Realization of Sequencing of All Known Human Genes in Case of Detection of Cerebral, Renal or Ophthalmological Fetal Malformations During Pregnancy in Order to Make an Etiological Diagnosis and to Precise the Fetal Prognosis
PRENATEX
Contribution of the Exome Sequencing in Antenatal Period Behind Ultrasound Features Suggestive of a Rare Genetic Disease
1 other identifier
interventional
90
1 country
12
Brief Summary
Congenital malformations concern 3% of pregnancies; most of them can be seen during pregnancy. For some malformations, an invasive sample (trophoblast biopsy or amniocentesis) is proposed to search a chromosomal abnormality by the technique of DNA chip. However, some strongly suggestive signs of a genetic (and not chromosomal) pathology have a very low diagnostic rate with this technique. In the absence of an etiological diagnosis, the prognosis for the unborn child is very difficult to assess, as we can't know if the fetal malformation is really isolated or associted to other unseen features as part of a syndromic condition. For some malformations strongly suggestive of a genetic condition, we propose to realize an exome (i.e. all coding parts of the genome) sequencing of the trio (child and the 2 parents) with a delivery time compatible with the emergency situation of a pregnancy (6 weeks maximum). We will apply bioinformatics filters to analyse only genes known to be involved in the malformation present in the unborn child and thus avoid the identification of variants in unrelated genes. These lists of genes have been previously validated by the Rare Disease Health Sectors and the affiliated diagnostic laboratories. The selected malformations are: 1) anomalies of the central nervous system (microcephaly (\<- 2DS) with anomalies of gyration, anomalies of the posterior fossa, anomalies of the midline except agenesis of the corpus callosum), 2) ophthalmological anomalies (microphthalmia, hyperplasia vitreous) and 3) renal abnormalities (large hyperechoic kidneys).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Aug 2020
Typical duration for not_applicable
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2020
CompletedFirst Posted
Study publicly available on registry
May 28, 2020
CompletedStudy Start
First participant enrolled
August 5, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2023
CompletedNovember 13, 2020
November 1, 2020
1.1 years
May 26, 2020
November 10, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Diagnostic contribution of the exome sequencing in antenatal period in comparison with the chromosomal analysis (CGH-array) realized in current health care
Comparison of the number of genetic diagnoses made by exome sequencing and by CGH-array.
13 months
Secondary Outcomes (2)
Effects on pregnancy management and/or postnatal child care due to an etiological diagnosis
13 months
Feasibility study of carrying out exome sequencing in the antenatal period in terms of time to deliver results
13 months
Other Outcomes (2)
Difficulties of interpretation of the exome sequencing in antenatal period
13 months
Identification of new genes responsible of fetal malformations
13 months
Study Arms (1)
90 trios (270 subjects: 90 fetus, 90 mothers, 90 fathers)
OTHERInterventions
A blood sample will be used for CGH-array and exome sequencing
Eligibility Criteria
You may qualify if:
- Father and mother of an unborn child past the age of majority
- Consent dated and signed by the mother and by the father
- Father and mother able to understand the objectives and risks of the study
- For the mother, pregnancy in progress (between 12 and 34 weeks)
- For the mother, pregnancy with the presence of a malformation on ultrasound, confirmed by a doctor from the multidisciplinary diagnostic prenatal center, entering into the indications retained for this study
- Clinical validation of the couple's eligibility by an expert for some of selected indications
- Father and mother affiliated to a social protection health
You may not qualify if:
- Identified genetic or chromosomal abnormality explaining the observed malformation
- Inability to give informations to the father and / or mother (father or mother in emergency or life-threatening situation)
- Father and / or mother under the protection of justice
- Father and / or mother under guardianship or curatorship
- Nursing woman
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
CHu de Besançon
Besançon, 25030, France
CHU de Dijon
Dijon, 21079, France
Hospices Civils de Lyon
Lyon, France
Groupe Hospitalier Region Mulhouse Et Sud Alsace
Mulhouse, 68070, France
CHU de Nancy
Nancy, 54042, France
Hôpital d'Enfants Armand-Trousseau
Paris, 75012, France
Hôpital de la Pitié Salpêtrière
Paris, 75013, France
Hôpital Necker Enfants Malades
Paris, 75743, France
CHU de Reims
Reims, 51092, France
CHU de Rennes
Rennes, 35203, France
Les Hôpitaux Universitaires de Strasbourg
Strasbourg, 67098, France
CHU de Toulouse
Toulouse, 31059, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 26, 2020
First Posted
May 28, 2020
Study Start
August 5, 2020
Primary Completion
September 1, 2021
Study Completion
September 1, 2023
Last Updated
November 13, 2020
Record last verified: 2020-11