A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature.

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.

Glial modulation of vibrissal sensory processing in rats.

Interactions between neurons and glial cells in the brain have important roles in brain functions such as development and plasticity of neural circuits or functions. Glial cells are much more actively involved in brain functions than previously thought. Here, we used vibrissal stimuli to induce sensoryevoked responses and multiunit spikes in the contralateral barrel cortex in a rat model. Local application of the gliotoxin DL-alpha-aminoadipate (AA) revealed that glial cells were involved in the sensoryevoked responses. The increases in the amplitude of somatosensory-evoked potential (SEP) and multiunit sensory-evoked spike rates in barrel cortex after AA injection were dramatic. Immunohistochemical staining of brain lipid binding protein (BLBP) and NeuN showed AA decreased cell number of astrocytes but not neurons in the barrel cortex. In conclusion, our results suggested an important role for astrocyte metabolism in normal synaptic activities.