Official Title
ANDDI-PRENATOME - Feasibility Study for a " Fast " Pangenomic High Throughput Sequencing Analysis in Prenatal Diagnosis
Brief Title
ANDDI-PRENATOME - Feasibility Study for a " Fast " Pangenomic High Throughput Sequencing Analysis in Prenatal Diagnosis
Protocol ID
NCT03964441
Lead Sponsor
Centre Hospitalier Universitaire Dijon
Brief Summary
Prenatal diagnosis of genetic diseases is a real medical challenge. The discovery of
antenatal abnormalities on ultrasound is frequent (5 to 10% of pregnancies), and when an
abnormalities is seen on ultrasound, it raises the possibility of an underlying
developmental anomaly. Currently, in France, when abnormalities are discovered with an
ultrasound scan, the etiological diagnosis is based on additional imaging tests (cerebral
MRI, 3D bone tomography, fetal CT, fetal CT) or diagnostic tests such as invasive
chorionic villus sampling, amniocentesis or fetal blood for infectious, metabolic,
immunological and genetic investigations (standard karyotype, FISH (fluorescence in situ
hybridization) for the rapid detection of aneuploidy, Chromosome Analysis on DNA Chip
(ACPA or CGH-array) and possible sequencing of targeted genes when they are available
within a time frame compatible with pregnancy). NIPT (Non-invasive prenatal testing) on
cell free fetal DNA circulating in maternal blood has more limited indications, allowing,
from an early stage of pregnancy, the determination of fetal sex and fetal rhesus factor
and the search for aneuploidy.
However, establishing an etiological diagnosis during pregnancy has many benefits for the
parents: clarifying the cause, obtaining a more precise prognosis to determine future
management and outcome of the pregnancy, and establishing the risks of recurrence.
Over the past decade, medical genetics has undergone a real technological revolution,
leading to the development of high throughput genome-wide, exome (ES) and genome (GS)
sequencing. However, few countries have currently embarked on ES/GS in prenatal care, due
to the constraints of time and the difficulty of interpreting genomic data when the
clinical data is limited to antenatal imaging data.
In 2016, France launched the France Medicine Genomics 2025 Plan (PFMG2025) to deploy GS,
particularly in the diagnosis of rare diseases. It is thus becoming essential to define
the modalities of prescription of this testing, in particular during prenatal diagnosis.
In parallel, from the first publications, the applications of genomic analysis on
circulating fetal DNA seem to be able to extend to genome sequencing for research of SNVs
responsible for developmental diseases.
The AnDDI-rares health network therefore proposes this ANDDI-PRENATOME pilot project to
study the feasibility of a "rapid" analysis of ES in prenatal diagnosis from 61 fetuses
with ultrasound abnormalities, as a first step before considering future
cost-effectiveness (PRME) or care system performance (PREPS) studies in conjunction with
the PFMG2025.
Study Period
-
Enrollment Count
149 participants
Eligibility Criteria
Inclusion Criteria:
- Pregnant women with antenatal discovery of at least two obstetric ultrasound
abnormalities (2 major malformations, or 1 major malformation and 1 minor
malformation, or 1 isolated malformation with a high probability of a genetic
condition) : who undergo invasive antenatal sampling for CGH-array diagnosis ; who
has already had an invasive antenatal sampling for the diagnosis of CGH-array and
for which the fetal CGH-array has been found to be normal (sufficient fetal DNA or
amniotic fluid should be available to allow exome sequencing to be performed without
further amniotic fluid puncture).
- Pregnant woman and father aged 18 years or more
- Written consent provided by the pregnant woman and the father of the fetus
- Possibility of sufficient fetal specimen (amniotic fluid or fetal blood) to collect
an additional sample for the pilot project
- Possibility of sampling the pregnant woman and the father of the foetus (peripheral
blood)
- Pregnant woman and father of the fetus able to understand the study
Pilot Organizational Study:
In addition to the inclusion & exclusion criteria of the main study:
- Pregnant woman and biological father of fetus who provided oral consent to be
interviewed
- Professionals (obstetrician, midwife, geneticist, biologist) agreeing to be
interviewed
Exclusion Criteria:
- Diagnostic hypothesis considered highly probable that can be confirmed by an
available molecular or cytogenetic test with a lower cost than ES (e. g. 22q11
microdeletion) or high suspicion of fetal infection (e. g. toxoplamosis
seroconversion)
- Refusal of pregnant woman or father of fetus to participate in the study
- Pregnancy earlier than 15 weeks of amenorrhea or later than 34 weeks of amenorrhea
- Pregnant woman and father of the foetus not covered by the national health insurance
system
- Pregnant woman and/or father of the fetus under partial judicial protection
Filters
Prenatal
Genome-wide High Throughput Sequencing
COMPLETED
ADULT
OLDER_ADULT