France

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-22
• Status Verified: 2018-09
• Study First Submitted: 2018-09-26
• Study First Submitted QC: 2018-09-26
• Last Update Submitted: 2018-09-26
• Study First Posted: 2018-09-28
• Last Update Posted: 2018-09-28
• Primary Completion: 2019-05-22
• Study Completion: 2019-05-23

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
couple : man and pregnant women	NIPT Test	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)

Trial Locations

Locations (1)

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France