Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders

Summary

Cell-free fetal DNA (cffDNA) is present in the maternal blood from the early first trimester of gestation and makes up 5%-20% of the total circulating cell-free DNA (cfDNA) in maternal plasma. Its presence in maternal plasma has allowed development of noninvasive prenatal diagnosis for single-gene disorders (SGD-NIPD). This can be performed from 9 weeks of amenorrhea and offers an early, safe and accurate definitive diagnosis without the miscarriage risk associated with invasive procedures. One of the major difficulties is distinguishing fetal genotype in the high background of maternal cfDNA, which leads to several technical and analytical challenges. Besides, unlike noninvasive prenatal testing for aneuploidy, NIPD for monogenic diseases represent a smaller market opportunity, and many cases must be provided on a bespoke, patient- or disease-specific basis. As a result, implementation of SGD-NIPD remained sparse, with most testing being delivered in a research setting.

The present project aims to take advantage of the unique French collaborative network to make SGD-NIPD possible for theoretically any monogenic disorder and any family.

Conditions

• Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including
• Sickle Cell Disease
• Cystic Fibrosis
• Fragile X Syndrome
• Proximal Spinal Muscular Atrophy
• Myotonic Dystrophy
• Muscular Dystrophy, Duchenne
• Muscular Dystrophy, Becker
• Neurofibromatosis-Noonan Syndrome
• Huntington Disease
• Hemophilia A
• Hemophilia B
• MODY2 Diabetes
• X-Linked Hydrocephalus
• Autosomal Recessive Polycystic Kidney Disease

Interventions

BIOLOGICAL

Blood sample

A blood sample (50 ml) will be taken in care of prenatal diagnosis and 40 ml will be used for study. The 40 mL of blood needed for the research will be collected on BCT tubes (4 tubes). During the study, in centers, the plasma samples will be stored at room temperature and will be sent to the laboratory within 24 hours (no centrifugation in centers). The plasma samples will be then temporarily stored at -80°C in each co-investigating laboratory under the supervision of lab supervisor until the analysis. cfDNA will be extracted from the whole plasma sample before each sequencing run and stored à +4°C until the cfDNA sequencing.

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin

  collaborator OTHER

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Juliette NECTOUX, MD,PhD · Assistance Publique - Hôpitaux de Paris

• Thierry BIENVENU · Assistance Publique - Hôpitaux de Paris

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-10-23

Primary Completion

2027-05-31

Completion

2027-05-31

Countries

• France

Study Locations