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

Hum Mutat. 2021 Feb;42(2):142-149. doi: 10.1002/humu.24151. Epub 2020 Dec 21.

Abstract

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.

Keywords: SSR4; TRAP complex; congenital disorders of glycosylation; connective tissue disorders; translocon associated complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins* / genetics
  • Congenital Disorders of Glycosylation* / diagnosis
  • Congenital Disorders of Glycosylation* / genetics
  • Congenital Disorders of Glycosylation* / pathology
  • Connective Tissue / pathology
  • Glycosylation
  • Humans
  • Male
  • Membrane Glycoproteins* / genetics
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear* / genetics
  • Receptors, Peptide* / genetics

Substances

  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Peptide
  • signal sequence receptor