Premium
Congenital disorder of glycosylation caused by a mutation in SSR4 , the signal sequence receptor 4 protein of the TRAP complex (789.3)
Author(s) -
Losfeld MarieEstelle,
Ng Bobby,
Kircher Martin,
Buckingham Kati,
Turner Emily,
Eroshkin Alexey,
Smith Joshua,
Shendure Jay,
Nickerson Deborah,
Bamshad Michael,
Freeze Hudson
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.789.3
Subject(s) - glycosylation , gene , exon , glycoprotein , mutation , biology , n linked glycosylation , exome sequencing , genetics , microbiology and biotechnology , glycan
Congenital Disorders of Glycosylation (CDG) are a family of genetic disorders affecting the glycosylation pathway or the trafficking of glycoproteins. Nearly 50 genes causing CDG have been described, but many patients biochemically diagnosed with CDG do not have mutations in known genes. Among our CDG patients, we identified by exome saequencing, in three patients, new variants of the X‐linked SSR4 gene which encodes a protein of the heterotetrameric translocon‐associated protein (TRAP) complex. Two of these variants results in the absence of SSR4 expression. In these cases, we observed that expression of other TRAP complex proteins was also reduced. The glycosylation marker Glyc‐ER‐GFP was used to confirm the underglycosylation in fibroblasts from patients. Over‐expression of the wild type SSR4 allele partially restores glycosylation of the marker and expression of the other members of the TRAP complex. This is the first evidence that the TRAP complex, which binds to the oligosaccharyltransferase complex, is directly involved in N‐glycosylation. Grant Funding Source : Supported by the National Institutes of Health grant [R01DK55615] and “The Rocket Fund”.