Non-invasive Prenatal Diagnosis of Monogenic Disorders by Linked-reads Technology

NCT03622892 | Completed

• 1 other identifier: NID ( 29BRC18.0055)
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 6

Brief Summary

Description of the presence of cell-free fetal DNA in maternal plasma allowed the possibility of non-invasive prenatal diagnosis. Whereas detection of paternally-inherited alleles is straightforward and being quickly implemented in routine, detection of maternally-inherited alleles remains challenging. To date, the main approach that is being developped, called Relative Haplotype Dosage Analysis, relies on the identification of an allelic imbalance between the mother's wild-type and mutant alleles, relative to the fetal's contribution. This approach therefore requires the study of a propositus to identify the morbid haplotype, which is not always possible in the context of an ongoing pregnancy. In this study, we aim to evaluate the contribution of new technologies, such as linked-read Sequencing, to allow direct identification of parental haplotype in the context of non-invasive prenatal diagnosis.

Conditions

Cystic Fibrosis

Keywords

Non Invasive Prenatal Diagnosis

Outcome Measures

Primary Outcomes (1)

• Non-invasive Prenatal Diagnosis of Monogenic Disorders

  Development of a robust and standardized NIPD protocol relying on Relative Haplotype Dosage Analysis after deciphering of parental haplotype by Linked-Read Sequencing

  3 years

Secondary Outcomes (1)

• Description of Circulating Fetal Cells

  3 years

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Couples at 25% risk of transmitting Cystic Fibrosis and asking for prenatal diagnosis for this indication in the pluridisciplinary centers of Brest, Nantes, Dijon or Rouen University Hospitals, France.

You may qualify if:

• Pregnancies at 25% risk of being affected by Cystic Fibrosis with previously identified pathogenic variants
• Couple asking for invasive prenatal diagnosis
• Pregnancy at 8 weeks of gestation or later

You may not qualify if:

• Couple not asking for prenatal diagnosis
• No signed consent obtained

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (6)

CHRU de Brest

Brest, 29609, France

Location

CHRU de Dijon

Dijon, 21079, France

Location

CHU de Nantes

Nantes, 44093, France

Location

CHU de Rennes

Rennes, 35000, France

Location

CHU de Rouen

Rouen, 76031, France

Location

CH Saint Brieuc

Saint-Brieuc, 22000, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Parental DNA Maternal cell-free DNA

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Mathilde Pacault, MD

  CHU de Brest

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 9, 2018
• Study Start: October 18, 2018
• Primary Completion: September 5, 2022
• Study Completion: September 5, 2022
• Last Updated: June 26, 2026

Record last verified: 2026-06

Locations

FR (6)