Clinico-biological refinement of BCL11B-related disorder and identification of an episignature: A series of 20 unreported individuals.

BCL11B Epigenetic signature Neurodevelopmental delay T cells

Journal

Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831

Informations de publication

Date de publication:
17 Oct 2023
Historique:
received: 26 06 2023
revised: 09 10 2023
accepted: 09 10 2023
pubmed: 20 10 2023
medline: 20 10 2023
entrez: 20 10 2023
Statut: aheadofprint

Résumé

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. 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. 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 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.

Identifiants

DOI: 10.1016/j.gim.2023.101007 PMID: 37860968
pubmed: 37860968
pii: S1098-3600(23)01023-7
doi: 10.1016/j.gim.2023.101007
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101007

Informations de copyright

Copyright © 2023 American College of Medical Genetics and Genomics. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of Interest The authors declare no conflicts of interest.

Auteurs

Quentin Sabbagh (Q)

Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.

Sadegheh Haghshenas (S)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.

Juliette Piard (J)

University Hospital of Besançon, Department of Clinical Genetics, Besançon, France.

Chloé Trouvé (C)

University Hospital of Besançon, Department of Clinical Genetics, Besançon, France.

Jeanne 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.

Tania 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.

Tugce Balci (T)

University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.

Mouna Barat-Houari (M)

University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.

Alyce 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.

Odile Boute (O)

University Hospital of Lille, Department of Clinical Genetics, Lille, France.

Diana S Brightman (DS)

Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, OH.

Ange-Line Bruel (AL)

University Hospital of Dijon, Laboratory of Molecular Genetics and Cytogenetics, Inserm UMR 1231 GAD, Dijon, France.

Stefano Giuseppe Caraffi (SG)

Azienda USL-IRCCS di Reggio Emilia, Medical Genetics Unit, 42123 Reggio Emilia, Italy.

Nicolas Chatron (N)

University Hospital of Lyon, Laboratory of Medical Genetics, AURAGEN Platform, Lyon, France.

Corinne Collet (C)

Robert Debré University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

William Dufour (W)

University Hospital of Lille, Department of Clinical Genetics, Lille, France.

Patrick Edery (P)

University Hospital of Lyon, Department of Clinical Genetics, Lyon, France.

Chin-To Fong (CT)

University of Rochester, Department of Genetics, Rochester, NY.

Carlo Fusco (C)

Azienda USL-IRCCS di Reggio Emilia, Child Neurology and Psychiatry Unit, 42123 Reggio Emilia, Italy.

Vincent Gatinois (V)

University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.

Evan Gouy (E)

University Hospital of Lyon, Department of Clinical Genetics, Lyon, France.

Anne-Marie Guerrot (AM)

Rouen-Normandie University, University Hospital of Rouen, Department of Genetics, Reference Center for Developmental Disorders, Inserm UMR1245, F-76000 Rouen, France.

Solveig Heide (S)

Pitié-Salpêtrière University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Aakash Joshi (A)

Churchill Hospital, Department of Clinical Genetics, ERN-ITHACA, Oxford, United Kingdom.

Natalya Karp (N)

University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.

Boris Keren (B)

Pitié-Salpêtrière University Hospital, Laboratory of Molecular Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Marion 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.

Jonathan Levy (J)

Robert Debré University Hospital, Laboratory of Cytogenetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Michael A Levy (MA)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.

Claire Lozano (C)

University Hospital of Montpellier, Department of Immunology, Montpellier, France.

Stanislas 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.

Henri Margot (H)

University of Bordeaux, University Hospital of Bordeaux, Department of Medical Genetics, MRGM Inserm UMR1211, F-33000 Bordeaux, France.

Pauline 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.

Haley McConkey (H)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.

Vincent Michaud (V)

University of Bordeaux, University Hospital of Bordeaux, Department of Medical Genetics, MRGM Inserm UMR1211, F-33000 Bordeaux, France.

Gaël Nicolas (G)

Rouen-Normandie University, University Hospital of Rouen, Department of Genetics, Reference Center for Developmental Disorders, Inserm UMR1245, F-76000 Rouen, France.

Mevyn Nizard (M)

Necker-Enfants Malades University Hospital, Department of Pediatric Endocrinology, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Alix 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.

Francesca Peluso (F)

Azienda USL-IRCCS di Reggio Emilia, Medical Genetics Unit, 42123 Reggio Emilia, Italy.

Vincent Pernin (V)

University of Montpellier, Department of Nephrology, Montpellier, France.

Laurence Perrin (L)

Robert Debré University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Christophe 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.

Chitra Prasad (C)

University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.

Madhavi Prasad (M)

University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.

Raissa Relator (R)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.

Marlène 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.

Sophie 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.

Valentin Ruault (V)

Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.

Nathalie Ruiz-Pallares (N)

University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.

Elodie Sanchez (E)

University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.

Debbie Shears (D)

Churchill Hospital, Department of Clinical Genetics, ERN-ITHACA, Oxford, United Kingdom.

Victoria Mok Siu (VM)

University of Western Ontario, London Health Sciences Centre, Department of Pediatrics, London, Ontario, Canada.

Arthur Sorlin (A)

University Hospital of Dijon, Laboratory of Molecular Genetics and Cytogenetics, Inserm UMR 1231 GAD, Dijon, France.

Matthew Tedder (M)

Greenwood Genetic Centre, Greenwod, SC.

Mylène Tharreau (M)

University Hospital of Montpellier, Department of Molecular Genetics and Cytogenomics, Montpellier, France.

Frédéric Tran Mau-Them (FT)

University Hospital of Dijon, Laboratory of Molecular Genetics and Cytogenetics, Inserm UMR 1231 GAD, Dijon, France.

Liselot van der Laan (L)

University of Amsterdam, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, AUMC Department of Human Genetics, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Julien Van Gils (J)

University of Bordeaux, University Hospital of Bordeaux, Department of Medical Genetics, MRGM Inserm UMR1211, F-33000 Bordeaux, France.

Alain Verloes (A)

Robert Debré University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Sandra Whalen (S)

Pitié-Salpêtrière University Hospital, Department of Clinical Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Marjolaine Willems (M)

Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.

Kévin Yauy (K)

Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France.

Roberta Zuntini (R)

Azienda USL-IRCCS di Reggio Emilia, Medical Genetics Unit, 42123 Reggio Emilia, Italy.

Jennifer Kerkhof (J)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.

Bekim Sadikovic (B)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, Londo, ON N6A 5W9, Canada.

David Geneviève (D)

Montpellier University, Inserm UMR1183, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », ERN-ITHACA, Department of Clinical Genetics, University Hospital of Montpellier, Montpellier, France. Electronic address: d-genevieve@chu-montpellier.fr.

Classifications MeSH