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01.07.2012 | Original Article

Familial renal glucosuria: a clinicogenetic study of 23 additional cases

verfasst von: HyunKyung Lee, Kyoung Hee Han, Hye Won Park, Jae Il Shin, Chan Jong Kim, Mee Kyung Namgung, Kee Hyuck Kim, Ja Wook Koo, Woo Young Chung, Dae-Yeol Lee, Su-Yung Kim, Hae Il Cheong

Erschienen in: Pediatric Nephrology | Ausgabe 7/2012

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Abstract

Background

Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia that is caused by mutations in the sodium-glucose cotransporter SGLT2 coding gene, SLC5A2.

Objective

We conducted molecular and phenotype analyses of a cohort of 23 unrelated Korean children with FRG.

Methods

Mutational analysis of the SLC5A2 gene was conducted in this multicenter study organized by the Korean Society of Pediatric Nephrology.

Results

A total of 21 different SLC5A2 mutations were detected, including 19 novel mutations. All patients had at least one mutated allele; ten patients had homozygous or compound heterozygous mutations and 13 patients had a single heterozygous mutation. Most mutations were private. Patients with two mutations were diagnosed earlier with larger amounts of urinary glucose excretion than patients with single mutations. Pedigree analysis data were consistent with the inheritance of a codominant trait with incomplete penetrance.

Conclusions

These findings extend the allelic heterogeneity in FRG and confirm previous observations of inheritance and genotype–phenotype correlation in patients with this disease.

Santer R, Kinner M, Schneppenheim M, Hillebrand G, Kemper M, Ehrich J, Swift P, Skovby F, Schaub J (2000) The molecular basis of renal glucosuria: mutations in the gene for a renal glucose transporter (SGLT2) [Abstract]. J Inherit Metab Dis 23(Suppl 1):178

van den Heuvel LP, Assink K, Willemsen M, Monnens L (2002) Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum Genet 111:544–547PubMedCrossRef

Santer R, Kinner M, Lassen CL, Schneppeheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JHH, Kemper M, Volti SL, Neuhaus T, Skovby F, Swift PGF, Schaub J, Klaerke D (2003) Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol 14:2873–2882PubMedCrossRef

Francis J, Zhang J, Farhi A, Carey H, Geller DS (2004) A novel SGLT2 mutation in a patient with autosomal recessive renal glucosuria. Nephrol Dial Transplant 19:2893–2895PubMedCrossRef

Kleta R, Stuart C, Gill FA, Gahl WA (2004) Renal glucosuria due to SGLT2 mutations. Mol Genet Metab 82:56–58PubMedCrossRef

Calado J, Soto K, Clemente C, Correia P, Rueff J (2004) Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria. Hum Genet 114:314–316PubMedCrossRef

Magen D, Sprecher E, Zelikovic I, Skorecki K (2005) A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria. Kidney Int 67:34–41PubMedCrossRef

Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J (2006) Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Kidney Int 69:852–855PubMedCrossRef

Calado J, Sznajer Y, Metzger D, Rita A, Hogan MC, Kattamis A, Scharf M, Tasic V, Greil J, Brinkert F, Kemper MJ, Santer R (2008) Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion. Nephrol Dial Transplant 23:3874–3879PubMedCrossRef

10.

Yu L, Lv J-C, Zhou X, Zhu L, Hou P, Zhang H (2011) Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients. Hum Genet 129:335–344PubMedCrossRef

11.

Wells RG, Pajor AM, Kanai Y, Turk E, Wright EM, Hediger MA (1992) Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. Am J Physiol 263:F459–F465PubMed

12.

Kanai Y, Lee WS, You G, Brown D, Hediger MA (1994) The human kidney low affinity Na⁺/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 93:397–404PubMedCrossRef

13.

Wright EM (2001) Renal Na⁺-glucose cotransporters. Am J Physiol Renal Physiol 280:F10–F18PubMed

14.

Santer R, Calado J (2010) Familial renal glucosuria and SGLT2: from a Mendelian trait to a therapeutic target. Clin J Am Soc Nephrol 5:133–141PubMedCrossRef

15.

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

16.

Santer R, Schneppenheim R, Dombrowski A, Gotze H, Steinmann B, Schaub J (1997) Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nature Genet 17:324–326PubMedCrossRef

17.

Scholl-Bürgi S, Santer R, Ehrich JHH (2004) Long-term outcome of renal glucosuria type 0: the original patient and his natural history. Nephrol Dial Transplant 19:2394–2396PubMedCrossRef

18.

Chao EC, Henry RR (2010) SGLT2 inhibition - a novel strategy for diabetes treatment. Nat Rev Drug Discov 9:551–559PubMedCrossRef

Titel: Familial renal glucosuria: a clinicogenetic study of 23 additional cases
verfasst von: HyunKyung Lee
Kyoung Hee Han
Hye Won Park
Jae Il Shin
Chan Jong Kim
Mee Kyung Namgung
Kee Hyuck Kim
Ja Wook Koo
Woo Young Chung
Dae-Yeol Lee
Su-Yung Kim
Hae Il Cheong
Publikationsdatum: 01.07.2012
Verlag: Springer-Verlag
Erschienen in: Pediatric Nephrology / Ausgabe 7/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-012-2109-9

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Familial renal glucosuria: a clinicogenetic study of 23 additional cases