Expanding the phenotype of X-linked SSR4-CDG: Connective tissue implications.

Human mutation 2021 Feb

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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. © 2020 Wiley Periodicals LLC.

Citation

Claudia Castiglioni, François Feillet, Christine Barnerias, Arnaud Wiedemann, Jordi Muchart, Fanny Cortes, Cristina Hernando-Davalillo, Raquel Montero, Thierry Dupré, Arnaud Bruneel, Nathalie Seta, Sandrine Vuillaumier-Barrot, Mercedes Serrano. Expanding the phenotype of X-linked SSR4-CDG: Connective tissue implications. Human mutation. 2021 Feb;42(2):142-149