ABSTRACT
This study aimed to identify characteristic proteins in infantile epileptic spasm syndrome (IESS) patients' plasma, offering insights into potential early diagnostic biomarkers and its underlying causes. Plasma samples were gathered from 60 patients with IESS and 40 healthy controls. Data-independent acquisition proteomic analysis was utilized to identify differentially expressed proteins (DEPs). These DEPs underwent functional annotation through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Gene set enrichment analysis (GSEA) was employed for both GO (GSEA-GO) and KEGG (GSEA-KEGG) analyses to examine the gene expression profiles. Receiver operating characteristic (ROC) curves assessed biomarkers' discriminatory capacity. A total of 124 DEPs were identified in IESS patients' plasma, mainly linked to pathways, encompassing chemokines, cytokines, and oxidative detoxification. GSEA-GO and GSEA-KEGG analyses indicated significant enrichment of genes associated with cell migration, focal adhesion, and phagosome pathways. ROC curve analysis demonstrated that the combination of PRSS1 and ACTB, PRSS3, ACTB, and PRSS1 alone exhibited AUC values exceeding 0.7. This study elucidated the significant contribution of cytokines, chemokines, oxidative detoxification, and phagosomes to the IESS pathogenesis. The combination of PRSS1 and ACTB holds promise as biomarkers for the early diagnosis of IESS.
ABSTRACT
Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.
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OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
ABSTRACT
Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.
Subject(s)
COVID-19 , Epilepsy , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Consensus , East Asian People , Epilepsy/complications , Epilepsy/epidemiology , VaccinationABSTRACT
BACKGROUND: White-Sutton syndrome is an autosomal dominant neurodevelopmental disorder caused by heterozygous mutation in POGZ (Pogo Transposable Element Derived with ZNF Domain). This syndrome is characterized by delayed psychomotor development apparent in infancy and abnormal facial features. To date, 80 cases have been reported in the literature; however, the phenotypic characterizations remain incomplete. CASE PRESENTATION: We herein describe a 2-year-old girl harboring a novel frameshift de novo POGZ variant: c.2746del (p.Thr916ProfsTer12). This patient presented with multisystem abnormalities affecting the digestive tract and neurological functioning, as well as congenital heart disease, which involved an atrial septal defect (18 × 23 × 22 mm) with pulmonary arterial hypertension (42 mmHg). The relationship between congenital heart disease and White-Sutton syndrome as described in both the GeneReview and OMIM databases (#616,364) remains unclear. A review of the current literature revealed 18 cases of White-Sutton syndrome with POGZ variants and congenital heart disease, and we summarize their clinical features in this study. CONCLUSIONS: Our findings based on the present case and those in the literature indicate a relationship between POGZ mutation and congenital heart disease.
Subject(s)
Abnormalities, Multiple , Heart Defects, Congenital , Intellectual Disability , Female , Humans , Child, Preschool , Heart Defects, Congenital/complications , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/genetics , Intellectual Disability/genetics , Mutation , Frameshift Mutation , Abnormalities, Multiple/genetics , PhenotypeABSTRACT
Tuberous sclerosis complex (TSC) is a multi-system genetic disorder. Most patients have germline mutations in TSC1 or TSC2 but, 10%-15% patients do not have TSC1/TSC2 mutations detected on routine clinical genetic testing. We investigated the contribution of low-level mosaic TSC1/TSC2 mutations in unsolved sporadic patients and families with TSC. Thirty-one sporadic TSC patients negative on routine testing and eight families with suspected parental mosaicism were sequenced using deep panel sequencing followed by droplet digital polymerase chain reaction. Pathogenic variants were found in 22/31 (71%) unsolved sporadic patients, 16 were mosaic (median variant allele fraction [VAF] 6.8% in blood) and 6 had missed germline mutations. Parental mosaicism was detected in 5/8 families (median VAF 1% in blood). Clinical testing laboratories typically only report pathogenic variants with allele fractions above 10%. Our findings highlight the critical need to change laboratory practice by implementing higher sensitivity assays to improve diagnostic yield, inform patient management and guide reproductive counseling.
Subject(s)
Tuberous Sclerosis , Humans , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/genetics , Tuberous Sclerosis/pathology , Tuberous Sclerosis Complex 2 Protein/genetics , Tuberous Sclerosis Complex 1 Protein/genetics , Tumor Suppressor Proteins/genetics , Mosaicism , MutationABSTRACT
The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling. We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed. Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length <25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associated with epilepsy, developmental retardation and congenital abnormalities. Four particular 16p11.2 deletions and two 15q11.2 deletions were considered to be susceptibility factors contributing to neurodevelopmental disorders associated with epilepsy. The diagnostic yield was 75.0% in patients with seizure onset during the first postnatal month, and gradually decreased in patients with seizure onset at a later age. Forty-two patients (13.1%) were found to be specifically treatable for the underlying genetic cause identified by genome sequencing. Three of them received corresponding targeted therapies and demonstrated favourable prognoses. Genome sequencing provides complete genetic diagnosis, thus enabling individualized treatment and genetic counselling for the parents of the patients. Genome sequencing is expected to become the first choice of methods for genetic testing of patients with epilepsy.
Subject(s)
DNA Copy Number Variations/genetics , Epilepsy/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Adolescent , Asian People/genetics , Child , Child, Preschool , Female , Genetic Testing/methods , Genome-Wide Association Study , Genotype , Humans , Infant , Infant, Newborn , MaleABSTRACT
Background: Effectively reducing the expression of certain aversive memories (fear or trauma memories) with extinction training is generally viewed to be therapeutically important. A deeper understanding of the biological basis for a more effective extinction process is also of high scientific importance. Methods: Our study involved intraventricular injection or local injection into the dorsal dentate gyrus of anti-neuregulin 1 antibodies (anti-NRG1) before fear extinction training, followed by testing the expression of fear memory 24 hours afterward or 9 days later. We used local injection of chemogenetic or optogenetic viruses into the dorsal dentate gyrus to manipulate the activity of the dorsal dentate gyrus and test the expression of fear memory. We also examined the effect of deep brain stimulation in the dorsal dentate gyrus on the expression of fear memory. Results: Mice that received intraventricular injection with anti-NRG1 antibodies exhibited lower expression of fear memory and increased density of activated excitatory neurons in the dorsal dentate gyrus. Injection of anti-NRG1 antibodies directly into the dorsal dentate gyrus also led to lower expression of fear memory and more activated neurons in the dorsal dentate gyrus. Inhibiting the activity of dorsal dentate gyrus excitatory neurons using an inhibitory designer receptor exclusively activated by designer drugs (DREADD) eliminated the effects of the anti-NRG1 antibodies. Enhancing the activity of the dorsal dentate gyrus with an excitatory DREADD or optogenetic stimulation resulted in lower expression of fear memory in mice that did not receive infusion of anti-NRG1 antibodies. Deep brain stimulation in the dorsal dentate gyrus effectively suppressed expression of fear memory, both during and after fear extinction training. Limitations: The mechanism for the contribution of the dorsal dentate gyrus to the expression of fear memory needs further exploration. Conclusion: Activation of the dorsal dentate gyrus may play an important role in modulating the expression of fear memory; its potential use in fear memory extinction is worthy of further exploration.
Subject(s)
Dentate Gyrus/physiology , Extinction, Psychological , Fear , Memory , Animals , Dentate Gyrus/cytology , Male , Mice , NeuronsABSTRACT
Compressed Sensing (CS) and parallel imaging are two promising techniques that accelerate the MRI acquisition process. Combining these two techniques is of great interest due to the complementary information used in each. In this study, we proposed a novel reconstruction framework that effectively combined compressed sensing and nonlinear parallel imaging technique for dynamic cardiac imaging. Specifically, the proposed method decouples the reconstruction process into two sequential steps: In the first step, a series of aliased dynamic images were reconstructed from the highly undersampled k-space data using compressed sensing; In the second step, nonlinear parallel imaging technique, i.e. nonlinear GRAPPA, was utilized to reconstruct the original dynamic images from the reconstructed k-space data obtained from the first step. In addition, we also proposed a tailored k-space down-sampling scheme that satisfies both the incoherent undersampling requirement for CS and the structured undersampling requirement for nonlinear parallel imaging. The proposed method was validated using four in vivo experiments of dynamic cardiac cine MRI with retrospective undersampling. Experimental results showed that the proposed method is superior at reducing aliasing artifacts and preserving the spatial details and temporal variations, compared with the competing k-t FOCUSS and k-t FOCUSS with sensitivity encoding methods, with the same numbers of measurements.
Subject(s)
Cardiovascular Diseases/diagnostic imaging , Data Compression/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging, Cine/methods , Artifacts , Datasets as Topic , Humans , Image Enhancement/methodsABSTRACT
Infantile hypertonic myofibrillar myopathy is characterized by the rapid development of rigid muscles and respiratory insufficiency soon after birth, with very high mortality. It is extremely rare, and only a few cases having been reported until now. Here we report four Chinese infants with fatal neuromuscular disorders characterized by abdominal and trunk skeletal muscle stiffness and rapid respiratory insufficiency progression. Electromyograms showed increased insertion activities and profuse fibrillation potentials with complex repetitive discharges. Immunohistochemistry staining of muscle biopsies showed accumulations of desmin in the myocytes. Powdery Z-bands with dense granules across sarcomeres were observed in muscle fibers using electron microscopy. All patients carry a homozygous c.3G>A mutation in the CRYAB gene, which resulted in the loss of the initiating methionine and the absence of protein. This study's findings help further understand the disease and highlight a founder mutation in the Chinese population.
Subject(s)
Muscle, Skeletal , Myopathies, Structural, Congenital/genetics , alpha-Crystallin B Chain/genetics , China , Electromyography , Fatal Outcome , Humans , Infant , Magnetic Resonance Imaging , Male , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Myopathies, Structural, Congenital/pathology , Myopathies, Structural, Congenital/physiopathologyABSTRACT
BACKGROUND: Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions. METHODS: This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei. RESULTS: The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods. CONCLUSION: Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.
Subject(s)
COVID-19/epidemiology , Infectious Disease Incubation Period , Adolescent , Adult , Aged , COVID-19/prevention & control , Child , China/epidemiology , Female , Geography , Humans , Male , Middle Aged , Quarantine , Retrospective Studies , SARS-CoV-2 , Young AdultABSTRACT
INTRODUCTION: Stereoelectroencephalography (SEEG) refers to a commonly used diagnostic procedure to localise and define the epileptogenic zone of refractory focal epilepsies, by means of minimally invasive operation techniques without large craniotomies. OBJECTIVE: This study aimed to investigate the influence of different registration methods on the accuracy of SEEG electrode implantation under neuronavigation for paediatric patients with refractory epilepsy. METHODS: The clinical data of 18 paediatric patients with refractory epilepsy were retrospectively analysed. The SEEG electrodes were implanted under optical neuronavigation while the patients were in the prone position. Patients were divided into two groups on the basis of the surface-based registration of MR scan method and refined anatomy-based registration of CT scan. Registration time, accuracy, and the differences between electrode placement and preoperative planned position were analysed. RESULTS: Thirty-six electrodes in 7 patients were placed under surface-based registration of MR scan, and 45 electrodes in 11 patients were placed under refined anatomy-based registration of CT scan. The registration time of surface-based registration of MR scan and refined anatomy-based registration of CT scan was 45 ± 12 min and 10 ± 4 min. In addition, the mean registration error, the error of insertion point, and target error were 3.6 ± 0.7 mm, 2.7 ± 0.7 mm, and 3.1 ± 0.5 mm in the surface-based registration of MR scan group, and 1.1 ± 0.3 mm, 1.5 ± 0.5 mm, and 2.2 ± 0.6 mm in the refined anatomy-based registration of CT scan group. The differences between the two registration methods were statistically significant. CONCLUSIONS: The refined anatomy-based registration of CT scan method can improve the registration efficiency and electrode placement accuracy, and thereby can be considered as the preferred registration method in the application of SEEG electrode implantation under neuronavigation for treatment of paediatric intractable epilepsy.
Subject(s)
Electrodes, Implanted/standards , Magnetic Resonance Imaging/standards , Neuronavigation/standards , Prone Position , Stereotaxic Techniques/standards , Tomography, X-Ray Computed/standards , Adolescent , Child , Child, Preschool , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/surgery , Electroencephalography/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Neuronavigation/methods , Prone Position/physiology , Retrospective Studies , Tomography, X-Ray Computed/methodsABSTRACT
Electroencephalogram (EEG) has been an important tool for scientists to study epilepsy and evaluate the treatment of epilepsy for half a century, since epilepsy seizures are caused by the diffusion of excessive discharge of brain neurons. This paper reviews the clinical application of scalp EEG in the treatment of intractable epilepsy with vagus nerve stimulation (VNS) in the past 30 years. It mainly introduces the prediction of the therapeutic effect of VNS on intractable epilepsy based on EEG characteristics and the effect of VNS on EEG of patients with intractable epilepsy, and expounds some therapeutic mechanisms of VNS. For predicting the efficacy of VNS based on EEG characteristics, EEG characteristics such as epileptiform discharge, polarity of slow cortical potential changes, changes of EEG symmetry level and changes of EEG power spectrum are described. In view of the influence of VNS treatment on patients' EEG characteristics, the change of epileptiform discharge, power spectrum, synchrony, brain network and amplitude of event-related potential P300 are described. Although no representative EEG markers have been identified for clinical promotion, this review paves the way for prospective studies of larger patient populations in the future to better apply EEG to the clinical treatment of VNS, and provides ideas for predicting VNS efficacy, assessing VNS efficacy, and understanding VNS treatment mechanisms, with broad medical and scientific implications.
Subject(s)
Drug Resistant Epilepsy , Vagus Nerve Stimulation , Electroencephalography , Humans , Prospective Studies , Scalp , Treatment OutcomeABSTRACT
Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by SLC7A7 gene mutation and often involves severe lesions in multiple systems. Lung involvement is frequently seen in children with LPI and such children tend to have a poor prognosis. This article summarizes the clinical manifestations and gene mutation characteristics of three children diagnosed with LPI by SLC7A7 gene analysis. All three children had the manifestations of aversion to protein-rich food after weaning, delayed development, anemia, hepatosplenomegaly, and osteoporosis, as well as an increase in orotic acid in urine. In addition, interstitial pneumonia and diffuse pulmonary interstitial lesions were observed in two children. SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A. After a definite diagnosis was made, all three children were given a low-protein diet and oral administration of citrulline [100 mg/(kg.d)], iron protein succinylate [4 mg/(kg.d)], calcium and zinc gluconates oral solution (10â mL/day) and vitamin D (400â IU/day). In addition, patient 3 was given prednisone acetate (5â mg/day). The children had varying degrees of improvement in symptoms and signs. It is hard to distinguish LPI from urea cycle disorder due to the features of amino acid and organic acid metabolism in LPI, and SLC7A7 gene analysis is the basis for a definite diagnosis of LPI.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Fusion Regulatory Protein 1, Light Chains/genetics , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Transport System y+L , Child , Citrulline , Humans , Lysine , MutationSubject(s)
Epilepsy , Asian People/genetics , Child , China , Epilepsy/genetics , Humans , Exome SequencingABSTRACT
To explore the relationship between NF2 promoter gene mutation and the risk of medulloblastomas (MBs). We collected tissues from 16 MB patients and 7 age-matched non-MB controls. Gene sequencing, qPCR (real-time quantitative polymerase chain reaction), IHC (immunohistochemistry), and WB (Western blot) were used to analyze the changes in the NF2 gene sequence and expression between patients and controls. We found that NF2 promoter gene mutations occurred in MB patients. The NF2 mRNA expression was higher in the controls than in patients (p = 0.03 < 0.05); however, the results of IHC and WB demonstrated that the NF2 protein expression was significantly higher in patients than in the controls (IHC: p = 0.0001; WB: p = 0.01). There was no significant difference in the CRL4 mRNA and protein levels. In addition, NF2 protein was mainly expressed in the nucleus in MB patients, while the NF2 protein was mainly expressed in the cytoplasm in the controls. NF2 promoter mutations exist in MB patients. NF2 mRNA expression was higher in controls than patients; whereas NF2 protein level was higher in patients than in controls.
Subject(s)
Brain Neoplasms/genetics , Genetic Predisposition to Disease , Medulloblastoma/genetics , Mutation , Neurofibromin 2/genetics , Promoter Regions, Genetic , Adolescent , Adult , Brain/metabolism , Brain/pathology , Brain/surgery , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Carrier Proteins/metabolism , Cell Nucleus/metabolism , Cell Nucleus/pathology , Child , Child, Preschool , Cytoplasm/metabolism , Cytoplasm/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Male , Medulloblastoma/metabolism , Medulloblastoma/pathology , Medulloblastoma/surgery , Neurofibromin 2/metabolism , Protein Serine-Threonine Kinases , RNA, Messenger/metabolism , Ubiquitin-Protein LigasesABSTRACT
OBJECTIVE: To analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A (CPT1A) deficiency. METHODS: Clinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPT1A gene were analyzed by PCR and Sanger sequencing. RESULTS: Analysis showed that the patient carried compound heterozygous mutations c.1787T>C and c.2201T>C of the CPT1A gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function. CONCLUSION: Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c.1787T>C and c.2201T>C mutations of the CPT1A gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.
Subject(s)
Carnitine O-Palmitoyltransferase/deficiency , Hypoglycemia/genetics , Lipid Metabolism, Inborn Errors/genetics , Base Sequence , Carnitine O-Palmitoyltransferase/genetics , Exons , Female , Humans , Hypoglycemia/enzymology , Infant , Lipid Metabolism, Inborn Errors/enzymology , Male , Molecular Sequence Data , Point Mutation , PregnancyABSTRACT
Infantile spasm (IS) syndrome is an age-related epileptic encephalopathy that occurs in children. The purpose of this study was to investigate regional homogeneity (ReHo) changes in IS patients. Resting-state fMRI was performed on 11 patients with IS, along with 35 age- and sex-matched healthy subjects. Group comparisons between the two groups demonstrate that the pattern of regional synchronization synchronization in IS patients is changed. Decreased ReHo values were found in default mode network, bilateral motor-related areas and left occipital gyrus of the patient group. Increased ReHo was found in regions of cingulum, cerebellum, supplementary motor area and brain deep nucleus, such as hippocampus, caudate, thalamus and insula. The significant differences might indicate that epileptic action have some injurious effects on the motor, executive and cognitive related regions. In addition, ReHo values of left precuneus and right superior frontal gyrus were associated with the epilepsy duration in the IS group. The correlation results indicate that the involvement of these regions may be related to the seizure generation. Our results suggest that IS may have an injurious effect on the brain activation. The findings may shed new light on the understanding the neural mechanism of IS epilepsy.
Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Spasms, Infantile/diagnostic imaging , Brain/physiopathology , Case-Control Studies , Child, Preschool , Female , Humans , Infant , Male , Spasms, Infantile/physiopathologyABSTRACT
OBJECTIVE: To investigate the changes in brain injury after the induction chemotherapy in children with acute lymphoblastic leukemia (ALL) by cranial MRI. METHODS: The clinical data and cranial MRI results of 62 children with ALL who were hospitalized from March 2014 to June 2015 were analyzed retrospectively. RESULTS: Before chemotherapy, MRI showed bone marrow infiltration of the skull in 33 patients (53%); the children with WBC<20×10(9)/Lhad a significantly lower incidence rate of bone marrow infiltration of the skull than those with WBC≥20×10(9)/L (16 patients/42% vs 17 patients/71%; P<0.05), and the high-risk group had a significantly higher incidence rate of bone marrow infiltration of the skull than the non-high-risk group (71% vs 44%; P<0.05). Before chemotherapy, there were 4 cases (7%) of brain atrophy, and 2 cases (3%) of abnormal signals in the sensory conduction bundle. MRI reexamination in 28 patients after 3 months of chemotherapy showed 3 new cases (11%) of brain atrophy and 1 aggravated case of brain atrophy. CONCLUSIONS: The children with ALL have bone marrow infiltration of the skull, brain atrophy, and abnormal signals in the sensory conduction bundle before chemotherapy, especially bone marrow infiltration of the skull, and some changes in brain injury disappear after treatment.
Subject(s)
Brain/drug effects , Induction Chemotherapy/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Bone Marrow/pathology , Brain/pathology , Child , Child, Preschool , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Retrospective Studies , Skull/pathologyABSTRACT
Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world.