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

Completed

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

• Registration Number: NCT02512354
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03-04
• Study First Submitted: 2015-07-29
• Study First Submitted QC: 2015-07-29
• Study First Posted: 2015-07-30
• Primary Completion: 2018-10-08
• Study Completion: 2018-10-08
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-03
• Last Update Posted: 2019-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Fetus	Sample of a fragment of fetal tissue	-
Fetus	Parent's blood samples	-

Primary Outcome Measures

Name	Time	Method
Number of diagnoses not made by HTES compared with usual examinations	baseline
Number of additional diagnoses made thanks to HTES compared with the usual examinations	baseline

Trial Locations

Locations (10)

CHRU de Reims (Hôpital Maison Blanche); 🇫🇷 Reims, France

CHU de STRASBOURG (Hôpital Hautepierre); 🇫🇷 Strasbourg, France

CHU de DIJON; 🇫🇷 Dijon, France

CHU de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

CH de Mulhouse (Hôpital Emile Muller); 🇫🇷 Mulhouse, France

CHU Montpellier; 🇫🇷 Montpellier, France

CHU de NANCY; 🇫🇷 Vandoeuvre-les-nancy, France

CHU de Rouen; 🇫🇷 Rouen, France

CHU de Rennes; 🇫🇷 Rennes, France

CHRU de Tours; 🇫🇷 Tours, France