Objective:To summarize the clinical characteristics of patients with epilepsy caused by focal cortical dysplasia (FCD), and identify the influencing factors for postoperative seizure controls.Methods:Fifty-seven patients with epilepsy caused by FCD admitted to Department of Neurosurgery, Third Affiliated Hospital of Zhengzhou University from July 2019 to November 2023 were chosen; standard preoperative evaluation, surgery, postoperative management and follow-up were performed. A retrospective study of clinical data, imaging and video electroencephalogram (VEEG) data, surgical approaches, pathological findings, and follow-up data was performed; influencing factors for postoperative seizure controls were analyzed.Results:In these 57 patients with epilepsy caused by FCD, 29 were males (50.88%) and 28 were females (49.12%). Onset age was 30.00 (8.00, 74.50) months, and surgery age was 95.00 (50.00, 138.50) months. Focal to bilateral tonic-clonic seizures (42/57; 73.68%) and epileptic spasms (13/57; 22.81%) were common seizure types. Cranial MRI was positive in 34 patients (59.65%), mainly manifested as abnormal cortical gyri/sulci morphology (17/57; 29.82%). In 43 patients accepted PET-CT, hypometabolic sites were detected in 40 (93.02%), and complete agreement between PET/MRI fusion results and actual lesion sites was noted in 40 (93.02%). FCD type I was noted in 16 patients (28.07%), type II in 39 (68.42%), and type III in 2 (3.51%). By December 2023, 44 (77.19%) had Engel grading I, 4 (7.02%) had grading II, 4 (7.02%) had grading III, and 5 (8.77%) had grading IV. Children with good prognosis (Engel grading I+II) and those with poor prognosis (Engel grading III+IV) showed significant differences in terms of time from first seizure to surgery, positive/negative MRI, and regularity of postoperative ASMs ( P<0.05). Conclusions:Focal to bilateral tonic-clonic seizure is the most common seizure type in patients with epilepsy caused by FCD, and abnormal cortical gyri/sulci morphology is the most common MRI manifestation; PET/MRI fusion imaging is superior to PET-CT or MRI in identifying epileptogenic foci. Poor seizure control can be noted in patients with long onset time to surgery, with negative cranial MRI results, or with irregular postoperative ASMs.

Objective:To explore the clinical and genetic characteristics of asparagine synthase deficiency.Methods:Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed.Results:All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor.Conclusions:Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

OBJECTIVE: To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome. METHODS: The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents. RESULTS: Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c.4015C>T (exon 17) and c.5050G>A (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c.6161A>C (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient' s clinical phenotype. CONCLUSION The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.
CHARGE Syndrome/genetics* ; DNA Helicases/genetics* ; DNA-Binding Proteins/genetics* ; Genetic Testing ; Heterozygote ; Humans ; Mutation ; Phenotype ; Whole Exome Sequencing

Objective:To explore the clinical and genetic characteristics of a case of early-onset epileptic encephalopathy caused by the UBA5 gene mutation and to review relevant literatures. Methods:The clinical characte-ristics and genetic data of a child with the UBA5 gene mutation in the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University in June 2020 were retrospectively analyzed.Clinical characteristics and gene variation characteristics of the disease were reviewed in the domestic and foreign databases. Results:(1) The female patient presented infantile spasms at the age of 4 months.Electroencephalogram(EEG) suggested hypsarrhythmia and she was not responsive to a variety of anti-epileptic drugs.Besides, the patient showed severe cognitive and motor development delay, hypotonia, and microcephaly.The results of whole exome sequencing showed that the compound heterozygous mutation of UBA5 gene: exon 3 c. 214C>T (p.R72C) and exon 9 c. 844_c.845 insA (p.Y282Xfs*1), her father carries c. 214C>T mutation and her mother carries c. 844_c.845 INSA mutation.(2) To December 2020, a total of 15 cases of early-onset epileptic encephalopathy caused by the UBA5 gene mutation have been reported abroad.The main clinical manifestations were uncontrollable spasms, abnormal EEG findings, hypotonia, severe cognitive and movement disorders, microcephaly, and brain atrophy.A total of 11 mutation sites of the UBA5 gene were found, all belonging to the autosomal recessive inheritance, of which c. 1111G>A was the most common. Conclusions:The UBA5 gene mutation can lead to early-onset epileptic encephalopathy, which belongs to the autosomal recessive inheritance.It is featured by the early onset, uncontrollable seizures and poor long-term prognosis.

Congenital disorder of glycosylation (CDG) is a group of genetic metabolic diseases involving multiple organs. A case of CDG caused by SLC35A2 gene mutation was diagnosed. The clinical characteristics included spasms, developmental retardation and multiple malformations. Video-electroencephalogram showed dysrhythmia. A de novo heterozygous missense mutation of SLC35A2 gene was detected by whole exome sequencing: c.844G>A (p.Gly282Arg). It was predicted to be likely pathogenic according to American College of Medical Genetics and Genomics guidelines which had not been reported in China.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

Objective:To summarize the clinical characteristics of drug-resistant epilepsy (DRE) in children and to analyze the efficacy of lamotrigine (LTG) add-on therapy for DRE in children of different seizure type, syndrome and etiological category.Methods:All cases of DRE patients treated with LTG or other antiseizure medication (ASM) adjunctive therapy in the Third Affiliated Hospital of Zhengzhou University from May 2019 to April 2020 were collected.The LTG add-on therapy group was treated with LTG add-on therapy, and the control group was treated with other ASM add-on therapy.The therapeutic effects of the two groups were compared.Results:A total of 134 cases meeting the requirement of research were collected, including 98 cases in the LTG add-on therapy group and 36 cases in the control group.For seizure of focal onset and unknown origin, there was statistical difference in efficacy between the LTG add-on therapy group and the control group ( Z=-2.48、-2.11, P<0.05), but for generalized DRE in children, there was no statistical difference in efficacy between the two groups ( Z=-0.39, P>0.05). There was a significantly statistical difference in curative effect between the LTG add-on therapy group and the control group for childhood DRE which could not be classified as any epileptic syndrome ( Z=-3.99, P<0.01), but there was no statistical difference in efficacy between the two groups for West syndrome and benign epilepsy accompanied by central temporal spikes ( Z=-0.94、-1.22, P>0.05). For childhood intractable epilepsy with unknown etiology, there was statistical difference in efficacy between the LTG add-on therapy group and the control group ( Z=-1.96, P<0.05), and for childhood intractable epilepsy with structural etiology, there was significantly statistical difference in efficacy between the two groups ( Z=-3.07, P<0.01), but there was no statistical difference in the efficacy for childhood intractable epilepsy with genetic etiology between the two groups ( Z=-1.02, P>0.05). Conclusion:The efficacy of LTG add-on therapy is significantly better than others for childhood DRE with seizure of focal onset or unknown origin, childhood DRE unclassified to any syndrome, and childhood DRE with structural etiology and unknown origin, especially with structural etiology.

Objective:To summarize the clinical features and PLGL gene variation characteristics of children with CHIME syndrome. Methods:The medical records of one patient who was diagnosed with CHIME syndrome in the Third Affiliated Hospital of Zhengzhou University in October 2018 were analyzed.Foreign and domestic databases were searched with " CHIME syndrome or PIGL gene" as the keywords, so as to review clinical features of CHIME syndrome and PIGL gene variation characteristics. Results:(1) The boy, 1 year old and 3 months, developed seizures at the age of 7 months, when he received rehabilitation due to developmental delay.Physical examination showed that the boy had facial dysmorphisms, including high forehead, ocular hypertelorism, low and flat nasal root, broad nose tip, full lips, overfolded helices, cleft palate, developmental delay, dry skin, erythematous papular rash on the neck, and indirect inguinal hernia. Conductive deafness was revealed by the hearing test and retinal defect was found in fundus examination.Whole exome sequencing test identified PIGL(NM_004278)gene compound hybrid variation.The frameshift variation c. 26delT was present in one allele, combined with a synonymous variation c. 333C>T in the opposite allele.(2) A total of 9 CHIME syndrome patients were retrieved from the databases.No cases were reported in China.All 9 patients had craniofacial dysmorphism, epilepsy, conductive deafness, development delay and retinal defect.Eight patients had ichthyosiform skin, 6 patients had congenital heart disease and 4 patients had renal malformation.There were 6 different kinds of PIGL gene variations in patients, including 7 missense variants, 4 frameshift variants, 3 deletion variants, 2 nonsense variants, 1 splice variant, and 1 synonymous variant. All of the missense variants were c. 500T>C (p.Leu167Pro), which was the most common site. Conclusions:CHIME syndrome is mainly manifested by nervous system and dermal system abnormalities, and often involves multiple systems. PIGL gene variation is the cause of CHIME syndrome, and c. 500T>C (p.Leu167Pro) is the most common site.