Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Vibeke Westphal, Sandra Peterson, Marc Patterson, Anne Tournay, Andrea Blumenthal, Eileen P. Treacy, Hudson H. Freeze

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Purpose: Congenital disorders of glycosylation (CDG) result from mutations in N-glycan biosynthesis. Mutations in phosphomannomutase (PMM2) cause CDG-Ia. Here, we report four clinically mild patients and their mutations in PMM2. Methods: Analysis of the PMM2 cDNA and gene revealed the mutations affecting the glycosylation efficiency. Results: The patients have 30% to 50% normal PMM activity in fibroblasts due to different mutations in PMM2, and we studied the effect of each mutation on the PMM activity in a Saccharomyces cerevisiae expression system. Conclusions: Each patient carried a severe mutation that decreased the PMM activity to less than 10% as well a relatively mild mutation. A new mutation, deletion of base 24, changed the reading frame. The C9Y, C241S, and L32R mutations showed 27% to 45% activity when expressed in the eukaryotic expression system, and the more severe D148N was shown to be thermolabile.

Original languageEnglish (US)
Pages (from-to)393-398
Number of pages6
JournalGenetics in Medicine
Volume3
Issue number6
DOIs
StatePublished - Jan 1 2001

Keywords

  • Congenital disorders of glycosylation
  • Genotype-phenotype
  • Oligosaccharide
  • Phosphomannomutase

ASJC Scopus subject areas

  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia'. Together they form a unique fingerprint.

  • Cite this

    Westphal, V., Peterson, S., Patterson, M., Tournay, A., Blumenthal, A., Treacy, E. P., & Freeze, H. H. (2001). Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia. Genetics in Medicine, 3(6), 393-398. https://doi.org/10.1097/00125817-200111000-00003