Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders

Sponsor
Assistance Publique - Hôpitaux de Paris
Study ID
NCT06147414
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Blood sample — BIOLOGICAL
    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.

Study Details

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.

Key Dates

First listed
Nov 27, 2023
Start date
Oct 23, 2024
Status verified
Apr 2026
Primary completion
May 31, 2027
Completion
May 31, 2027

Study Design

Enrollment
550 participants (estimated)

Arms

  • Arm: pregnant women undergoing invasive PND in a context of family history of SGD
    SGD-NIPD will be proposed by CPDPN recruitment centres to pregnant women undergoing invasive PND in a context of family history of SGD because of parental pathogenic mutation.s in one of the following gene: HBB, CFTR, FMR1, SMN1, DMPK, DMD, NF1, HTT, F8, F9, GCK, L1CAM, PKHD1.
  • Arm: pregnant women undergoing prenatal counselling in a context of maternal history of diabetes MODY-GCK

Primary Outcome Measure

% of affected/unaffected fetuses that were correctly classified as affected/unaffected [ Time Frame: 1 day ]

Central Contacts

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