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Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features
- Source :
- American Journal of Human Genetics, 103(5), 786-793. CELL PRESS, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, American Journal of Human Genetics, 103, 786-793, American Journal of Human Genetics, 103, 5, pp. 786-793
- Publication Year :
- 2018
-
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, 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.
- Subjects :
- 0301 basic medicine
EXPRESSION
PCGF2
Polycomb Group Ring Finger 2
MEL-18
Mutant
dysmorphism
PROTEIN
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
0302 clinical medicine
Report
Histone H2A
Genetics
Gene silencing
Missense mutation
polymicrogyria
Craniofacial
SPECIFICATION
Gene
MEL18
intellectual disability
Genetics (clinical)
CYCLIN D2
UBIQUITYLATION
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
biology
REPRESSION
Correction
Phenotype
GENE
030104 developmental biology
Histone
030220 oncology & carcinogenesis
biology.protein
HISTONE H2A
STEM-CELLS
Subjects
Details
- ISSN :
- 00029297
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- American Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....b42653bf0678df6d6b3a18f4c5e210bd