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

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

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.

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.

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