Expanding the Molecular and Clinical Phenotype of SSR4-CDG - PubMed (original) (raw)

Case Reports

. 2015 Nov;36(11):1048-51.

doi: 10.1002/humu.22856. Epub 2015 Aug 27.

Kimiyo Raymond 2, Martin Kircher 3, Kati J Buckingham 4, Tim Wood 5, Jay Shendure 3, Deborah A Nickerson 3, Michael J Bamshad 3 4; University of Washington Center for Mendelian Genomics; Jonathan T S Wong 1, Fabiola Paoli Monteiro 6 7, Brett H Graham 8, Sheryl Jackson 9, Rebecca Sparkes 9, Angela E Scheuerle 10, Sara Cathey 5, Fernando Kok 7 11, James B Gibson 12, Hudson H Freeze 1

Affiliations

Case Reports

Expanding the Molecular and Clinical Phenotype of SSR4-CDG

Bobby G Ng et al. Hum Mutat. 2015 Nov.

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.

Keywords: SSR4; carbohydrate-deficient transferrin; congenital disorders of glycosylation; signal sequence receptor 4; translocon complex.

© 2015 WILEY PERIODICALS, INC.

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Figures

Figure 1

Figure 1. Mutation schematic of SSR4 mutations and Western blot analysis from patient fibroblasts

(A) Schematic representation of human SSR4 gene showing the positions of the identified mutations presented in our cohort. Coding regions are depicted as black boxes with appropriate exon number listed above. For cDNA numbering, +1 represents the A of the ATG translation initiation codon in the reference sequence, with the initiation codon as codon 1. (B) Western blot analysis of SSR4 protein from a total of six cases, including the index case reported by Losfeld et al. GM00038, GM01652 and GM03348 are commercially available primary fibroblast lines from apparently healthy individuals. Western blot detection of alpha-Tubulin was used as a loading control.

Figure 2

Figure 2. Summary Clinical phenotype

Clinical information was compiled on the nine affected males including the index case reported by Losfeld et al. and summarized.

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