title: 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.
abstract: 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.
authors.affiliation: Department of Cell Biology and Histology, University of Nijimegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Ouwendijk
authors.forename: C E
authors.initials: CE
authors.lastname: Moolenaar
authors.forename: W J
authors.initials: WJ
authors.lastname: Peters
authors.forename: C P
authors.initials: CP
authors.lastname: Hollenberg
authors.forename: L A
authors.initials: LA
authors.lastname: Ginsel
authors.forename: J A
authors.initials: JA
authors.lastname: Fransen
authors.forename: H Y
authors.initials: HY
authors.lastname: Naim
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D001706:Biopsy; D001944:Breath Tests; D002451:Cell Compartmentation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D006859:Hydrogen / Q000032:analysis; D008286:Malabsorption Syndromes / Q000151:congenital*; D008969:Molecular Sequence Data; D009154:Mutation; D013394:Sucrase-Isomaltase Complex / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D006859:Hydrogen; D013394:Sucrase-Isomaltase Complex