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.

中文翻译：

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过度生长综合征的PRC2复杂相关功能障碍：EZH2，EED和SUZ12及其综合征表型的综述。

EZH2，EED和SUZ12基因编码包含多梳抑制复合物2（PRC2）核心成分的蛋白质，该复合物是具有H3K27甲基转移酶活性的表观遗传“书写者”，可催化在组蛋白3的赖氨酸残基27上添加多达三个甲基。 （H3K27）。编码复合物的EZH2和EED亚基的基因中的部分功能丧失变异导致过度生长，大头畸形，骨龄增加，智力残疾和独特的面部特征。由Zeste同系物2（EZH2）增强子内的结构杂合突变引起的EZH2相关过度生长，其表型范围从身材高大，无明显智力障碍或畸形特征到经典的Weaver综合征（OMIM＃277590）。EED相关的过度生长（Cohen-Gibson综合征；OMIM＃617561）由胚胎外胚层发育（EED）中的种系杂合突变引起，并表现出过度生长和智力残疾（OGID），以及与Weaver综合征相似的其他特征。最近，还描述了SUZ12中罕见的编码变体，其表现出的临床特征与之前的两种综合征相似。在这里，我们审查与核心组件EZH2，EED和SUZ12相关的PRC2复杂性和OGID的临床综合征。