Expanding the Molecular and Clinical Phenotype of SSR4-CDG.

Abstract

Congenital disorders of glycosylation (CDG) are a group of mostly autosomal recessive disorders primarily characterized by neurological abnormalities. Recently, we described a single CDG patient with a de novo mutation in the X-linked gene, Signal Sequence Receptor 4 (SSR4). We performed whole-exome sequencing to identify causal variants in several affected individuals who had either an undifferentiated neurological disorder or unsolved CDG of unknown etiology based on abnormal transferrin glycosylation. We now report eight affected males with either de novo (4) or inherited (4) loss of function mutations in SSR4. Western blot analysis revealed that the mutations caused a complete loss of SSR4 protein. In nearly all cases, the abnormal glycosylation of serum transferrin was only slightly above the accepted normal cutoff range.

• Authors: Bobby G Ng, Kimiyo Raymond, Martin Kircher, Kati J Buckingham, Tim Wood, Jay Shendure, Deborah A Nickerson, Michael J Bamshad, University of Washington Center for Mendelian Genomics, Jonathan T S Wong, Fabiola Paoli Monteiro, Brett H Graham, Sheryl Jackson, Rebecca Sparkes, Angela E Scheuerle, Sara Cathey, Fernando Kok, James B Gibson, Hudson H Freeze
• Journal: Human mutation (Hum Mutat) Vol. 36 Issue 11 Pg. 1048-51 (Nov 2015) ISSN: 1098-1004 [Electronic] United States
• PMID: 26264460 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2015 WILEY PERIODICALS, INC.

Chemical References

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

Topics

• Calcium-Binding Proteins (genetics)
• Congenital Disorders of Glycosylation (diagnosis, genetics)
• DNA Mutational Analysis
• Exome
• Gene Order
• Genes, X-Linked
• Genetic Loci
• Humans
• Male
• Membrane Glycoproteins (genetics)
• Mutation
• Phenotype
• Receptors, Cytoplasmic and Nuclear (genetics)
• Receptors, Peptide (genetics)