Castiglioni Claudia, Feillet François, Barnerias Christine, Wiedemann Arnaud, Muchart Jordi, Cortes Fanny, Hernando-Davalillo Cristina, Montero Raquel, Dupré Thierry, Bruneel Arnaud, Seta Nathalie, Vuillaumier-Barrot Sandrine, Serrano Mercedes
Department of Pediatric Neurology, Rare Disease Center, Clínica Las Condes, Santiago, Chile.
Department of Pediatrics, Reference Center for Inborn Errors of Metabolism, University Hospital of Nancy, Nancy, France.
Hum Mutat. 2021 Feb;42(2):142-149. doi: 10.1002/humu.24151. Epub 2020 Dec 21.
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.
信号序列受体蛋白4（SSR4）是转位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位过程，提高N-糖基化的效率。SSR4中的致病变异会导致糖基化先天性疾病：SSR4-糖基化先天性疾病（CDG）。我们描述了三名患有SSR4-CDG的男孩，并对先前报道的病例进行了回顾。所有受试者均表现为肌张力减退、生长发育迟缓、发育延迟和畸形特征，并呈现1型血清唾液酸转铁蛋白谱，有助于诊断。这种X连锁CDG的基因确认显示，有一例新发半合子缺失、一例母系遗传缺失和一例SSR4的新发无义突变。目前的这些受试者突出了与一种结缔组织疾病（皮肤冗余、关节松弛、巩膜蓝染和血管迂曲）的相似性。结缔组织问题很重要，需要采取预防性康复措施。作为一种X连锁疾病，遗传咨询至关重要。
