Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features

Peter D Turnpenny; Michael J Wright; Melissa Sloman; Richard Caswell; Anthony J van Essen; Erica Gerkes; Rolph Pfundt; Susan M White; Nava Shaul-Lotan; Lori Carpenter; G Bradley Schaefer; Alan Fryer; A Micheil Innes; Kirsten P Forbes; Wendy K Chung; Heather McLaughlin; Lindsay B Henderson; Amy E Roberts; Karen E Heath; Beatriz Paumard-Hernandez; Blanca Gener; Katherine A Fawcett; Romana Gjergja-Juraski; Daniela T Pilz; Andrew E Fry

Journal article

Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features

Peter D Turnpenny, Michael J Wright, Melissa Sloman, Richard Caswell, Anthony J van Essen, Erica Gerkes, Rolph Pfundt, Susan M White, Nava Shaul-Lotan, Lori Carpenter, G Bradley Schaefer, Alan Fryer, A Micheil Innes, Kirsten P Forbes, Wendy K Chung, Heather McLaughlin, Lindsay B Henderson, Amy E Roberts, Karen E Heath, Beatriz Paumard-Hernandez Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2018

DOI: 10.1016/j.ajhg.2018.09.012

Abstract

PCGF2 encodes the polycomb group ring finger 2 protein, a transcriptional repressor involved in cell proliferation, differentiation, and embryogenesis. PCGF2 is a component of the polycomb repressive complex 1 (PRC1), a multiprotein complex which controls gene silencing through histone modification and chromatin remodelling. We report the phenotypic characterization of 13 patients (11 unrelated individuals and a pair of monozygotic twins) with missense mutations in PCGF2. All the mutations affected the same highly conserved proline in PCGF2 and were de novo, excepting maternal mosaicism in one. The patients demonstrated a recognizable facial gestalt, intellectual disability, feeding problems..

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University of Melbourne Researchers

Susan White Author Paediatrics Royal Children's Hospital

Grants

Awarded by Academy of Medical Sciences

Awarded by MINECO

Awarded by Health Innovation Challenge Fund

Awarded by Wellcome Trust Sanger Institute

Funding Acknowledgements

A.E.F. was supported by the Academy of Medical Sciences (grant: AMS-SGCL8-Fry). This work was also supported by the Wales Epilepsy Research Network and the Wales Gene Park. W.K.C. received support from the Simons Foundation and JPB Foundation. K.E.H. received support from MINECO (grants: SAF2015-66831-R, SAF2017-84646-R). The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between theWellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of the funding agencies.