Nature Communications (Sep 2020)
Haploinsufficiency of RREB1 causes a Noonan-like RASopathy via epigenetic reprogramming of RAS-MAPK pathway genes
- Oliver A. Kent,
- Manipa Saha,
- Etienne Coyaud,
- Helen E. Burston,
- Napoleon Law,
- Keith Dadson,
- Sujun Chen,
- Estelle M. Laurent,
- Jonathan St-Germain,
- Ren X. Sun,
- Yoshinori Matsumoto,
- Justin Cowen,
- Aaryn Montgomery-Song,
- Kevin R. Brown,
- Charles Ishak,
- Jose La Rose,
- Daniel D. De Carvalho,
- Housheng Hansen He,
- Brian Raught,
- Filio Billia,
- Peter Kannu,
- Robert Rottapel
Affiliations
- Oliver A. Kent
- Princess Margaret Cancer Centre, University Health Network
- Manipa Saha
- Princess Margaret Cancer Centre, University Health Network
- Etienne Coyaud
- Princess Margaret Cancer Centre, University Health Network
- Helen E. Burston
- Princess Margaret Cancer Centre, University Health Network
- Napoleon Law
- Princess Margaret Cancer Centre, University Health Network
- Keith Dadson
- Toronto General Research Institute
- Sujun Chen
- Princess Margaret Cancer Centre, University Health Network
- Estelle M. Laurent
- Princess Margaret Cancer Centre, University Health Network
- Jonathan St-Germain
- Princess Margaret Cancer Centre, University Health Network
- Ren X. Sun
- Princess Margaret Cancer Centre, University Health Network
- Yoshinori Matsumoto
- Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
- Justin Cowen
- Princess Margaret Cancer Centre, University Health Network
- Aaryn Montgomery-Song
- Princess Margaret Cancer Centre, University Health Network
- Kevin R. Brown
- Princess Margaret Cancer Centre, University Health Network
- Charles Ishak
- Princess Margaret Cancer Centre, University Health Network
- Jose La Rose
- Princess Margaret Cancer Centre, University Health Network
- Daniel D. De Carvalho
- Princess Margaret Cancer Centre, University Health Network
- Housheng Hansen He
- Princess Margaret Cancer Centre, University Health Network
- Brian Raught
- Princess Margaret Cancer Centre, University Health Network
- Filio Billia
- Toronto General Research Institute
- Peter Kannu
- Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children
- Robert Rottapel
- Princess Margaret Cancer Centre, University Health Network
- DOI
- https://doi.org/10.1038/s41467-020-18483-9
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 12
Abstract
Mutations in RAS-MAPK pathway genes are implicated in Noonan-spectrum, yet up to 20% of cases have unknown cause. Here, the authors identify RREB1 underlying a 6p microdeletion RASopathy-like syndrome and show that RREB1, SIN3A and KDM1A form a transcriptional repressive complex to control methylation of MAPK pathway genes.
