Molecular analysis of the SGLT2 gene in patients with renal glucosuria.
The role of SGLT2 (the gene for a renal sodium-dependent glucose transporter) in renal glucosuria was evaluated. Therefore, its genomic sequence and its intron-exon organization were determined, and 23 families with index cases were analyzed for mutations. In 21 families, 21 different SGLT2 mutations were detected. Most of them were private; only a splice mutation was found in 5 families of different ethnic backgrounds, and a 12-bp deletion was found in two German families. Fourteen individuals (including the original patient with 'renal glucosuria type 0') were homozygous or compound heterozygous for an SGLT2 mutation resulting in glucosuria in the range of 14.6 to 202 g/1.73 m(2)/d (81 - 1120 mmol/1.73 m(2)/d). Some, but not all, of their heterozygous family members had an increased glucose excretion of up to 4.4 g/1.73 m(2)/d (24 mmol/1.73 m(2)/d). Likewise, in index cases with glucosuria below 10 g/1.73 m(2)/d (55 mmol/1.73 m(2)/d) an SGLT2 mutation, if present, was always detected in the heterozygous state. We conclude that SGLT2 plays an important role in renal tubular glucose reabsorption. Inheritance of renal glucosuria shows characteristics of a codominant trait with variable penetrance.
Santer
René
R
Department of Pediatrics, University of Kiel, Kiel, Germany. r.santer@uke.uni-hamburg.de
Kinner
Martina
M
Lassen
Christoph L
CL
Schneppenheim
Reinhard
R
Eggert
Paul
P
Bald
Martin
M
Brodehl
Johannes
J
Daschner
Markus
M
Ehrich
Jochen H H
JH
Kemper
Markus
M
Li Volti
Salvatore
S
Neuhaus
Thomas
T
Skovby
Flemming
F
Swift
Peter G F
PG
Schaub
Jürgen
J
Klaerke
Dan
D
D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006030:Glycosuria, Renal / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index; D051297:Sodium-Glucose Transporter 2
D009004:Monosaccharide Transport Proteins; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2