Clinical trial NCT02512354: Contribution of High-throughput Exome Sequencing in the Diagnosis of the Cause Fetal Polymalformation Syndromes
Official title: Contribution of High-throughput Exome Sequencing in Fetopathology
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fetuses With at Least 2 Malformations, and no Diagnosis After Fetopathological and Radiological Examinations
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2015-07-30
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Fetuses With at Least 2 Malformations, and no Diagnosis After Fetopathological and Radiological Examinations

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of additional diagnoses made thanks to HTES compared with the usual examinations
timeFrame: baseline
measure: Number of diagnoses not made by HTES compared with usual examinations
timeFrame: baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Dijon
country: France
facility: CHU de DIJON
city: Montpellier
country: France
facility: CHU Montpellier
city: Mulhouse
country: France
facility: CH de Mulhouse (Hôpital Emile Muller)
city: Reims
country: France
facility: CHRU de Reims (Hôpital Maison Blanche)
city: Rennes
country: France
facility: CHU de Rennes
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: CHU de STRASBOURG (Hôpital Hautepierre)
city: Tours
country: France
facility: CHRU de Tours
city: Vandoeuvre-les-nancy
country: France
facility: CHU de NANCY
Study officials:
References: