Identification of ten novel SLC5A2 mutations and determination of the renal threshold for glucose excretion in Chinese patients with familial renal glucosuria.

Background: Familial renal glucosuria (FRG) is a rare renal tubular disorder characterized by isolated persistent glucosuria without both abnormal glucose metabolism and any signs of proximal tubular dysfunction. SLC5A2 gene mutations are responsible for most FRG cases.

Methods: Quantitative test for 24-hour urine glucose and RT were determined in 9 families (totaling 25 subjects). All coding regions, including intron-exon boundaries, were analyzed with PCR followed by direct sequence analysis.

Results: Ten novel mutations were identified (c.331 T > C, p.W111R; c.374T>C, p.M125T; c.394C>T, p.R132C; c.612G>C, p.Q204H; c.829C>T, p.P277S; c.880G>A, p.D294N; c.1129G>A, p.G377S; c.1194C>A, p.F398L; c.1540C > T, p.P514S and c.1573C>T, p.H525Y). c.886(-10_-31)del that is specific to Chinese population was found in 5 out of 9 families, with a mutation rate of 28% (5/18). The compound heterozygotes presented with much lower RT values (1.28 ± 0.10 mmol/L), compared with the carriers of heterozygous variants (5.14 ± 0.77 mmol/L) (p<0.01); c.886(-10_-31)del heterozygotes had significant lower RT values than others (4.43 ± 0.37 vs 5.7 ± 0.51 mmol/L; p<0.01).

Conclusions: Ten novel SLC5A2 mutations are found and c.886(-10-31)del may be a hot spot mutation in Chinese population. Compound heterozygotes had much lower RT values than simple heterozygotes. Mixed-meal tolerance test is a simple method for determining RT in FRG patients.