Nature Communications (Apr 2021)
Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans
- Angelica Gualtieri,
- Nikolina Kyprianou,
- Louise C. Gregory,
- Maria Lillina Vignola,
- James G. Nicholson,
- Rachael Tan,
- Shin-ichi Inoue,
- Valeria Scagliotti,
- Pedro Casado,
- James Blackburn,
- Fernando Abollo-Jimenez,
- Eugenia Marinelli,
- Rachael E. J. Besser,
- Wolfgang Högler,
- I. Karen Temple,
- Justin H. Davies,
- Andrey Gagunashvili,
- Iain C.A.F. Robinson,
- Sally A. Camper,
- Shannon W. Davis,
- Pedro R. Cutillas,
- Evelien F. Gevers,
- Yoko Aoki,
- Mehul T. Dattani,
- Carles Gaston-Massuet
Affiliations
- Angelica Gualtieri
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Nikolina Kyprianou
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Louise C. Gregory
- Genetics and Genomic Medicine Research and Teaching Department, UCL, Great Ormond Street Institute of Child Health
- Maria Lillina Vignola
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- James G. Nicholson
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Rachael Tan
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Shin-ichi Inoue
- Department of Medical Genetics, Tohoku University School of Medicine
- Valeria Scagliotti
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Pedro Casado
- Integrative Cell Signalling and Proteomics, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London
- James Blackburn
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Fernando Abollo-Jimenez
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Eugenia Marinelli
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Rachael E. J. Besser
- Genetics and Genomic Medicine Research and Teaching Department, UCL, Great Ormond Street Institute of Child Health
- Wolfgang Högler
- Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz
- I. Karen Temple
- Faculty of Medicine, University of Southampton
- Justin H. Davies
- Child Health Directorate, University of Southampton
- Andrey Gagunashvili
- NIHR Biomedical Research Centre, Great Ormond Street Hospital, Children NHS Foundation Trust and UCL
- Iain C.A.F. Robinson
- The Francis Crick Institute
- Sally A. Camper
- Department of Human Genetics, University of Michigan
- Shannon W. Davis
- Department of Biological Sciences, University of South Carolina
- Pedro R. Cutillas
- Integrative Cell Signalling and Proteomics, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London
- Evelien F. Gevers
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- Yoko Aoki
- Department of Medical Genetics, Tohoku University School of Medicine
- Mehul T. Dattani
- Genetics and Genomic Medicine Research and Teaching Department, UCL, Great Ormond Street Institute of Child Health
- Carles Gaston-Massuet
- Centre for Endocrinology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London
- DOI
- https://doi.org/10.1038/s41467-021-21712-4
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 18
Abstract
Mutations in components of the MAP kinase pathway are associated with a group of syndromes known as RASopathies. Here, the authors identify gain-of-function mutations in BRAF in patients with RASopathies and congenital hypopituitarisms. This article demonstrates a central role for BRAF in the development of the hypothalamo-pituitary axis leading to endocrine deficiencies in patients with RASopathies.
