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Blanka Stiburkova, Hiroshi Miyata, Jakub Závada, Michal Tomčík, Karel Pavelka, Gabriela Storkanova, Yu Toyoda, Tappei Takada, Hiroshi Suzuki, Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout: biochemical, molecular genetics and functional analysis, Rheumatology, Volume 55, Issue 1, January 2016, Pages 191–194, https://doi.org/10.1093/rheumatology/kev350
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Sir, Gout is caused by hyperuricaemia. Several genes involved in renal urate transport, such as SLC2A9, ABCG2 and SLC22A12, have been identified as risk factors for hyperuricaemia and gout [1–5]. More recently, a genome-wide association study of gout uncovered that single-nucleotide polymorphisms (SNPs) of SLC2A9 and ABCG2 are associated with two types of gout, renal underexcretion and renal overload, respectively [6]. The genome-wide association study, however, has limitations in establishing causality of disease-associated SNPs. Therefore, experimental validations are essential to determine if interesting variants are indeed responsible for clinical symptoms. As reported in our previous study of common SLC2A9 allelic variants, we detected variants with no evidence of an association with hyperuricaemia and gout [7]. In this letter we present a biochemical, molecular genetic and functional case study suggesting a causal link between a hitherto undescribed sequence variant in the ABCG2 gene and a severe gouty phenotype.
The patient, a participant of our study on common SLC2A9 allelic variants [7], was a 47-year-old male who started having gout attacks at the age of 29 years. His medical history was unremarkable and no close relative was known to have gout or hyperuricaemia. Unfortunately, none of his close relatives agreed to an analysis of their biological material. When first seen in our clinic, he already suffered from chronic debilitating polyarthritis with widespread bulky tophi located mainly on his hands and feet and around the elbows and knees, with intermittent discharge of a chalky substance (supplementary Fig. S1, available at Rheumatology Online). Monosodium urate crystals were microscopically verified from the SF aspirated from his knee. Without treatment his serum uric acid level was 647 μmol/l.
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