Title :

Clinical and functional heterogeneity associated with the disruption of Retinoic Acid Receptor beta

Author(s) :

Caron, Véronique [Auteur]
Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]
Chassaing, Nicolas [Auteur]
Service Génétique Médicale [CHU Toulouse]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
Ragge, Nicola [Auteur]
Birmingham Women's and Children's NHS Foundation Trust
Oxford Brookes University
Boschann, Felix [Auteur]
Charité - UniversitätsMedizin = Berlin University Medicine
My-Hoa Ngu, Angelina [Auteur]
Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]
Chorfi, Sarah [Auteur]
Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]
Lakhani, Saquib A. [Auteur]
Yale University [New Haven]
Ji, Weizhen [Auteur]
Yale University [New Haven]
Steiner, Laurie [Auteur]
University of Rochester Medical Center [URMC]
Marcadier, Julien [Auteur]
Jansen, Philip R. [Auteur]
Amsterdam University Medical Centers [Amsterdam UMC]
Van De Pol, Laura A. [Auteur]
Amsterdam University Medical Centers [Amsterdam UMC]
Van Hagen, Johanna M. [Auteur]
Amsterdam University Medical Centers [Amsterdam UMC]
Russi, Alvaro Serrano [Auteur]
Children’s Hospital Los Angeles [Los Angeles]
Le Guyader, Gwenaël [Auteur]
Service de Génétique Médicale [CHU Poitiers]
Nordenskjöld, Magnus [Auteur]
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Nordgren, Ann [Auteur]
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Anderlid, Britt-Marie [Auteur]
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Plaisancié, Julie [Auteur]
Service Génétique Médicale [CHU Toulouse]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
Stoltenburg, Corinna [Auteur]
Charité - UniversitätsMedizin = Berlin University Medicine
Horn, Denise [Auteur]
Charité - UniversitätsMedizin = Berlin University Medicine
Drenckhahn, Anne [Auteur]
Charité - UniversitätsMedizin = Berlin University Medicine
Hamdan, Fadi F. [Auteur]
Université de Montréal [UdeM]
CHU Sainte Justine [Montréal]
Lefebvre, Mathilde [Auteur]
Hôpital Robert Debré Paris
Attie-Bitach, Tania [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Forey, Peggy [Auteur]
Centre Hospitalier d'Angoulême [CH Angoulême]
Smirnov, Vasily [Auteur]
Service d’Exploration de la Vision et Neuro-ophtalmologie [CHU Lille]
Ernould, Françoise [Auteur]
Hôpital Claude Huriez [Lille]
Jacquemont, Marie-Line [Auteur]
Centre Hospitalier Universitaire de La Réunion [CHU La Réunion]
Grotto, Sarah [Auteur]
Hôpital Robert Debré Paris
Alcantud, Alberto [Auteur]
Coret, Alicia [Auteur]
Ferrer-Avargues, Rosario [Auteur]
Srivastava, Siddharth [Auteur]
Boston Children's Hospital
Vincent, Catherine [Auteur]
Hôpital Jeanne de Flandre [Lille]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Romoser, Shelby [Auteur]
University of Iowa [Iowa City]
Safina, Nicole [Auteur]
University of Iowa [Iowa City]
Saade, Dimah [Auteur]
Carver College of Medicine, University of Iowa
Lupski, James R. [Auteur]
Baylor College of Medicine [BCM]
Texas Children's Hospital [Houston, USA]
Calame, Daniel G. [Auteur]
Baylor College of Medicine [BCM]
Texas Children's Hospital [Houston, USA]
Geneviève, David [Auteur]
Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
Chatron, Nicolas [Auteur]
Hospices Civils de Lyon [HCL]
Institut NeuroMyoGène - Appui à la recherche [INMG-AR]
Schluth-Bolard, Caroline [Auteur]
Hospices Civils de Lyon [HCL]
Myers, Kenneth A. [Auteur]
McGill University = Université McGill [Montréal, Canada]
Dobyns, William B. [Auteur]
University of Minnesota System [UMN]
Calvas, Patrick [Auteur]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
Service Génétique Médicale [CHU Toulouse]
Salmon, Caroline [Auteur]
Royal Surrey County Hospital [NHS Royal Surrey]
Holt, Richard [Auteur]
Oxford Brookes University
Elmslie, Frances [Auteur]
St George’s University Hospitals
Allaire, Marc [Auteur]
Lawrence Berkeley National Laboratory [Berkeley] [LBNL]
Prigozhin, Daniil M. [Auteur]
Lawrence Berkeley National Laboratory [Berkeley] [LBNL]
Tremblay, André [Auteur]
Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]
Michaud, Jacques L. [Auteur]
Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]

Journal title :

Genetics in Medicine

Abbreviated title :

Genet Med

Volume number :

25

Pages :

100856

Publisher :

Nature Publishing Group

Publication date :

2023-04-20

ISSN :

1530-0366

English keyword(s) :

Dystonia
Global developmental delay
Microphthalmia
Retinoic acid
Retinoic acid receptor beta

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Purpose Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with ...
Show more >Purpose Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12. Methods We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids. Results We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators’ recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment. Conclusion Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Cohorte nationale maladies rares

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2024-06-25T21:30:26Z
2024-10-03T13:07:23Z