Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting.
Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia. Mutations in the sodium/glucose co-transporter SGLT2 coding gene, SLC5A2, were recently found to be responsible for the disorder. Here, we report the molecular and phenotype study of five unrelated FRG families. Five patients were identified and their family members screened for glucosuria. SLC5A2 coding region of index cases was polymerase chain reaction amplified and sequenced. Five different mutations are reported, including four novel alleles. The IVS12+1G>A and p.A102V alleles were identified in homozygosity in index patients of two unrelated families. A proband from another family was compound heterozygous for the p.R132H and p.A219T mutations, and the heterozygous p.Q167fsX186 frameshift allele was the only mutation detected in the affected individual from an additional pedigree. For the remaining family no mutations were detected. The patient homozygous for the p.A102V mutation had glucosuria of 65.6 g/1.73 m(2)/24 h, evidence of renal sodium wasting, mild volume depletion, and raised basal plasma renin and serum aldosterone levels. Our findings confirm previous observations that in FRG, transmitted as a codominant trait with incomplete penetrance, most mutations are private. In the only patient with massive glucosuria in our cohort there was evidence evocative of renin-angiotensin aldosterone system activation by extracellular volume depletion induced by natriuresis. Definite proof of renin-angiotensin aldosterone system activation in FGR should rely on evaluation of additional patients with massive glucosuria.
Calado
J
J
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Rua da Junquiera no. 96, 1349-008 Lisbon, Portugal. jcalado.gene@fcm.unl.pt
Loeffler
J
J
Sakallioglu
O
O
Gok
F
F
Lhotta
K
K
Barata
J
J
Rueff
J
J
D004252:DNA Mutational Analysis; D005260:Female; D006030:Glycosuria, Renal / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012965:Sodium Chloride / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics*
C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D012965:Sodium Chloride