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

    loading  Checking for direct PDF access through Ovid


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 mannoserich 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 fulllength 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. (J. Clin. Invest. 1996. 97:633-641.) Key words: ERGIC-53 centered dot intestine centered dot processing centered dot quality control centered dot retention

    loading  Loading Related Articles