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Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption


Cotransporters harness ion gradients to drive ‘active’ transport of substrates into cells, for example, the Na+/glucose cotransporter (SGLT1) couples sugar transport to Na+ gradients across the intestinal brush border1. Glucose-Galactose Malabsorption (GGM) is caused by a defect in SGLT1. The phenotype is neonatal onset of diarrhea that results in death unless these sugars are removed from the diet2–4. Previously we showed that two sisters with GGM had a missense mutation in the SGLT1 gene5. The gene has now been screened in 30 new patients, and a heterologous expression system has been used to link the mutations to the phenotype.

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  1. 1

    Wright, E.M., Hirayama, B.A., Loo, D.D.F., Turk, E & Hager, K. Intestinal Sugar Transport. In Physiology of the Gastrointestinal Tract, (ed. Johnson, L.R.)1751–1772 (New York, Raven, 1994).

  2. 2

    Lindquist, B. & Meeuwisse, G.W. Chronic diarrhoea caused by monosaccharide malabsorption. Acta Paediatrica 51, 674–685 (1962).

  3. 3

    Laplane, R., Polonovski, C., Etienne, M., Debray, P., Lods, J.C. & Pissaro, B. L'intolerance aux sucres a transfert intestinal actif Ses rapports avec l'intolerance au lactose et le syndrome coeliaque. Arch. Fr. Pediatr. 19, 895 (1962).

  4. 4

    Desjeux, J.-R., Turk, E. & Wright, E.M., Na+D-Glucose cotransport defects leading to renal glycosuria and congenital selective intestinal malabsorption of glucose and galactose. In Metabolic Basis of Inherited Disease, Vol. 3 (eds Scriver, C.R., Beaudet, A.L. & Sly, W.S.) 3563–3580 (New York, McGraw-Hill, 1995).

  5. 5

    Turk, E., Zabel, B., Mundlos, S., Dyer, J. & Wright, E.M. Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature 350, 354–356 (1991).

  6. 6

    Loo, D.D.F., Hazama, A., Supplisson, S., Turk, E. & Wright, E.M. Relaxation kinetics of the Na+/glucose cotransporter. Proc. Natl. Acad. Sci. USA 90, 5767–5771 (1993).

  7. 7

    Zampighi, G.A. et al. A method for determining the unitary functional capacity of cloned channels and transporters expressed in Xenopus laevis oocytes. J. Mem. Biol. 148, 65–78 (1995).

  8. 8

    Mount, S.M. A Catalogue of Splice Junction Sequences. Nucl Acids Res. 10, 459–473 (1982).

  9. 9

    Panayotova-Heiermann, M., Loo, D.D.F., Lostao, M.P. & Wright, E.M. Sodium/D-glucose cotransporter charge movements involve polar residues. J. Biol. Chem. 269, 21016–21020 (1994).

  10. 10

    Hediger, M.A., Coady, M.J., Ikeda, T.S. & Wright, E.M. Expression cloning and cDNA sequencing of the Na+/glucose cotransporter. Nature 330, 379–381 (1987).

  11. 11

    Mackenzie, B., Panayotova-Heiermann, M., Loo, D.D.F., Lever, J.E. & Wright, E.M. SAAT1 is a low affinity NaVglucose cotransporter and not an amino acid transporterA interpretation. J. Biol. Chem. 269, 22488–22491 (1994).

  12. 12

    Kwon, H.M., Yamauchi, A., Uchida, S., Preston, A.S., Garcia-Perez, A., Burg, M.B. & Handler, J.S. Cloning of the cDNA of Na+/myo-inositol cotransporter, a hypertoncity stress protein. J. Biol. Chem. 6297–6301 (1992).

  13. 13

    Stirling, C.E., Schneider, A.J., Wong, M.-D. & Kinter, W.B. Quantitative radioqutography of sugar transport in intestinal biopsies from normal humans and a patient with glucose-galactose malabsorption. J.Clin. Invest. 51, 438–451 (1972).

  14. 14

    Lostao, M.P., Hirayama, B.A., Panayotova-Heiermann, M., Sampogna, S.L., Bok, D. & Wright, E.M. Arginine-427 in the Na/glucose cotransporter (SGLT1) is involved in trafficking to the plasma membrane. FEES Lett. 377, 181–184 (1995).

  15. 15

    Turk, E., Martín, M.G. & Wright, E.M. Structure of the human NaVglucose cotransporter gene SGLTl. J. Biol. Chem. 269, 15204–15209 (1994).

  16. 16

    Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5, 874–879 (1989).

  17. 17

    Higuchi, R.B., Krummel, B. & Saiki, R.K. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions.Nucl. Acids Res. 16, 7351–7367 (1986).

  18. 18

    Ikeda, T.S., Hwang, E.S., Coady, M.J., Hirayama, B.A., Hediger, M.A. & Wright, E.M. Characterization of a Na+/glucose cotransporter cloned from rabbit small intestine. J. Mem. Biol. 110, 87–95 (1989).

  19. 19

    Hirayama, B.A. and Wright, E.M. Glycosylation of the rabbit intestinal brush border Na+/glucose cotransporter. Biochim. Biophys. Acta 1103, 37–44 (1992).

  20. 20

    Parent, L., Supplisson, S., Loo, D.D.F. & Wright, E.M. Electrogenic properties of the cloned Na+/glucose cotransporter: I Voltage-Clamp studies. J. Mem. Biol. 125, 49–62 (1992).

  21. 21

    Turk, E., Kerner, C.J., Lostao, M.P. & Wright, E.M., Topology of the Human Na+/glucose Cotransporter SGLT1. J Biol. Chem. 271, 1925–1934 (1996).

  22. 22

    Krawczak, M., Reiss, J. & Cooper, D.N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet. 90, 41–54 (1992).

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