Hunter Genetics, Waratah, New South Wales, Australia.
University of Newcastle, Callaghan, New South Wales, Australia.
Am J Med Genet A. 2024 Feb;194(2):374-382. doi: 10.1002/ajmg.a.63438. Epub 2023 Oct 16.
EED is a core component of polycomb repressive complex 2 (PRC2) with EZH2 and SUZ12. PRC2 has H3K27 methyltransferase activity (HMTase) that catalyzes the addition of up to three methyl groups on histone 3 at lysine residue 27 (H3K27). Germline heterozygous variants in EED, SUZ12, and EZH2 have been identified in patients with overgrowth and multiple dysmorphic features. The clinical manifestations of these syndromes significantly overlap: generalized overgrowth, intellectual disability, and scoliosis. To date, 11 unrelated patients have been published with missense variants in EED at highly conserved amino acids. We report three affected members in a family with a previously reported missense variant. All three affected members manifested very similarly, and this represents a homogenous clinical phenotype associated with EED related intellectual disability and overgrowth. This disorder is appropriately called Cohen-Gibson syndrome.
EED 是多梳抑制复合物 2(PRC2)的核心组成部分,与 EZH2 和 SUZ12 一起。PRC2 具有组蛋白 3 赖氨酸 27(H3K27)上多达三个甲基的组蛋白 3 添加的 H3K27 甲基转移酶活性(HMTase)。EED、SUZ12 和 EZH2 的种系杂合变异已在过度生长和多种发育不良特征的患者中被发现。这些综合征的临床表现显著重叠:全身性过度生长、智力残疾和脊柱侧凸。迄今为止,已有 11 名无关患者在 EED 高度保守的氨基酸中发表了错义变异。我们报告了一个家族中的三个受影响的成员,该家族中存在先前报道的错义变异。所有三个受影响的成员表现非常相似,这代表了与 EED 相关的智力残疾和过度生长相关的同质临床表型。这种疾病被恰当地称为 Cohen-Gibson 综合征。