Whole Exome Sequencing in Prenatal Diagnosis of Agenesis of the Corpus Callosum

NCT ID: NCT03600792

Last Updated: 2021-01-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 31 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-08-28
• Study Completion Date: 2019-10-19

Brief Summary

Agenesis of the corpus callosum (ACC) is one of the most frequent cerebral malformations and is now diagnosed prenatally in most cases. Prenatal counseling is then challenging because of uncertain neurodevelopmental outcome, depending on the genetic cause of ACC. Our purpose is to evaluate the feasibility of sequencing known genes responsible for ACC by whole exome sequencing (WES) in trio (fetus and both parents) when ACC is diagnosed during the pregnancy, in order to provide complete and loyal information on the intellectual prognosis for the fetus.

Detailed Description

Agenesis of the corpus callosum (ACC) is one of the most frequent cerebral malformations. The neurodevelopmental outcome of patients with ACC is extremely variable, ranging from normal intelligence to severe intellectual disability (ID). When ACC is discovered during the prenatal period, prenatal counseling is challenging because of this uncertain neurodevelopmental outcome. Currently, only chromosomal analyses are performed in cases of prenatal diagnoses, which are expected to bring the diagnosis in only few cases. No molecular studies of genes implied in ACC with or without ID are performed. Then, the couples are in the difficult situation of continuing or interrupting the pregnancy without complete information about the aetiology of ACC.

All patients will have a consultation with an obstetrician and consultations with a paediatric neurologist and a geneticist. The geneticist will explain WES and its issues. Both parents will have to provide informed consent for the study.

Conditions

Fetal Agenesis of the Corpus Callosum (ACC)

Study Design

• Observational Model Type: FAMILY_BASED
• Study Time Perspective: PROSPECTIVE

Interventions

whole exome sequencing (WES)

WES analysis will be performed in the "UF de Génomique du Développement" (APHP, Pitié-Salpêtrière hospital), using DNA extracted from amniotic fluid for the foetus (also used for chromosomal studies) and DNA extracted from peripheral blood for both parents. There will be no supplemental invasive sampling for this study. The result of WES will be returned during a consultation with the geneticist and the associated prognosis will be explained in case of molecular diagnosis

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old
• ACC diagnosed prenatally during the 2nd trimester of pregnancy, confirmed by ultrasound by a referee
• Fetal sample (amniotic fluid, 10 ml) et blood samples of both parents (2 tubes of 5 ml EDTA)
• Covered by social security
• Written consent obtain for routine and research genetic analysis

Exclusion Criteria

• Refusal to participate from one or both parents
• Pregnancies obtained with gamete donation (trio sequencing not feasible)
• If one parent is not available (trio sequencing not feasible)
• Inability to understand the given information
• One or both parents under juridical protection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Héron Delphine, MD

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Countries

France

Other Identifiers

NI18011J

Identifier Type: -

Identifier Source: org_study_id