PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes

Sharri Cyrus, Deepika Burkardt, David D. Weaver, William T. Gibson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The EZH2, EED, and SUZ12 genes encode proteins that comprise core components of the polycomb repressive complex 2 (PRC2), an epigenetic “writer” with H3K27 methyltransferase activity, catalyzing the addition of up to three methyl groups on histone 3 at lysine residue 27 (H3K27). Partial loss-of-function variants in genes encoding the EZH2 and EED subunits of the complex lead to overgrowth, macrocephaly, advanced bone age, variable intellectual disability, and distinctive facial features. EZH2-associated overgrowth, caused by constitutional heterozygous mutations within Enhancer of Zeste homologue 2 (EZH2), has a phenotypic spectrum ranging from tall stature without obvious intellectual disability or dysmorphic features to classical Weaver syndrome (OMIM #277590). EED-associated overgrowth (Cohen–Gibson syndrome; OMIM #617561) is caused by germline heterozygous mutations in Embryonic Ectoderm Development (EED), and manifests overgrowth and intellectual disability (OGID), along with other features similar to Weaver syndrome. Most recently, rare coding variants in SUZ12 have also been described that present with clinical characteristics similar to the previous two syndromes. Here we review the PRC2 complex and clinical syndromes of OGID associated with core components EZH2, EED, and SUZ12.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Polycomb Repressive Complex 2
Ectoderm
Embryonic Development
Intellectual Disability
Phenotype
Genetic Databases
Megalencephaly
Germ-Line Mutation
Methyltransferases
Epigenomics
Histones
Lysine
Enhancer of Zeste Homolog 2 Protein
Bone and Bones
Mutation
Genes

Keywords

  • Cohen–Gibson syndrome
  • overgrowth
  • polycomb repressive complex 2
  • SUZ12-related overgrowth
  • Weaver syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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title = "PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes",
abstract = "The EZH2, EED, and SUZ12 genes encode proteins that comprise core components of the polycomb repressive complex 2 (PRC2), an epigenetic “writer” with H3K27 methyltransferase activity, catalyzing the addition of up to three methyl groups on histone 3 at lysine residue 27 (H3K27). Partial loss-of-function variants in genes encoding the EZH2 and EED subunits of the complex lead to overgrowth, macrocephaly, advanced bone age, variable intellectual disability, and distinctive facial features. EZH2-associated overgrowth, caused by constitutional heterozygous mutations within Enhancer of Zeste homologue 2 (EZH2), has a phenotypic spectrum ranging from tall stature without obvious intellectual disability or dysmorphic features to classical Weaver syndrome (OMIM #277590). EED-associated overgrowth (Cohen–Gibson syndrome; OMIM #617561) is caused by germline heterozygous mutations in Embryonic Ectoderm Development (EED), and manifests overgrowth and intellectual disability (OGID), along with other features similar to Weaver syndrome. Most recently, rare coding variants in SUZ12 have also been described that present with clinical characteristics similar to the previous two syndromes. Here we review the PRC2 complex and clinical syndromes of OGID associated with core components EZH2, EED, and SUZ12.",
keywords = "Cohen–Gibson syndrome, overgrowth, polycomb repressive complex 2, SUZ12-related overgrowth, Weaver syndrome",
author = "Sharri Cyrus and Deepika Burkardt and Weaver, {David D.} and Gibson, {William T.}",
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AU - Cyrus, Sharri

AU - Burkardt, Deepika

AU - Weaver, David D.

AU - Gibson, William T.

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