Contribution of High-throughput Exome Sequencing in the Diagnosis of the Cause Fetal Polymalformation Syndromes (FOETEX)

Contribution of High-throughput Exome Sequencing in Fetopathology

This research concerns the contribution of a new examination, high-throughput exome sequencing, in the diagnosis of the cause of polymalformative fetal syndromes. With currently available examinations, the causes of polyformative syndromes, which correspond to the association of several congenital malformations with varying degrees of severity in different organs, remain unknown in a large number of cases.

High-throughput exome sequencing (HTES) is a diagnostic tool that allows the simultaneous analysis of all of the coding parts of DNA. This examination has already shown its superior diagnostic capability in every post-natal diagnostic context, in particulier in infants with malformations associated or not with intellectual deficiency. Its contribution has not yet been studied in a large number of fetuses with polymalformations. To investigate the usefulness of HTES, we propose to carry out the examination in 100 fetuses with polymalformations, as well as the usual examinations including chromosomal microarray analysis and possibly the study of specific genes that may explain these malformations. A blood sample will be taken from both parents to allow interpretation of the results.

Study Overview

• Status: Completed
• Conditions: Fetuses With at Least 2 Malformations, and no Diagnosis After Fetopathological and Radiological Examinations
• Intervention / Treatment: Other: Sample of a fragment of fetal tissue; Other: Parent's blood samples

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • CHU de Clermont-Ferrand
  • Dijon, France, 21079
    • CHU de Dijon
  • Montpellier, France, 34000
    • Chu Montpellier
  • Mulhouse, France, 68070
    • CH de Mulhouse (Hôpital Emile Muller)
  • Reims, France, 51092
    • CHRU de Reims (Hôpital Maison Blanche)
  • Rennes, France, 35203
    • CHU de Rennes
  • Rouen, France, 76000
    • Chu de Rouen
  • Strasbourg, France, 67098
    • CHU de STRASBOURG (Hôpital Hautepierre)
  • Tours, France, 37000
    • CHRU de Tours
  • Vandoeuvre-les-nancy, France, 54511
    • Chu de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Fetuses With at Least 2 Malformations, and no Diagnosis After Fetopathological and Radiological Examinations

Description

Inclusion Criteria:

• Fetus with at least 2 malformations, with no diagnosis (or several low-certainty diagnostic hypotheses, which require several molecular examinations) after fetopathological and radiological examinations
• Written consent from both parents
• Possibility to obtain samples from both parents

Exclusion Criteria:

• Refusal of parents to take part in the study
• Parents without National Health Insurance cover
• Parents under guardianship or in custody
• Impossibility to obtain samples from both parents
• Diagnostic hypothesis considered highly probable for which a molecular test cheaper that HTES is available

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fetus	Other: Sample of a fragment of fetal tissue; Other: Parent's blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of additional diagnoses made thanks to HTES compared with the usual examinations	baseline
Number of diagnoses not made by HTES compared with usual examinations	baseline

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2015
• Primary Completion (Actual): October 8, 2018
• Study Completion (Actual): October 8, 2018

Study Registration Dates

• First Submitted: July 29, 2015
• First Submitted That Met QC Criteria: July 29, 2015
• First Posted (Estimate): July 30, 2015

Study Record Updates

• Last Update Posted (Actual): December 5, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease
• Other Study ID Numbers: THEVENON PHRC I 2014