Signal sequence receptor protein 4 (SSR4) is a subunit of the translocon‐associated protein complex, which participates in the translocation of proteins across the endoplasmic reticulum membrane, enhancing the efficiency of N‐linked glycosylation. Pathogenic variants in SSR4 cause a congenital disorder of glycosylation: SSR4–congenital disorders of glycosylation (CDG). We describe three SSR4–CDG boys and review the previously reported. All subjects presented with hypotonia, failure to thrive, developmental delay, and dysmorphic traits and showed a type 1 serum sialotransferrin profile, facilitating the diagnosis. Genetic confirmation of this X‐linked CDG revealed one de novo hemizygous deletion, one maternally inherited deletion, and one de novo nonsense mutation of SSR4. The present subjects highlight the similarities with a connective tissue disorder (redundant skin, joint laxity, blue sclerae, and vascular tortuosity). The connective tissue problems are relevant, and require preventive rehabilitation measures. As an X‐linked disorder, genetic counseling is essential.

中文翻译：

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扩展 X 连锁 SSR4-CDG 的表型：结缔组织的意义

信号序列受体蛋白 4 (SSR4) 是易位子相关蛋白复合物的一个亚基，它参与蛋白质跨内质网膜的转运，提高 N 连接糖基化的效率。SSR4中的致病性变异导致先天性糖基化障碍：SSR4-先天性糖基化障碍 (CDG)。我们描述了三个 SSR4-CDG 男孩并回顾了之前报道的。所有受试者均出现肌张力减退、发育迟缓、发育迟缓和畸形特征，并显示 1 型血清唾液酸转铁蛋白谱，有助于诊断。该 X 连锁 CDG 的遗传确认揭示了SSR4的一个从头半合子缺失、一个母系遗传缺失和一个从头无义突变. 目前的主题强调了与结缔组织疾病（多余的皮肤、关节松弛、蓝色巩膜和血管曲折）的相似之处。结缔组织问题是相关的，需要预防性康复措施。作为 X 连锁疾病，遗传咨询是必不可少的。