A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature
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Pyrophosphate synthetase-1(PRS-1) is a crucial enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) with substrate: adenosine triphosphate (ATP) and ribose-5-phophate(R5P) in the de novo pathways of purine and pyrimidine nucleotide synthesis. Mutation in PRPS1 can result in a series of diseases of purine metabolism, which includes PRS-1 superactivity. The common clinical phenotypes are hyperuricemia and hyperuricosuria. We identified a novel missense mutation in X-chromosomal gene PRPS1 in a young Chinese woman while her mother has heterogeneous genotype and phenotype. A 24-year-old Chinese female patient suffered hyperuricemia, gout, and recurrent hyperpyrexia for more than 6 years, and then was diagnosed with hyperandrogenism, insulin resistance (IR), and polycystic ovary syndrome (PCOS). A novel missense mutation, c.521(exon)G>T, p.(Gly174Val) was detected by next-generation sequencing (NGS) and confirmed by Sanger sequencing in the patient and her parents. Interestingly, her mother has the same heterozygous missense mutation but without uric acid overproduction which can be explained by the phenomenon of the skewed X-chromosome inactivation. The substituted amino acid Val for Gly174 is positioned in the pyrophosphate (PPi) binding loop, and this mutation impacts the binding rate of Mg2+-ATP complex to PRS-1, thus the assembling of homodimer is affected by changed Val174 leading to the instability of the allosteric site. Our report highlights the X-linked inheritance of gout in females caused by mutation in PRPS1 accompanied with severe metabolic disorders and recurrent hyperpyrexia.
KeywordsGout Metabolism disorder PRPS1 PRS-1 superactivity
We thank the proband and her family for collaboration in this study. We thank the Chigene (Beijing) Translational Medical Research Center Co. Ltd for great help in genetic testing.
This work was supported by a grant from Science Technology Department of Zhejiang Province of China (grant number 2012R10038 to Xiao-Xiao Song), a grant from Zhejiang Provincial Medical and Health Technology Project (grant number 2013KYA089 to Xiao-Xiao Song), and a grant from National Natural Science Foundation of China (grant number 81300083 to Xiao-Xiao Song).
Compliance with ethical standards
This study was approved by the Ethnic Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. This study was performed according to the Helsinki Declaration. Written informed consent was obtained from the proband and her parents for the publication of this case report
The funders had no role in study design, date collection and analysis, decision to publish or preparation of the manuscript.
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