Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib)

E. Schollen, L. Dorland, T. J. De Koning, O. P. Van Diggelen, J. G.M. Huijmans, T. Marquardt, D. Babovic-Vuksanovic, M. Patterson, F. Imtiaz, B. Winchester, M. Adamowicz, E. Pronicka, H. Freeze, G. Matthijs

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

CDG-Ib is the 'gastro-intestinal' type of the congenital disorders of glycosylation (CDG) and a potentially treatable disorder. It has been described in patients presenting with congenital hepatic fibrosis and protein losing enteropathy. The symptoms result from hypoglycosylation of serum and other glycoproteins. CDG-Ib is caused by a deficiency of mannose-6-phosphate isomerase (synonym: phosphomannose isomerase, EC 5.3.1.8), due to mutations in the MPI gene. We determined the genomic structure of the MPI gene in order to simplify mutation detection. The gene is composed of 8 exons and spans only 5 kb. Eight (7 novel) different mutations were found in seven patients with a confirmed phosphomannose isomerase deficiency, analyzed in the context of this study: six missense mutations, a splice mutation and one insertion. In the last, the mutation resulted in an unstable transcript, and was hardly detectable at the mRNA level. This emphasizes the importance of mutation analysis at the genomic DNA level. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)247-252
Number of pages6
JournalHuman mutation
Volume16
Issue number3
DOIs
StatePublished - Jan 1 2000

    Fingerprint

Keywords

  • CDG
  • Carbohydrate deficient glycoprotein syndrome
  • MPI
  • Mannose therapy
  • Mannosephosphate isomerase
  • Metabolic disorders
  • Mutation database
  • Phosphomannose isomerase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Schollen, E., Dorland, L., De Koning, T. J., Van Diggelen, O. P., Huijmans, J. G. M., Marquardt, T., Babovic-Vuksanovic, D., Patterson, M., Imtiaz, F., Winchester, B., Adamowicz, M., Pronicka, E., Freeze, H., & Matthijs, G. (2000). Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib). Human mutation, 16(3), 247-252. https://doi.org/10.1002/1098-1004(200009)16:3<247::AID-HUMU7>3.0.CO;2-A