The Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2-related overgrowth) and Cohen-Gibson syndrome (EED-related overgrowth). Imagawa et al. (2017) initially reported a singleton female with a Weaver-like phenotype with a rare coding SUZ12 variant-the same group subsequently reported two additional affected patients. Here we describe a further 10 patients (from nine families) with rare heterozygous SUZ12 variants who present with a Weaver-like phenotype. We report four frameshift, two missense, one nonsense, and two splice site variants. The affected patients demonstrate variable pre- and postnatal overgrowth, dysmorphic features, musculoskeletal abnormalities and developmental delay/intellectual disability. Some patients have genitourinary and structural brain abnormalities, and there may be an association with respiratory issues. The addition of these 10 patients makes a compelling argument that rare pathogenic SUZ12 variants frequently cause overgrowth, physical abnormalities, and abnormal neurodevelopmental outcomes in the heterozygous state. Pathogenic SUZ12 variants may be de novo or inherited, and are sometimes inherited from a mildly-affected parent. Larger samples sizes will be needed to elucidate whether one or more clinically-recognizable syndromes emerge from different variant subtypes.

中文翻译：

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罕见的SUZ12变体通常会导致过度生长的表型。

Polycomb阻抑复合物2是表观遗传的编写者和募集者，在转录沉默中起作用。已经发现其组成蛋白中的构成致病性变体会导致两种已确立的过度生长综合征：Weaver综合征（EZH2相关过度生长）和Cohen-Gibson综合征（EED相关过度生长）。今川等。（2017）最初报道了一名具有Weaver样表型的单身女性，其罕见的SUZ12变异编码-同一组随后报告了另外两名受影响的患者。在这里，我们描述了另外10名患者（来自9个家庭）具有罕见的杂合SUZ12变异体的患者，这些变异体表现为Weaver样表型。我们报告了四个移码，两个错义，一个废话和两个拼接位点变体。受影响的患者表现出出生前和出生后的过度生长，畸形特征，肌肉骨骼异常和发育延迟/智力障碍。一些患者的泌尿生殖系统和结构性脑部异常，可能与呼吸系统疾病有关。这10名患者的加入令人信服地提出，罕见的病原体SUZ12变异体经常在杂合状态下导致过度生长，身体异常和异常的神经发育结果。致病性SUZ12变异可能是新生的，也可能是遗传的，有时是从轻微受影响的父母那里遗传的。需要更大的样本量以阐明一种或多种临床上可识别的综合征是否来自不同的变异亚型。可能与呼吸系统疾病有关。这10名患者的加入令人信服地提出，罕见的病原体SUZ12变异体经常在杂合状态下导致过度生长，身体异常和异常的神经发育结果。致病性SUZ12变异可能是新生的，也可能是遗传的，有时是从轻微受影响的父母那里遗传的。需要更大的样本量以阐明一种或多种临床上可识别的综合征是否来自不同的变异亚型。可能与呼吸系统疾病有关。这10名患者的加入令人信服地提出，罕见的病原体SUZ12变异体经常在杂合状态下导致过度生长，身体异常和异常的神经发育结果。致病性SUZ12变异可能是新生的，也可能是遗传的，有时是从轻微受影响的父母那里遗传的。需要更大的样本量以阐明一种或多种临床上可识别的综合征是否来自不同的变异亚型。并且有时是从一个轻度受影响的父母那里继承的。需要更大的样本量以阐明一种或多种临床上可识别的综合征是否来自不同的变异亚型。并且有时是从一个轻度受影响的父母那里继承的。需要更大的样本量以阐明一种或多种临床上可识别的综合征是否来自不同的变异亚型。