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Clinico-biological refinement of BCL11B-related disorder and identification of an episignature: A series of 20 unreported individuals.
Sabbagh, Quentin; Haghshenas, Sadegheh; Piard, Juliette; Trouvé, Chloé; Amiel, Jeanne; Attié-Bitach, Tania; Balci, Tugce; Barat-Houari, Mouna; Belonis, Alyce; Boute, Odile; Brightman, Diana S; Bruel, Ange-Line; Caraffi, Stefano Giuseppe; Chatron, Nicolas; Collet, Corinne; Dufour, William; Edery, Patrick; Fong, Chin-To; Fusco, Carlo; Gatinois, Vincent; Gouy, Evan; Guerrot, Anne-Marie; Heide, Solveig; Joshi, Aakash; Karp, Natalya; Keren, Boris; Lesieur-Sebellin, Marion; Levy, Jonathan; Levy, Michael A; Lozano, Claire; Lyonnet, Stanislas; Margot, Henri; Marzin, Pauline; McConkey, Haley; Michaud, Vincent; Nicolas, Gaël; Nizard, Mevyn; Paulet, Alix; Peluso, Francesca; Pernin, Vincent; Perrin, Laurence; Philippe, Christophe; Prasad, Chitra; Prasad, Madhavi; Relator, Raissa; Rio, Marlène; Rondeau, Sophie; Ruault, Valentin; Ruiz-Pallares, Nathalie; Sanchez, Elodie.
Afiliación
  • Sabbagh Q; Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs ¼, ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.
  • Haghshenas S; Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.
  • Piard J; University Hospital of Besançon, Department of Clinical Genetics, Besançon, France.
  • Trouvé C; University Hospital of Besançon, Department of Clinical Genetics, Besançon, France.
  • Amiel J; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Attié-Bitach T; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Balci T; University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.
  • Barat-Houari M; University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.
  • Belonis A; Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, OH; University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH.
  • Boute O; University Hospital of Lille, Department of Clinical Genetics, Lille, France.
  • Brightman DS; Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, OH.
  • Bruel AL; University Hospital of Dijon, Laboratory of Molecular Genetics and Cytogenetics, Inserm UMR 1231 GAD, Dijon, France.
  • Caraffi SG; Azienda USL-IRCCS di Reggio Emilia, Medical Genetics Unit, 42123 Reggio Emilia, Italy.
  • Chatron N; University Hospital of Lyon, Laboratory of Medical Genetics, AURAGEN Platform, Lyon, France.
  • Collet C; Robert Debré University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Dufour W; University Hospital of Lille, Department of Clinical Genetics, Lille, France.
  • Edery P; University Hospital of Lyon, Department of Clinical Genetics, Lyon, France.
  • Fong CT; University of Rochester, Department of Genetics, Rochester, NY.
  • Fusco C; Azienda USL-IRCCS di Reggio Emilia, Child Neurology and Psychiatry Unit, 42123 Reggio Emilia, Italy.
  • Gatinois V; University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.
  • Gouy E; University Hospital of Lyon, Department of Clinical Genetics, Lyon, France.
  • Guerrot AM; Rouen-Normandie University, University Hospital of Rouen, Department of Genetics, Reference Center for Developmental Disorders, Inserm UMR1245, F-76000 Rouen, France.
  • Heide S; Pitié-Salpêtrière University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Joshi A; Churchill Hospital, Department of Clinical Genetics, ERN-ITHACA, Oxford, United Kingdom.
  • Karp N; University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.
  • Keren B; Pitié-Salpêtrière University Hospital, Laboratory of Molecular Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Lesieur-Sebellin M; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Levy J; Robert Debré University Hospital, Laboratory of Cytogenetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Levy MA; Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.
  • Lozano C; University Hospital of Montpellier, Department of Immunology, Montpellier, France.
  • Lyonnet S; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Margot H; University of Bordeaux, University Hospital of Bordeaux, Department of Medical Genetics, MRGM Inserm UMR1211, F-33000 Bordeaux, France.
  • Marzin P; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • McConkey H; Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.
  • Michaud V; University of Bordeaux, University Hospital of Bordeaux, Department of Medical Genetics, MRGM Inserm UMR1211, F-33000 Bordeaux, France.
  • Nicolas G; Rouen-Normandie University, University Hospital of Rouen, Department of Genetics, Reference Center for Developmental Disorders, Inserm UMR1245, F-76000 Rouen, France.
  • Nizard M; Necker-Enfants Malades University Hospital, Department of Pediatric Endocrinology, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Paulet A; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Peluso F; Azienda USL-IRCCS di Reggio Emilia, Medical Genetics Unit, 42123 Reggio Emilia, Italy.
  • Pernin V; University of Montpellier, Department of Nephrology, Montpellier, France.
  • Perrin L; Robert Debré University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Philippe C; University Hospital of Dijon, Laboratory of Molecular Genetics and Cytogenetics, Inserm UMR 1231 GAD, Dijon, France; Hospital of Metz-Thionville, Mercy Hospital, Laboratory of Genetics, Metz, France.
  • Prasad C; University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.
  • Prasad M; University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.
  • Relator R; Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.
  • Rio M; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Rondeau S; Paris Cité University, Necker-Enfants Malades University Hospital, Department of Genomic Medicine of Rare Diseases, Imagine Institute, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  • Ruault V; Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs ¼, ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.
  • Ruiz-Pallares N; University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.
  • Sanchez E; University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.
Genet Med ; 26(1): 101007, 2024 Jan.
Article en En | MEDLINE | ID: mdl-37860968
ABSTRACT

PURPOSE:

BCL11B-related disorder (BCL11B-RD) arises from rare genetic variants within the BCL11B gene, resulting in a distinctive clinical spectrum encompassing syndromic neurodevelopmental disorder, with or without intellectual disability, associated with facial features and impaired immune function. This study presents an in-depth clinico-biological analysis of 20 newly reported individuals with BCL11B-RD, coupled with a characterization of genome-wide DNA methylation patterns of this genetic condition.

METHODS:

Through an international collaboration, clinical and molecular data from 20 individuals were systematically gathered, and a comparative analysis was conducted between this series and existing literature. We further scrutinized peripheral blood DNA methylation profile of individuals with BCL11B-RD, contrasting them with healthy controls and other neurodevelopmental disorders marked by established episignature.

RESULTS:

Our findings unveil rarely documented clinical manifestations, notably including Rubinstein-Taybi-like facial features, craniosynostosis, and autoimmune disorders, all manifesting within the realm of BCL11B-RD. We refine the intricacies of T cell compartment alterations of BCL11B-RD, revealing decreased levels naive CD4+ T cells and recent thymic emigrants while concurrently observing an elevated proportion of effector-memory expressing CD45RA CD8+ T cells (TEMRA). Finally, a distinct DNA methylation episignature exclusive to BCL11B-RD is unveiled.

CONCLUSION:

This study serves to enrich our comprehension of the clinico-biological landscape of BCL11B-RD, potentially furnishing a more precise framework for diagnosis and follow-up of individuals carrying pathogenic BCL11B variant. Moreover, the identification of a unique DNA methylation episignature offers a valuable diagnosis tool for BCL11B-RD, thereby facilitating routine clinical practice by empowering physicians to reevaluate variants of uncertain significance within the BCL11B gene.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Trastornos del Neurodesarrollo / Discapacidad Intelectual Límite: Humans Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Francia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Trastornos del Neurodesarrollo / Discapacidad Intelectual Límite: Humans Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Francia