Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioural abnormalities and seizures. Only 11 affected individuals have been reported to-date, and the phenotype associated with pathogenic variants in this gene have not been fully defined. Here, we present 16 additional patients with predicted pathogenic heterozygous variants in ZMYND11, including four individuals from the same family, to further delineate and expand the genotypic and phenotypic spectrum of ZMYND11-related syndromic intellectual disability. The associated phenotype includes developmental delay, particularly affecting speech, mild-moderate intellectual disability, significant behavioural abnormalities, seizures, and hypotonia. There are subtle shared dysmorphic features, including prominent eyelashes and eyebrows, depressed nasal bridge with bulbous nasal tip, anteverted nares, thin vermilion of the upper lip and wide mouth. Novel features include brachydactyly and tooth enamel hypoplasia. Most identified variants are likely to result in premature truncation and/or nonsense mediated decay. Two ZMYND11 variants located in the final exon - p.(Gln586*) (likely escaping nonsense-mediated decay) and p.(Cys574Arg) - are predicted to disrupt the MYND-type zinc finger motif and likely interfere with binding to its interaction partners. Hence, the homogeneous phenotype likely results from a common mechanism of loss-of-function. This article is protected by copyright. All rights reserved.

中文翻译：

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ZMYND11相关的综合征性智力障碍：16例患者描述并扩展了表型谱。

ZMYND11中的病原体变异体，其作为转录抑制因子，与智力残疾，行为异常和癫痫发作有关。迄今仅报道了11个受影响的个体，并且与该基因中的致病变体有关的表型尚未完全确定。在这里，我们介绍了16名ZMYND11病原体杂合变异性预测的患者，包括来自同一家族的4个人，以进一步描述和扩大ZMYND11相关综合征智力障碍的基因型和表型谱。相关的表型包括发育迟缓，特别是影响言语，轻度中度智力障碍，重大的行为异常，癫痫发作和肌张力低下。有一些细微的共同畸变特征，包括突出的睫毛和眉毛，鼻梁凹陷，鼻端呈球形，弯曲的鼻孔，上唇的朱红色细唇和宽阔的嘴巴。新颖的功能包括近距离接触和牙釉质发育不全。大多数鉴定出的变异可能导致过早的截短和/或无意义的介导的衰变。最终外显子中的两个ZMYND11变体-p。（Gln586 *）（可能逃避无义介导的衰变）和p。（Cys574Arg）-预计会破坏MYND型锌指基序并可能干扰与其相互作用伴侣的结合。因此，同质表型可能是由功能丧失的共同机制引起的。本文受版权保护。版权所有。新颖的功能包括近距离接触和牙釉质发育不全。大多数鉴定出的变异可能导致过早的截短和/或无意义的介导的衰变。最终外显子中的两个ZMYND11变体-p。（Gln586 *）（可能逃避无义介导的衰变）和p。（Cys574Arg）-预计会破坏MYND型锌指基序并可能干扰与其相互作用伴侣的结合。因此，同质表型可能是由功能丧失的共同机制引起的。本文受版权保护。版权所有。新颖的功能包括近距离接触和牙釉质发育不全。大多数鉴定出的变异可能导致过早的截短和/或无意义的介导的衰变。最终外显子中的两个ZMYND11变体-p。（Gln586 *）（可能逃避无义介导的衰变）和p。（Cys574Arg）-预计会破坏MYND型锌指基序并可能干扰与其相互作用伴侣的结合。因此，同质表型可能是由功能丧失的共同机制引起的。本文受版权保护。版权所有。（Cys574Arg）-预计会破坏MYND型锌指基序，并可能干扰与其相互作用伴侣的结合。因此，同质表型可能是由功能丧失的共同机制引起的。本文受版权保护。版权所有。（Cys574Arg）-预计会破坏MYND型锌指基序，并可能干扰与其相互作用伴侣的结合。因此，同质表型可能是由功能丧失的共同机制引起的。本文受版权保护。版权所有。