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.

Astrocyte-restricted disruption of connexin-43 impairs neuronal plasticity in mouse barrel cortex.

There is intensive gap-junctional coupling between glial processes, but their significance in sensory functions remains unknown. Connexin-43 (Cx43), a major component of astrocytic gap-junction channels, is abundantly expressed in astrocytes. To investigate the role of Cx43-mediated gap junctions between astrocytes in sensory functions, we generated Cx43 knockout (KO) mice with a mouse line carrying loxP sites flanking exon 2 of the Cx43 gene and the transgenic line expressing Cre recombinase under control of the glial fibrillary acidic protein promoter, which exhibited a significant loss of Cx43 in astrocytes in the barrel cortex. Although Cx43 expression between the astrocytes measured by immunohistochemistry was virtually abolished in Cx43 KO mice, they had normal architecture in the barrel cortex but the intensity of cytochrome oxide histochemistry decreased significantly. In vivo electrophysiological analysis revealed that the long-term potentiation of the vibrissal evoked responses in the barrel cortex evoked by high-frequency rhythmic vibrissal stimuli (100 Hz, 1 s) was abolished in Cx43 KO mice. Current source density analysis also revealed that astrocytic Cx43 was important to the flow of excitation within the laminar connections in barrel cortex. Behavioral tests showed that the ability of Cx43 KO mice to sense the environment with their whiskers decreased. Even so, the jump-stand experiment showed that they could still discriminate rough from smooth surfaces. Our findings suggest that Cx43-mediated gap-junctional coupling between astrocytes is important in the neuron-glia interactions required for whisker-related sensory functions and plasticity.

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.

[Gap junction and function of brain].

Gap junction is the aggregate of some intercellular channels, which allows ions and small molecules to transport or transfer between cells. There are about 20 proposed members of the connexin family found in mammalian tissues now, and more than 10 reported are expressed in the nervous system. The astrocytes and oligodendrocytes express some specific connexins. In the present article, we review the recent literatures to illustrate the importance of gap junction for the intercellular communication between glial cells, astrocytes and neurons, and neuronal cells, which is crucial for brain functions.

Benign infantile convulsions with mild gastroenteritis: clinical analysis of 40 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the pathogenesis, clinical characteristics and treatment of benign infantile convulsions with mild gastroenteritis (BICG).</p><p><b>METHODS</b>The clinical manifestations and laboratory findings were observed in 40 children with BICG. The antigen and antibodies of rotavirus and calicivirus in stool and cerebral spinal fluid (CSF) were tested by the golden standard method and ELISA. The neurological outcome was evaluated by a follow-up of six months or more.</p><p><b>RESULTS</b>All of the 40 children had mild gastroenteritis with or without minor dehydration. Cluster convulsions were observed in these children. There were normal findings in blood biochemistry (Na+, K+, Ca2+, Cl-, HCO3-, glucose) and cerebral CT or MRI examinations. The interictal EEG showed sprinkle central or frontal epileptiform discharges in 8 children; clear central and parietal epileptiform discharges in 1 child; and no abnormal findings were observed in the other 31 children. Positive rotavirus antigen was detected in 11 children and positive calicivirus antigen in stool samples in 4 children. Positive antibodies of rotavirus and calicivirus in CSF were not seen. Seizures recurred in 22 of 28 children who received prophylactic injections of phenobarbital(5-10 mg/kg). In a 6 months follow-up, one child developed epilepsy and the other 39 children had no seizures and neurological sequelae.</p><p><b>CONCLUSIONS</b>The digestive system manifestations are mild in children with BICG. Convulsions are always clustered in these children. The mechanism underlying convulsions is not clear. Conventional dose of phenobarbital is not effective for prevention of seizures. Most of children with BICG have a good prognosis.</p>

Interictal epileptiform discharges in children with epilepsy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the features of interictal epileptiform discharges (IED) during sleep and wakefulness in children with epilepsy.</p><p><b>METHODS</b>The polysomnography, active EEG and video EEG were performed on 48 children with epilepsy during the whole night, and wakefulness of pre- and post-sleep. The epileptiform sharp/spike discharge indexes during sleep and wakefulness were recorded. The positive rate of IED in focal and generalized epilepsy was compared.</p><p><b>RESULTS</b>Of the 48 patients, 25 showed IED, including 9 cases (36.0%) in the generalized seizure group and 16 cases (64.0%) in the focal seizure group (P<0.05). The epileptiform sharp/spike discharge indexes in the whole non-rapid eye movement (NREM) sleep stage (stages S1-S4: 21.13+/-19.96, 19.59+/-17.76, 22.85+/-18.99, and 20.37+/-16.63) were significantly higher than that in the wakefulness stage (8.20+/-6.21) (P<0.05). The discharge index in the S3 stage during NREM sleep was higher than that during the rapid eye movement (REM) sleep (22.85+/-18.99 vs 12.91+/-10.95; P<0.05).</p><p><b>CONCLUSIONS</b>The positive rate of IED in the focal seizure group was higher than that in the generalized seizure group. Sleep, especially NREM sleep, facilitates IED in children with epilepsy.</p>

Behavior Characteristics in Children with Benign Epilepsy Combined with Centro-Temporal Spikes / 实用儿科临床杂志

Objective To explore the behavior characteristics in children with benign epilepsy combined with centro-temporal spikes(BECTS).Methods Eighty-two children with BECTS aged 2.5-3.0(2.65?2.31)years old,51 male,31 female,who were free of mental retardation assessed with Gesell developmental schedules,untreated with antiepileptic drugs,and were investigated 15 days after the latest seizure.Eighty-two healthy children with sex and age matched to the cases,53 male,29 female,aged 2.5-3.0(2.6?0.4)years old.The behavior characteristics of infants in BECTS group and control group were assessed with CBCL,including 6 behavior factors which were sleep problem,social flinches,depression,physical aspect,attacking,act of sabotage and the infants-middle school student social ability scale.Results The total scores of behavior characteristics and the scores of depression,sleep problem,attacking and act of sabotage in BECTS group were all higher than those in control group,the differences were statistically significant.However,scores of social flinches,and physical aspect in BECTS group had no significant differences compared with those of control group.There were no significant difference of social adaptive component between the BECTS and control group.Conclusions Children with BECTS have behavior disorders to some extent,but their social adaptive capacity are the same as normal children.