Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features (CROSBI ID 271340)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Turnpenny, Peter D. ; Wright, Michael J. ; Sloman, Melissa ; Caswell, Richard ; van Essen, Anthony J. ; Gerkes, Erica ; Pfundt, Rolph ; White, Susan M. ; Shaul-Lotan, Nava ; Carpenter, Lori ; Schaefer, G. Bradley ; Fryer, Alan ; Innes, A. Micheil ; Forbes, Kirsten P. ; Chung, Wendy K. ; McLaughlin, Heather ; Henderson, Lindsay B. ; Roberts, Amy E. ; Heath, Karen E. ; Paumard-Hernández, Beatriz ; Gener, Blanca ; Fawcett, Katherine A. ; Gjergja-Juraški, Romana ; Pilz, Daniela T. ; Fry, Andrew E.
engleski
Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features
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, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Computer structural modeling suggests the substitutions alter an N-terminal loop of PCGF2 critical for histone biding. Mutant PCGF2 may have dominant-negative effects, sequestering PRC1 components into complexes that lack the ability to interact efficiently with histones. These findings demonstrate the important role of PCGF2 in human development and confirm that heterozygous substitutions of the Pro65 residue of PCGF2 cause a recognizable syndrome characterized by distinctive craniofacial, neurological, cardiovascular, and skeletal features.
PCGF2 ; Polycomb Group Ring Finger 2 ; MEL18 ; intellectual disability ; dysmorphism ; polymicrogyria
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
Podaci o izdanju
103 (5)
2018.
786-793
objavljeno
0002-9297
1537-6605
10.1016/j.ajhg.2018.09.012
Povezanost rada
Temeljne medicinske znanosti