Fig. 1

Identification and functional validation of a novel dysfunctional variant p.I242T (c.725T>C) in urate transporter ABCG2 in a family with early-onset hyperuricemia and gout. a Pedigree of a Czech family with early-onset hyperuricemia and gout. Electropherograms of partial sequences of ABCG2 show the heterozygous point mutation (c.725T>C) found in the present study; each image was a representative result. P, proband; y, years old; sU, serum urate. Hyperuricemia was defined as sU levels more than 420 μmol/L (for men) or 360 μmol/L (for women and children under 15 years) on two repeated measurements, taken at least 4 weeks apart. b Immunoblot of whole cell lysate samples. α-Tubulin, a loading control. WT, wild-type. c Intracellular localization. Confocal microscopic images were obtained 48 h after the transfection. Nuclei were stained with TO-PRO-3 iodide (gray). Bars, 10 μm. d Immunoblot of plasma membrane vesicles. Na⁺/K⁺ ATPase, a loading control. All analytical samples were prepared from transiently ABCG2-expressing 293A cells 48 h after plasmid transfection (b–d). e Urate transport activities. Data are expressed as the mean ± SD. n = 4. Statistical analyses for significant differences were performed using a two-sided t-test (**, P < 0.01; NS, not significantly different between groups)