In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. EMC10 is a bone marrow‐derived angiogenic growth factor that plays an important role in infarct vascularization and promoting tissue repair. However, this gene has not been previously associated with human disease. Herein, we describe a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole‐exome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real‐time PCR (RT‐qPCR)‐based expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. For the first time in the literature, the EMC10 gene variant was associated with mild ID, speech delay, and GDD. Thus, this gene plays a key role in developmental milestones, with the potential to cause neurodevelopmental disorders in humans.

中文翻译：

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在具有全面发育迟缓、轻度智力障碍和言语迟缓的家族中鉴定出 EMC10 纯合变异。

近年来，一些基因与全球发育迟缓 (GDD) 和智力障碍 (ID) 的可变疾病表现有关。已知内质网膜蛋白复合物 (EMC) 家族参与 GDD 和 ID。EMC1 的纯合变体与 GDD、脊柱侧弯和小脑萎缩有关，表明该途径与神经遗传性疾病的相关性。EMC10 是一种骨髓来源的血管生成生长因子，在梗塞血管化和促进组织修复中起重要作用。然而，该基因以前与人类疾病无关。在这里，我们描述了一个沙特家庭，其中有两个人隔离了隐性神经发育障碍。两个受影响的人都表现出轻微的 ID、语言延迟和 GDD。进行全外显子组测序（WES）和 Sanger 测序以鉴定候选基因。此外，为了阐明变体的功能影响，进行了基于定量实时 PCR (RT-qPCR) 的表达分析。WES 揭示了一个纯合剪接受体位点变体 (c.679-1G>A)EMC10（染色体19q13.33）在家族内完全分离。RT-qPCR 显示患者的相对EMC10基因表达显着降低，表明所鉴定变异的致病性。在文献中，EMC10基因变异首次与轻度 ID、语言延迟和 GDD 相关。因此，该基因在发育里程碑中起着关键作用，有可能导致人类神经发育障碍。