The Department of Pediatrics of Peking University First Hospital has a long term of outstanding history.It was established about 60 years ago.After the division of pediatric neurology(DPN) had been established in 1960s,it had been assigned to cover genetic disorders.During the recent 20 years,efforts have been put on three aspects:(1)Pediatric neurology clinical service and education;(2)research studies of childhood epilepsies and pediatric neurogenetic disorders;and (3) development of a strong DPN team to establish a comprehensive pediatric neurological program.In this paper,we reviewed the history of the pediatric neurology division in our department,our clinical and research work and achievements for neurogenetic diseases.

SUMMARY Lysosomal storage diseases are a group of genetic disorders that result from the defect in lysosomal function. Signs and symptoms are variable, it is difficult to diagnose this group of disease merely by the clinical manifestation. The diagnosis usually is made by measuring the activity of the corresponding enzyme. Gene mutational analysis is useful for the diagnosis of some of the lysosome storage diseases. The treatment has focused on the replacement of the defective enzyme responsible for the disease and the hematopoietic stem cell transplantation. Both of them have achieved exciting outcomes in some of the diseases.

Objective: To study the expression of N-methl- D -aspartate (NMDA) receptor subunits NR2A and N R2B mRNA after audiogenic seizure in the brain of genetically epilepsy-prone ra t s-P77PMC. Methods: In situ hybridization technique was used to stud y the mRNA expre ssion of NR2A and NR2B at different times after audiogenic seizure in different b rain areas of P77PMC rats. Results: The NR2A mRNA expression showed time-depende nt down-regulation in cerebral motor and sensory cortex, hippocampus CA1-CA3, de ntate gyrus after audiogenic seizure. Down-regulation emerged 30 min after se izure, 2 hours later the mRNA reached the lowest level， 4-8 hours later re turned to the baseline, and 24 hours later decreased lower than baseline again . The mRNA expression of NR2B was quite similar to that of the NR2A af ter seizure. Conclusion: The down-regulation of NR2A and NR2B mRNA indicates that the subunit composition of the NMDA receptor complexes may be altered after aud iogenic seizure. These structural alterations could make the function of NMDA re ceptor complexes change and subsequently influence the excitability of brain as well as the susceptibility of epilepsy.

Objective： To investigate pathophysiologic mechanism about initiation and propagation of epilepsy in a genetically epilepsy-prone rat (GEPR) model. Methods： The hippocampal MF sprouting of P77PMC rats was examined at different stages in the course of recurrent seizures using Timm method of sulfide silver staining. Results：The three groups of P77PMC rats which experienced 30 and less than 30 times of audiogenic seizure ( AGS ) and the Wistar control group did not display MF sprouting in dentate gyrus, however, the group of P77PMC rats which experienced 50 times of AGS was found hippocampal MF sprouting into the inner molecular layer of dentate gyrus. Conclusion：Our findings suggest that hippocampal MF sprouting presented not only in limbic seizure, but also in AGS, the seizure initiated in brainstem but rapidly generalized; in AGS-prone rats, recurrent AGSs can induce MF synaptic reorganization in hippocampus.

Epilepsy is a kind of brain dysfunction syndrome caused by so many reasons instead of a certain disease. Abnormal neuron discharge can cause epilepsy. Idiopathic epilepsy refers to epilepsy or epilepsy syndrome without any latent reasons but inherited trait. Idiopathic epilepsy is confirmed as an ion channelopathy at present. The first genemutation was found in idiopathic epilepsy in 1995, and a lot of genes coding either voltage-gated or ligand-gated ion channels have been found since then. In the present review, some new advances in research on ion channels dysfunction in idiopathic epilepsy are summarized.

Objective To evaluate the efficacy of ultrasonically guided radiofrequency (RF) thermal ablation of hepatic carcinoma (HC) with a clustered electrode. Methods Clinical records on 245 consecutively admitted HC patients who underwent RF tissue ablation therapy were analyzed. The tumor supplying blood flow, changes of tumor size, clinical manifestation, and AFP level were analyzed. Results AFP value decreased significantly in 50% of patients one week after ablation. Tumors less than 5*!cm in diameter became avascularized 1 to 6 months after the therapy, and it was noted that all tumors shrank in size after the therapy. For tumors more than 5*!cm in diameter, RF ablation was used in conjunction with intraarterial chemotherapy and embolization. Conclusion Ultrasound guided RF thermal ablation is an effective, safe, minimally invasive technique for treating malignant hepatic tumors.

Objective:To improve previous method of primary rat cortical neuron culture to get purer and more long-lasting cells for study.Methods:Timed-pregnant Wistar rats at a gestational age of 16 or 17 days(16-17 d) were used.Fetal brains were removed and the cerebral cortices were dissected out.Papain digestion and mechanical dissociation were combined to conduct mono-cell suspending media.Four to six hours(4-6 h) post-plating,all plating media were removed from cultures and replaced with Neurobasal medium supplemented with B27.On the third day,10 ?mol/L cytosine arabinoside(Ara-C) was added to the culture for 24 h to inhibit the outgrowth of glial cells.Half of the culture medium was changed every week.The morphological changes of neuron cells were observed by light microscope.Double immuno-staining of microtubule-associated protein 2(MAP2) and karyon were applied to assess the culture purity.Evaluation of synapse formation was processed by immunocytochemical analysis using antibodies against both pre-and postsynaptic protein markers.Results:The improved method could remarkably increase the cell number and reduce neuronal damnification.The primary culture was characte-rized by high uniformity,purity,normal synapse formation and longtime livability.Conclusion:This is a simple and reliable technique for the in vitro primary culture of rat cortical neurons.

Objective: To analyze the expression of mecp2 gene at mRNA and protein;Cerebral cortex level in the cerebral cortex of the normal Wistar rat throughout development. Methods: We chose the 15th day (E15), 17th day (E17), 19th day (E19) of embryo period, the day of birth (P0), the 7th day (P7), the 14th day (P14), the 28th day (P28) of postnatal period, and adulthood as analyzing time points. The expression of mecp2 gene at mRNA level was analyzed by real time PCR and Northern blot. The expression of MeCP2 protein was analyzed by Western blot. Results: There was one type of mecp2 mRNA transcript (approximately 10 kb) expressed in the cerebral cortex of the normal Wistar rat. The expression level of mecp2 mRNA varied subtly during the development. There was one type of MeCP2 protein (75 000) expressed in the cerebral cortex of the normal Wistar rat. The expression level of MeCP2 protein remained the lowest on E15, from E19 to adulthood the expression levels of MeCP2 protein increased dramatically compared with that on E15. From P7 to adulthood, the differences of expression between two time points were subtle. Conclusion: The expression level of MeCP2 protein increases as the neurons in the cerebral cortex of normal Wistar rat grow mature. This indicates that MeCP2 protein is very important to neuron's maturation, and probably has relationship with maintaining maturation state of neurons.

Objective: To study the protection of IL 1ra in cultured developing neuron injury following Mg 2+ free induced epileptiform discharges. Methods: Rat embryo cortical neurons cultured for 6 d and 17 d were directly exposed to Mg 2+ free media, or pretreated with IL 1 receptor antagonist or NMDA receptor antagonists before being exposed to Mg 2+ free media, and then returned to regular media.MTT assay was used to study mitochondrial function injury, laser scanning confocal microscope to measure [Ca 2+ ]i, and real time RT PCR to detect gene mRNA expression. Results:(1) MTT conversion rates were higher in neurons pre and co treated with 10 mg/L IL 1ra than those of neurons with only Mg 2+ free treatment in neurons cultured for 17 d, but not in neurons cultured for 6 d.(2) [Ca 2+ ]i was lower in neurons pre and co treated with 10 mg/L IL 1ra than those of neurons with only Mg 2+ free treatment, either in neurons cultured for 6 d or in neurons cultured for 17 d, and the effects of IL 1ra on [Ca 2+ ]i change were different between neurons cultured for 6 d and neurons cultured for 17 d.(3) Pre and co treated with 10 mg/L IL 1ra NR1 mRNA expression increase induced by Mg 2+ free treatment was decreased, either in neurons cultured for 6 d or neurons cultured for 17 d, and this effect showed no difference between neurons cultured for 6 d and 17 d; Pre and co treated with 10 mg/L IL 1ra NR2A mRNA expression increase induced by Mg 2+ free treatment in neurons cultured for 17 d was decreased, and NR2A mRNA expression showed no difference between IL 1ra group and age matched control group, but have no effect on neurons cultured for 6 d; Pre and co treated with 10 mg/L IL 1ra have NR2B mRNA expression increase induced by Mg 2+ free treatment was not affected, either in neurons cultured for 6 d or neurons cultured for 17 d. Conclusion:Neuroprotection of IL 1Ra in seizure induced injury is age dependent. The mech anism of the neuroprotection of IL 1Ra includes down regulation of [Ca 2+ ]i and others.

Objective:To study the clinical and genetics features of two families with dentatorubral-pallido-luysian atrophy (DRPLA), and to summarize the correlation between genotypes and phenotypes.Methods:The peripheral blood, clinical data and auxiliary examination results of probands and related members in 2 families with hereditary epilepsy and ataxia were collected from July 2018 to March 2019 in Peking University First Hospital.By whole exome sequencing and detecting the cytosine-adenine-guanine (CAG) repeats with capillary electrophoresis and fragment analysis, the genetic testing was conducted on the probands and their family members.The clinical and genetic characteristics of all affected members in the 2 families were also analyzed.Results:Two families were diagnosed with DRPLA.All 11 patients presented with psychomotor retardation, and 7 of them had seizures (including myoclonus, focal seizures and generalized tonic-clonic seizures, etc.). There were significant differences in clinical manifestations among different patients in the same family, and the filial generation had seizures at an earlier age with a more severe phenotype than the parental generation.The youngest onset age was 2 years old, and the largest was 45 years old.Five cases had seizures in childhood.Of the 11 patients, 5 cases were deceased, and the cause of death included seizure attacks, sudden unexpected death in epilepsy (SUDEP) and disease progression.The number of CAG repeat times in the fifth exon of the ATN1 gene were found abnormal in 6 surviving patients.The grandfather of the proband in pedigree 2 had normal clinical manifestations, but he also showed abnormal CAG repeats in the fifth exon of the ATN1 gene, which might be an intermediate allele. Conclusions:DRPLA is mainly featured by epilepsy, ataxia, psychomotor retardation and anticipation in clinical.This disease is rare in children with seizures as the first symptom, and has poor prognosis.An early diagnosis can facilitate genetic counseling.