Details

Autor(en) / Beteiligte

• 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
• Shears, Debbie
• Siu, Victoria Mok
• Sorlin, Arthur
• Tedder, Matthew
• Tharreau, Mylène
• Mau-Them, Frédéric Tran
• van der Laan, Liselot
• Van Gils, Julien
• Verloes, Alain
• Whalen, Sandra
• Willems, Marjolaine
• Yauy, Kévin
• Zuntini, Roberta
• Kerkhof, Jennifer
• Sadikovic, Bekim
• Geneviève, David

Titel

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

Ist Teil von

• Genetics in medicine, 2024-01, Vol.26 (1), p.101007, Article 101007

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 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. 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.