In this report, we describe two cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Genome sequencing failed to identify variants in known disease‐associated genes explaining the phenotype. Extended comprehensive analysis of the two affected cousins' genomes, however, revealed that both share the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The potential vital biological role of VPS26C, the nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals all support that VPS26C is a novel gene associated with a previously unrecognized syndrome characterized by neurodevelopmental deficits, growth failure, skeletal abnormalities, and distinctive facial features.

中文翻译：

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两个堂兄的VPS26C纯合性无意义变体，具有神经发育缺陷，生长衰竭，骨骼异常和独特的面部特征

在这份报告中，我们描述了两个表亲，它们具有认知障碍，生长衰竭，骨骼异常和独特的面部特征。基因组测序未能鉴定出与疾病相关的已知基因的表型。扩展的两个受影响的表兄弟基因组的全面分析，但是，揭示了两者的份额在纯合废话变种c.178G> T（p.Glu60 *）VPS26C基因。该基因编码VPS26C，它是猎犬整体膜蛋白回收途径的成员。VPS26C的潜在重要生物学作用，变体的性质（预计会导致功能丧失），表达研究表明突变体转录物显着减少，纯合变体与表型在两种受影响的情况下共分离每个人都支持VPS26C是一种与先前无法识别的综合征相关的新基因，该综合征的特征是神经发育缺陷，生长衰竭，骨骼异常和独特的面部特征。