Boris Keren1, Delphine Héron2, Solveig Heide3, Myrtille Spentchian2, Stéphanie Valence4, Julien Buratti1, Corinne Mach1, Elodie Lejeune1, Valérie Olin1, Marta Massimello2, Daphné Lehalle2, Linda Mouthon2, Sandra Whalen5, Anne Faudet2, Cyril Mignot2, Catherine Garel6, Eleonore Blondiaux6, Mathilde Lefebvre7, Geneviève Quenum-Miraillet8, Sandra Chantot-Bastaraud8, Mathieu Milh9, Florence Bretelle10, Vincent des Portes11, Laurent Guibaud12, Audrey Putoux13, Vassili Tsatsaris14, Marta Spodenkiewic15, Valérie Layet16, Rodolphe Dard17, Laurent Mandelbrot18, Agnès Guet19, Sébastien Moutton20, Magali Gorce21, Mathilde Nizon22, Marie Vincent22, Claire Beneteau22, Marie-Amélie Rocchisanni23, Alexandra Benachi24, Julien Saada24, Tania Attié-Bitach25, Lucie Guilbaud26, Paul Maurice26, Stéphanie Friszer26, Jean-Marie Jouannic26, Thierry Billette de Villemeur4, Marie-Laure Moutard4. 1. UF de Génomique du Développement, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP Sorbonne Université, Paris, France. 2. UF de Génétique Médicale et CRMR « Déficience intellectuelle », Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP Sorbonne Université, Paris, France. 3. UF de Génétique Médicale et CRMR « Déficience intellectuelle », Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP Sorbonne Université, Paris, France. solveig.heide@aphp.fr. 4. Service de Neurologie Pédiatrique, Hôpital Armand Trousseau, APHP Sorbonne Université, Paris, France. 5. Service de Génétique Clinique, Hôpital Armand Trousseau, APHP Sorbonne Université, Paris, France. 6. Service de Radiologie Pédiatrique, Hôpital Armand Trousseau, HUEP, APHP Sorbonne Université, Paris, France. 7. Service de Foetopathologie, Hôpital Armand Trousseau, HUEP, APHP Sorbonne Université, Paris, France. 8. Service de Cytogénétique, Hôpital Armand Trousseau, HUEP, APHP Sorbonne Université, Paris, France. 9. Service de Neurologie Pédiatrique, Hôpital La Timone, APHM, Marseille, France. 10. Service de Gynécologie Obstétrique, Hôpital Nord, APHM, Aix-Marseille Université, Marseille, France. 11. Service de Neurologie Pédiatrique, Hospices Civils de Lyon, Bron, France. 12. Service de Radiologie Pédiatrique, Hospices Civils de Lyon, Bron, France. 13. Service de Génétique Clinique, Hospices Civils de Lyon, Bron, France. 14. Service de Gynécologie Obstétrique, Hôpital Cochin, Paris, France. 15. Service de Génétique Clinique, CHU de Reims, Reims, France. 16. Service de Génétique Clinique, Hôpital du Havre, Le Havre, France. 17. Service de Génétique Clinique, Hôpital de Poissy, Poissy, France. 18. Service de Gynécologie Obstétrique, APHP, Université de Paris, Hôpital Louis Mourier, Colombes, France. 19. Service de Pédiatrie, APHP, Hôpital Louis Mourier, Colombes, France. 20. Service de Génétique Clinique, CHU de Dijon, Dijon, France. 21. Service de Génétique Clinique, CHU d'Angers, Angers, France. 22. Service de Génétique Clinique, CHU de Nantes, Nantes, France. 23. Service de Médecine Néonatale, Hôpital Cochin, APHP, Paris, France. 24. Service de Gynécologie-Obstétrique, Hôpital Antoine Béclère, APHP, Université Paris Saclay, Clamart, France. 25. Embryofoetopathologie, Service Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France. 26. Fetal Medicine Département, Hôpital Armand Trousseau, APHP, Sorbonne Université, Paris, France.
Abstract
PURPOSE: Abnormality of the corpus callosum (AbnCC) is etiologically a heterogeneous condition and the prognosis in prenatally diagnosed cases is difficult to predict. The purpose of our research was to establish the diagnostic yield using chromosomal microarray (CMA) and exome sequencing (ES) in cases with prenatally diagnosed isolated (iAbnCC) and nonisolated AbnCC (niAbnCC). METHODS: CMA and prenatal trio ES (pES) were done on 65 fetuses with iAbnCC and niAbnCC. Only pathogenic gene variants known to be associated with AbnCC and/or intellectual disability were considered. RESULTS: pES results were available within a median of 21.5 days (9-53 days). A pathogenic single-nucleotide variant (SNV) was identified in 12 cases (18%) and a pathogenic CNV was identified in 3 cases (4.5%). Thus, the genetic etiology was determined in 23% of cases. In all diagnosed cases, the results provided sufficient information regarding the neurodevelopmental prognosis and helped the parents to make an informed decision regarding the outcome of the pregnancy. CONCLUSION: Our results show the significant diagnostic and prognostic contribution of CMA and pES in cases with prenatally diagnosed AbnCC. Further prospective cohort studies with long-term follow-up of the born children will be needed to provide accurate prenatal counseling after a negative pES result.
PURPOSE: Abnormality of the corpus callosum (AbnCC) is etiologically a heterogeneous condition and the prognosis in prenatally diagnosed cases is difficult to predict. The purpose of our research was to establish the diagnostic yield using chromosomal microarray (CMA) and exome sequencing (ES) in cases with prenatally diagnosed isolated (iAbnCC) and nonisolated AbnCC (niAbnCC). METHODS: CMA and prenatal trio ES (pES) were done on 65 fetuses with iAbnCC and niAbnCC. Only pathogenic gene variants known to be associated with AbnCC and/or intellectual disability were considered. RESULTS: pES results were available within a median of 21.5 days (9-53 days). A pathogenic single-nucleotide variant (SNV) was identified in 12 cases (18%) and a pathogenic CNV was identified in 3 cases (4.5%). Thus, the genetic etiology was determined in 23% of cases. In all diagnosed cases, the results provided sufficient information regarding the neurodevelopmental prognosis and helped the parents to make an informed decision regarding the outcome of the pregnancy. CONCLUSION: Our results show the significant diagnostic and prognostic contribution of CMA and pES in cases with prenatally diagnosed AbnCC. Further prospective cohort studies with long-term follow-up of the born children will be needed to provide accurate prenatal counseling after a negative pES result.
Entities:
Keywords:
agenesis of the corpus callosum; anomaly of the corpus callosum; exome sequencing; prenatal; prenatal exome sequencing
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