Disruption of the histone acetyltransferase MYST4 leads to a noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice

M Kraft; IC Cirstea; AK Voss; T Thomas; I Goehring; BN Sheikh; L Gordon; H Scott; GK Smyth; MR Ahmadian; U Trautmann; M Zenker; M Tartaglia; A Ekici; A Reis; HG Dörr; A Rauch; CT Thiel

Journal article

Disruption of the histone acetyltransferase MYST4 leads to a noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice

M Kraft, IC Cirstea, AK Voss, T Thomas, I Goehring, BN Sheikh, L Gordon, H Scott, GK Smyth, MR Ahmadian, U Trautmann, M Zenker, M Tartaglia, A Ekici, A Reis, HG Dörr, A Rauch, CT Thiel

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2011

DOI: 10.1172/JCI43428

Abstract

Epigenetic regulation of gene expression, through covalent modification of histones, is a key process controlling growth and development. Accordingly, the transcription factors regulating these processes are important targets of genetic diseases. However, surprisingly little is known about the relationship between aberrant epigenetic states, the cellular process affected, and their phenotypic consequences. By chromosomal breakpoint mapping in a patient with a Noonan syndrome-like phenotype that encompassed short stature, blepharoptosis, and attention deficit hyperactivity disorder, we identified haploinsufficiency of the histone acetyltransferase gene MYST histone acetyltransferase (monocyti..

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University of Melbourne Researchers

Tim Thomas Author

Gordon Smyth Author

Grants

Awarded by BMBF network

Awarded by DFG

Awarded by German Ministry of Science and Education [BMBF]

Funding Acknowledgements

We thank the family for giving their consent for this study. This study was supported by the IZKF grant ES to A. Rauch, the BMBF network grant SKELNET (GFGM01141901) to A. Rauch and A. Reis, the DFG grant ZE524/4-1 to M. Zenker, the DFG grant TH896/3-1 to C.T. Thiel, and grants from the F.R.S.-FNRS and the Australian NHMRC. This work was performed as part of our research study addressing the genetics of mental retardation, which was approved by the research ethics committee of the Medical Faculty of the University of Erlangen-Nuremberg. M.R. Ahmadian was supported by the NGFNplus-program of the German Ministry of Science and Education [BMBF, grant 01GS08100] and the Research Committee of the Medical Faculty of the Heinrich-Heine University Dusseldorf.