ANDDI-PRENATOME - Feasibility Study for a " Fast " Pangenomic High Throughput Sequencing Analysis in Prenatal Diagnosis

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.

Conditions

• Prenatal
• Genome-wide High Throughput Sequencing

Interventions

BIOLOGICAL

Invasive fetal sampling, blood sampling of mother and father

to perform an exome sequencing analysis in trio

BIOLOGICAL

blood sampling from the mother to recover the circulating cell free fetal DNA

to perform a sequencing analysis of the genome of circulating free fetal DNA

OTHER

Parent interviews (optional organizational study)

Interview with a sociologist or psychologist to explore perceptions of ES and the impact of the results, expectations regarding certain types of results not currently available, the emotional situation, and position regarding the continuation of the pregnancy At 4 different times: at inclusion, at the time of the CGA-array results, at the time of the ES results and at a distance from the ES results

OTHER

parent questionnaire (optional organizational study)

To evaluate the experience, perceptions, the impact of the analyses on the decision, satisfaction and concerns regarding the ES and its results, opinions on certain types of results not currently available, as well as anxiety and possible psychological distress At 4 different points in time: at inclusion, at the delivery of the CGA-array results, at the delivery of the ES results and at a distance from the delivery of the ES results

OTHER

professional interviews (optional organizational study)

interview to understand how the decision is formed

OTHER

Focus group for professionals (optional organizational study)

interview to specify whether variants of unknown significance) VUS will potentially be returned to the clinicians, or even to the patient via the clinician.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon

  lead OTHER

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-06-20

Primary Completion

2021-12-20

Completion

2024-01-25

Countries

• France

Study Locations