NIPD on CFTC for Triplet Repeat Diseases (DIACCIMEX)

Non Invasive Prenatal Diagnosis on Isolated Circulating Fetal Trophoblastic Cells (CFTC) for Triplet Repeat Diseases

The purpose of this study is to develop and validate an analytical and clinical NIPD test for triplet repeat diseases by isolated circulating fetal trophoblastic cells (CFTC) analysis from maternal blood, searching for the familial mutation in families at risk of having one of the following triplet repeat diseases: Huntington's disease, Steinert Myotonic dystrophy, Fragile X syndrome, spinocerebellar ataxia (SCA) 1, 2 and 3.

Study Overview

• Status: Completed
• Conditions: Non Invasive Prenatal Diagnosis
• Intervention / Treatment: Genetic: Non invasive prenatal diagnosis

Detailed Description

Non Invasive Prenatal Diagnosis (NIPD), based on the analysis of circulating cell-free fetal DNA (cff-DNA) is very promising for early diagnosis of monogenic diseases. Such an approach is a safer alternative to invasive methods of prenatal testing (amniocentesis or choriocentesis) which entails a significant risk of miscarriage (0.5%-1%). However, technical issues related to the characteristics of cff-DNA remain and do not allow the search of all the mutations, in particular triplet expansion mutations which concern rare and incurable diseases (Huntington's disease, Steinert Myotonic dystrophy, Fragile X syndrome, SCA1, 2, 3). Indeed, the strong fragmentation and the short size of cff-DNA (143 bp) do not allow direct detection of these mutations. However, Prenatal Diagnosis (PND) requests for this group of pathologies represent the second most frequent PND indication at the national level after cystic fibrosis (ABM 2013). An alternative approach is to perform analysis on circulating fetal trophoblastic cells (CFTC) from maternal blood. Several methods have been used to isolate CFTCs from maternal blood. However, to date, no test is reliable enough for a routine application to replace invasive protocols. Recently, new enrichment systems have been optimized for circulating tumor cells (CTCs) as a liquid biopsy of cancer. Some of these new technologies can be easily applied to the isolation and characterization of CFTCs. The objective of this study is to complete our NIPD services by developing an approach on CFTC adapted to the analysis of triplet repeat diseases, which cannot be performed on cff-DNA.

It is a multicenter, prospective study for performance evaluation of a diagnostic method. The subjects included will be pregnant women between 9 and 34 weeks of gestation and their partner (future fathers). Pregnant woman and future father genotypes (sick or healthy) are known for one of the following diseases: Huntington's disease, Steinert's myotonic dystrophy, fragile X and spinocerebellar ataxias types 1, 2 or 3. The main objective is achieved by the agreement between gold standard (PND by amniocentesis or choriocentesis) and NIPD results for each pregnant woman participating in the study (the absence or presence of the mutated allele).

The couple inclusion will take place in one of the participating medical genetic centers during genetic counseling consultation for a pregnancy at risk for one of the pathologies mentioned above.

During this visit, the pregnant woman's blood sample (blood sample taken on 3 x 10 ml BCT and 5 ml on EDTA) and the future father (5 ml on EDTA) will be carried out. The duration of inclusion is the time of the visit. Blood collection of pregnant women on cell-free DNA "Blood Collection Tubes" (BCT) to screen CFTCs will be addressed to the Human Rare Circulating Cells Laboratory (LCCRH). The molecular analysis of the CFTC isolated by the LCCRH as well as the genomic DNA extraction and analysis (from the 5 ml of blood on EDTA) of the couple will be carried out by the Laboratory of Molecular Genetics (LGM) located in the same Building (IURC - Montpellier University Hospital).

The analysis performed on a simple maternal blood test will allow to determine whether the future child is affected or not by the inherited disease. With this new NIPD approach, there could be a 50% decrease in the use of the invasive method for PND. This analysis can be offered to women carrying foetuses at risk for triplet repeat diseases. Finally, this approach can be applied to any monogenic diseases by CFTCs isolation automation from maternal blood.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • CHU Bordeaux
  • Montpellier, France, 34295
    • CHU Montpellier
  • Nice, France, 06202
    • CHU Nice
  • Nîmes, France, 30029
    • CHU Nimes
  • Rennes, France, 35203
    • CHU Rennes
  • Saint-Brieuc, France, 22027
    • CH Saint Brieuc
  • Schiltigheim, France, 67303
    • CHU Strasbourg
  • Toulouse, France, 31059
    • Chu Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• older than 18 years old
• pregnant woman between 9 and 34 weeks of gestation
• Couple at risk (based on family history or echographic findings) for one of the following diseases: Huntington's disease, Steinert's myotonic dystrophy, fragile X and spinocerebellar ataxias 1, 2 or 3
• Written informed consent was obtained for the study
• Prenatal diagnosis has been programmed for the current pregnancy during which maternal blood is collected
• Couple molecular diagnosis results for one of the following diseases (Huntington's disease, Steinert's myotonic dystrophy, fragile X and spinocerebellar ataxias 1, 2 or 3 ) MUST BE AVAILABLE.

Exclusion Criteria:

• Couple Genomic DNA are unavailable
• Subjects at risk of transmitting the family disease, but not wishing to know their molecular status
• individuals under guardianship by court order

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Couple at risk of transmitting a triplet-repeat disease; Expectant couple (pregnant woman between 9 and 34 weeks of gestation and her spouse) at risk of transmitting a triplet-repeat related genetic disease among Huntington disease, Myotonic Dystrophy type 1, Fragile X syndrome, Spinocerebellar Ataxia type 1, Spinocerebellar Ataxia type 2, Spinocerebellar Ataxia type 3	Genetic: Non invasive prenatal diagnosis; Search for the familial mutation on isolated circulating fetal trophoblastic cells from maternal blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance rate between cell-based genetic non invasive prenatal test and gold standard prenatal test (choriocentesis or amniocentesis).	Analysis of the concordance of the prenatal results obtained by our new NIPD (Non-Invasive Prenatal Diagnosis) approach and those blindly obtained during the gold-standard prenatal genetic test will be carried out for each pregnant woman participating in the study.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non Invasive Prenatal Diagnostic test failure rate.	Count of the women enrolled for whom NIPD test will be inconclusive (because of insufficient circulating fetal cells isolation or allele drop out making accurate haplotyping impossible).	30 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Marie Claire VINCENT, PhD-PharmaD, University Hospital, Montpellier

Publications and helpful links

General Publications

• Cayrefourcq L, Vincent MC, Pierredon S, Moutou C, Imbert-Bouteille M, Haquet E, Puechberty J, Willems M, Liautard-Haag C, Molinari N, Zordan C, Dorian V, Rooryck-Thambo C, Goizet C, Chaussenot A, Rouzier C, Boureau-Wirth A, Monteil L, Calvas P, Miry C, Favre R, Petrov Y, Khau Van Kien P, Le Boette E, Fradin M, Alix-Panabieres C, Guissart C. Single Circulating Fetal Trophoblastic Cells Eligible for Non Invasive Prenatal Diagnosis: the Exception Rather than the Rule. Sci Rep. 2020 Jun 17;10(1):9861. doi: 10.1038/s41598-020-66923-9.
• Liautard-Haag C, Durif G, VanGoethem C, Baux D, Louis A, Cayrefourcq L, Lamairia M, Willems M, Zordan C, Dorian V, Rooryck C, Goizet C, Chaussenot A, Monteil L, Calvas P, Miry C, Favre R, Le Boette E, Fradin M, Roux AF, Cossee M, Koenig M, Alix-Panabiere C, Guissart C, Vincent MC. Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach. Sci Rep. 2022 Jul 6;12(1):11423. doi: 10.1038/s41598-022-15307-2.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: February 23, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Huntington's Disease; Myotonic Dystrophy Type 1; Non Invasive Prenatal Diagnosis (NIPD); Circulating Fetal Trophoblastic Cells (CFTC); Fragile X syndrome; Spinocerebellar Ataxia type 1; Spinocerebellar Ataxia type 2; Spinocerebellar Ataxia type 3
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Mental Disorders; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Congenital Abnormalities; Movement Disorders; Heredodegenerative Disorders, Nervous System; Intellectual Disability; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Basal Ganglia Diseases; Spinal Cord Diseases; Dyskinesias; Sex Chromosome Disorders; Chromosome Disorders; Chorea; Cerebellar Diseases; Cerebellar Ataxia; Muscular Dystrophies; Myotonic Disorders; Spinocerebellar Degenerations; Ataxia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; X-Linked Intellectual Disability; Myotonic Dystrophy; Fragile X Syndrome; Huntington Disease; Spinocerebellar Ataxias; Machado-Joseph Disease
• Other Study ID Numbers: RECHMPL17_0021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No