NIPD on cffDNA for Triplet Repeat Diseases

NCT04698551 | Unknown

• 1 other identifier: RECHMPL20_0441
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purprose of this study is to develop and validate an analytical NIPD test for triplet repeat disesases by NGS 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, Myotonic dystrophy, Fragile X syndrome.. A comparison of two 3rd generation long fragment DNA sequencing techniques will be performed. These methods are based of the phasing techniques of parental haplotypes without the proband.

Conditions

Myotonic Dystrophy 1; Huntington Disease; Fragile X Syndrome

Keywords

Non Invasive Prenatal Diagnosis (NIPD); Circulating Fetal DNA (CFTC); triplet expansion diseases

Outcome Measures

Primary Outcomes (1)

• Concordance rate between cell free foetal DNA based genetic

  t is a qualitative analysis : for each sample of each pregnant women, the presence of absence of a mutation (or morbid haplotype) responsible for a triplet expansion will be determined from maternal blood (Non invasive Pregnancy Diagnosis). the result could be : health fetus, affected fetus or non conclusive result (i.e. the analysis didn't allow to conclude if the fetus would be affected or not) Then, determination of the 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

  36 months

Secondary Outcomes (1)

• Qualitative process to define the differents steps to analysis of the cell free foetal DNA

  36 months

Study Arms (1)

16 pregnant women and their spouses

16 pregnant women and their spouses

Genetic: Non invasive prenatal diagnosis

Interventions

Non invasive prenatal diagnosis GENETIC

Search for the familial mutation involved in DPN requests from phasing of parental haplotypes by 3rd generation long-fragment DNA sequencing techniques coupled with targeted sequencing of free circulating DNA from maternal plasma.

16 pregnant women and their spouses

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Retrospective study of 16 couples at risk of transmitting a disease with triplet expansions (Myotonic dystrophy of Steinert, Huntington's disease, FRAXA) Couples undergoing prenatal diagnosis for a monogenic disease caused by dynamic mutation

You may qualify if:

• 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
• Written informed consent was obtained for DIACCIMEX study and mentionned "authorization for use for further studies on familial pathology. Indeed, the DNA can be used anonymized for the development of new analyzes of non-invasive prenatal diagnosis".
• Prenatal diagnosis has been done for the pregnancy during which maternal blood has been 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Agence de La Biomédecine: collaborator

Study Sites (1)

CHU Montpellier

Montpellier, 34295, France

Location

Related Publications (1)

• 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.

  PMID: 35794169 DERIVED

MeSH Terms

Conditions

Myotonic Dystrophy; Huntington Disease; Fragile X Syndrome

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Marie Claire VINCENT, PhD-PharmaD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: January 7, 2021
• Study Start: September 1, 2020
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: January 7, 2021

Record last verified: 2020-09

Locations

FR (1)