Background
Hereditary renal hypouricemia (HRH) is a genetically heterogenetic disease. Patients with HRH are almost asymptomatic; but some may experience exercise-induced acute kidney injury (EAKI) and nephrolithiasis which may bring concerns regarding the risk-benefit ratio as marginal kidney donors. This study examined the pathogenic mutations of hypouricemia in two recipients after receiving kidney transplantation, providing preliminary evidence for the mechanism of hypouricemia.
Conclusions
Two novel mutations of SLC22A12 were identified. Preliminary functional analysis revealed a potential deleterious effect of these mutations in the grafts derived from the donor and sequencing analysis expand the molecular mechanisms of renal hypouricemia.
Methods
Two participants underwent detailed biochemical examinations. DNA and RNA were extracted from transplant specimens for sequencing. The whole-genome sequencing and polymerase chain reaction (PCR) amplification were performed to confirm the pathogenic genes. Functional effects of mutant proteins were verified by bioinformatics analysis. RNA-sequencing (RNA-seq) was used to study the transcriptome of hypouricemia.
Results
Both of the recipients had the low serum uric acid (UA) (45-65 µmol/l), high fraction excretion of UA (44% and 75%) and an increase in the UA clearance (35.9 and 73.3 mL/min) with a functioning graft. The sequencing analyses revealed 7 kinds of potential mutational genes in this case, two novel mutations p.R89H and p.L181V in SLC22A12 gene which were revealed by bioinformatics could be pathogenic in nature. Conclusions: Two novel mutations of SLC22A12 were identified. Preliminary functional analysis revealed a potential deleterious effect of these mutations in the grafts derived from the donor and sequencing analysis expand the molecular mechanisms of renal hypouricemia.