A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein

Biochim Biophys Acta. 2001 May 31;1536(2-3):141-7. doi: 10.1016/s0925-4439(01)00043-6.


The Na(+)/glucose cotransporter gene SGLT1 was analyzed in a Japanese patient with congenital glucose-galactose malabsorption. Genomic DNA was used as a template for amplification by the polymerase chain reaction of each of the 15 exons of SGLT1. The amplification products were cloned and sequenced. About half of the exon 5 clones of the patient contained a C-->T transition, resulting in an Arg(135)-->Trp mutation, whereas the remaining clones contained the normal exon 5 sequence. In addition, whereas some exon 12 clones exhibited the normal sequence, others showed a CAgtaggtatcatc-->CAgacc mutation at the splice donor site of intron 12 that may result either in the skipping of exon 12 or in read-through of intron 12. Neither the Arg(135)-->Trp mutant nor either of the possible intron 12 mutant proteins exhibited Na(+)-dependent glucose transport activity when expressed in Xenopus oocytes. Immunocytochemical analysis indicated, however, that the Arg(135)-->Trp mutant was localized to the oocyte plasma membrane. DNA sequence analysis revealed that the missense mutation in exon 5 and the splice site mutation in intron 12 were inherited from the proband's father and mother, respectively. These results indicate that the patient is a compound heterozygote for this disease, and that the Arg(135)-->Trp mutant of SGLT1 undergoes normal trafficking to the plasma membrane but is non-functional.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carbohydrate Metabolism, Inborn Errors / genetics*
  • Carbohydrate Metabolism, Inborn Errors / metabolism
  • Exons
  • Female
  • Galactose / deficiency
  • Galactose / metabolism*
  • Glucose / deficiency
  • Glucose / metabolism*
  • Humans
  • Infant, Newborn
  • Malabsorption Syndromes / congenital*
  • Malabsorption Syndromes / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Monosaccharide Transport Proteins / biosynthesis
  • Monosaccharide Transport Proteins / chemistry
  • Monosaccharide Transport Proteins / genetics*
  • Mutation, Missense*
  • Oocytes / metabolism
  • Pedigree
  • Sodium-Glucose Transporter 1
  • Xenopus


  • Membrane Glycoproteins
  • Monosaccharide Transport Proteins
  • SLC5A1 protein, human
  • Sodium-Glucose Transporter 1
  • Glucose
  • Galactose