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

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.

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