PMID- 10036327
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1453
IP  - 2
DP  - 1999 Feb 24
TI  - Missense mutations in SGLT1 cause glucose-galactose malabsorption by trafficking 
      defects.
PG  - 297-303
AB  - Glucose-galactose malabsorption (GGM) is an autosomal recessive disorder caused
      by defects in the Na+/glucose cotransporter (SGLT1). Neonates present with severe
      diarrhea while on any diet containing glucose and/or galactose [1]. This study
      focuses on a patient of Swiss and Dominican descent. All 15 exons of SGLT1 were
      screened using single stranded conformational polymorphism analyses, and aberrant
      PCR products were sequenced. Two missense mutations, Gly318Arg and Ala468Val,
      were identified. SGLT1 mutants were expressed in Xenopus laevis oocytes for
      radiotracer uptake, electrophysiological experiments, and Western blotting.
      Uptakes of [14C]alpha-methyl-d-glucoside by the mutants were 5% or less than that
      of wild-type. Two-electrode voltage-clamp experiments confirmed the transport
      defects, as no noticeable sugar-induced current could be elicited from either
      mutant [2]. Western blots of cell protein showed levels of each SGLT1 mutant
      protein comparable to that of wild-type, and that both were core-glycosylated.
      Presteady-state current measurements indicated an absence of SGLT1 in the plasma 
      membrane. We suggest that the compound heterozygote missense mutations G318R and 
      A468V lead to GGM in this patient by defective trafficking of mutant proteins
      from the endoplasmic reticulum to the plasma membrane.
FAU - Lam, J T
AU  - Lam JT
AD  - Department of Physiology, UCLA School of Medicine, 10833 Le Conte Avenue, Los
      Angeles, CA 90095-1751, USA.
FAU - Martin, M G
AU  - Martin MG
FAU - Turk, E
AU  - Turk E
FAU - Hirayama, B A
AU  - Hirayama BA
FAU - Bosshard, N U
AU  - Bosshard NU
FAU - Steinmann, B
AU  - Steinmann B
FAU - Wright, E M
AU  - Wright EM
LA  - eng
GR  - DK44582/DK/NIDDK NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (SLC5A1 protein, human)
RN  - 0 (Sodium-Glucose Transporter 1)
RN  - IY9XDZ35W2 (Glucose)
RN  - X2RN3Q8DNE (Galactose)
SB  - IM
MH  - Cell Membrane/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Female
MH  - Galactose/*metabolism
MH  - Glucose/*metabolism
MH  - Humans
MH  - Infant, Newborn
MH  - Malabsorption Syndromes/*genetics/metabolism
MH  - Membrane Glycoproteins/chemistry/*genetics
MH  - Monosaccharide Transport Proteins/chemistry/*genetics
MH  - Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sodium-Glucose Transporter 1
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - S0925-4439(98)00109-4 [pii]
AID - 10.1016/s0925-4439(98)00109-4 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1999 Feb 24;1453(2):297-303. doi:
      10.1016/s0925-4439(98)00109-4.