Congenital sucrase-isomaltase deficiency. Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment

J Clin Invest. 1996 Feb 1;97(3):633-41. doi: 10.1172/JCI118459.


Congenital sucrase-isomaltase deficiency is an example of a disease in which mutant phenotypes generate transport-incompetent molecules. Here, we analyze at the molecular level a phenotype of congenital sucrase-isomaltase deficiency in which sucrase-isomaltase (SI) is not transported to the brush border membrane but accumulates as a mannose-rich precursor in the endoplasmic reticulum (ER), ER-Golgi intermediate compartment, and the cis-Golgi, where it is finally degraded. A 6-kb clone containing the full-length cDNA encoding SI was isolated from the patient's intestinal tissue and from normal controls. Sequencing of the cDNA revealed a single mutation, A/C at nucleotide 3298 in the coding region of the sucrase subunit of the enzyme complex. The mutation leads to a substitution of the glutamine residue by a proline at amino acid 1098 (Q1098P). The Q1098P mutation lies in a region that is highly conserved between sucrase and isomaltase from different species and several other structurally and functionally related proteins. This is the first report that characterizes a point mutation in the SI gene that is responsible for the transport incompetence of SI and for its retention between the ER and the Golgi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Biological Transport
  • Biopsy
  • Breath Tests
  • Cell Compartmentation
  • Endoplasmic Reticulum / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Hydrogen / analysis
  • Malabsorption Syndromes / congenital*
  • Molecular Sequence Data
  • Mutation
  • Sucrase-Isomaltase Complex / deficiency*
  • Sucrase-Isomaltase Complex / genetics
  • Sucrase-Isomaltase Complex / metabolism
  • Transfection


  • Hydrogen
  • Sucrase-Isomaltase Complex