Phenotypic and genotypic analysis of a patient with Miyoshi myopathy caused by truncated protein.

Dysferlin protein deficiency can cause neuromuscular dysfunction, resulting in autosomal recessive dysferlinopathy, which is caused by DYSF gene mutation. Dysferlin proteins belongs to the Ferlin1-like protein family and are associated with muscle membrane repair and regeneration. In China, pathogenic mutations of the protein often result in two clinical phenotypes of Miyoshi muscular or limb band muscular dystrophy type 2B.

SCAF4 variants are associated with epilepsy with neurodevelopmental disorders.

Aims: The genetic causes of epilepsy with unknown etiology in most patients remain unknown. The aim of this study was to elucidate the phenotype of SCAF4-related epilepsy.

Methods: Trio-based whole-exome sequencing was performed in patients with epilepsy.

Perampanel and lacosamide monotherapy in pediatric patients with newly diagnosed focal epilepsy: A prospective study evaluating efficacy, tolerability, and behavior.

Purpose: Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy.

Therapeutic Drug Monitoring of Perampanel in Children With Refractory Epilepsy: Focus on Influencing Factors on the Free-Perampanel Concentration.

Background: This study aimed to assess the effect of perampanel dose, age, sex, and antiseizure medication cotherapy on steady-state free-perampanel concentration in children with refractory epilepsy, as well as the relationship between inflammation and the pharmacokinetics of perampanel.

Methods: This prospective study in China included 87 children with refractory epilepsy treated with adjunctive perampanel therapy. Free and total perampanel concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry.

Treating mutation-related severe movement disorders with oxcarbazepine: a case report.

Background: variants have been found to be associated with epileptic encephalopathies, developmental delays (DDs), and movement disorders (MDs). Therapies for patients with variants vary. However, treatments for GNAO1-related diseases are still in their infancy.

Development and validation of a nomogram for the early prediction of drug resistance in children with epilepsy.

Background And Purpose: This study aimed to effectively identify children with drug-resistant epilepsy (DRE) in the early stage of epilepsy, and take personalized interventions, to improve patients' prognosis, reduce serious comorbidity, and save social resources. Herein, we developed and validated a nomogram prediction model for children with DRE.

Methods: The training set was patients with epilepsy who visited the Children's Hospital of Soochow University (Suzhou Industrial Park, Jiangsu Province, China) between January 2015 and December 2017.

Use of perampanel in children with refractory epilepsy of genetic aetiology.

Objective: Pathogenic mutations in refractory childhood epilepsy are being increasingly discovered. In this study, we analysed the efficacy and tolerability of perampanel as treatment for genetically-related refractory childhood epilepsy.

Methods: This prospective study, conducted in China, included 50 patients with refractory epilepsy of genetic aetiology, who were treated with adjunctive perampanel therapy.

CELSR3 variants are associated with febrile seizures and epilepsy with antecedent febrile seizures.

Aims: To identify novel pathogenic gene of febrile seizures (FS)/epilepsy with antecedent FS (EFS+).

Methods: The trio-based whole-exome sequencing was performed in a cohort of 462 cases with FS/EFS+. Silico programs, sequence alignment, and protein modeling were used to predict the damaging of variants.

Effectiveness and safety of perampanel in Chinese paediatric patients (2-14 years) with refractory epilepsy: a retrospective, observational study.

We report our clinical experience of the effectiveness and tolerability of adjunctive perampanel treatment in a Chinese paediatric population with refractory epilepsy. We also compare the effectiveness and tolerability of perampanel with or without concomitant oxcarbazepine or levetiracetam. This retrospective observational study was conducted from September 2019 to September 2020 in the paediatric neurology clinics of two tertiary hospitals in the Chinese mainland.

Trio exome sequencing identified a novel de novo WASF1 missense variant leading to recurrent site substitution in a Chinese patient with developmental delay, microcephaly, and early-onset seizures: A mutational hotspot p.Trp161 and literature review.

Background: Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, OMIM # 618707) is a newly described autosomal dominant condition caused by heterozygous de novo mutation in WASF1 gene. WASF1 is a key component of the WAVE regulatory complex (WRC) required for actin polymerization. So far, only 3 distinct truncating variants clustering at the WCA domain, 3 missense variants localized to the meander region and a copy number variant (CNV) of WASF1 have been identified among 11 NEDALVS cases previously reported.

A De Novo SEMA6B Variant in a Chinese Patient with Progressive Myoclonic Epilepsy-11 and Review of the Literature.

Progressive myoclonic epilepsy is a group of neurodegenerative diseases with complex clinical and genetic heterogeneity, which is associated with spontaneous or action-induced myoclonus and progressive neurodegeneration. Since 2020, 4 families with progressive myoclonic epilepsy-11 [OMIM#618876] have been reported with a very limited spectrum of SEMA6B pathogenic variants. In our study, whole-exome sequencing was used in a proband from a nonconsanguineous Chinese family presenting with growth retardation and recurrent atonic seizures.

De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene-disease relationship and variant classification: a case report.

Background: ATP1A2 gene mutation has been indicated to cause alternating hemiplegia of childhood (AHC); however, limited evidence supports this relationship so far.

Case Presentation: We reported two Chinese patients with de novo ATP1A2 variants (c.970G>A and c.

Systematic elucidation of the pharmacological mechanisms of Rhynchophylline for treating epilepsy via network pharmacology.

Abstact: BACKGROUND: Epilepsy, one of the most common neurological disorders, affects over 70 million people worldwide. Rhynchophylline displays a wide variety of pharmacologic actives. However, the pharmacologic effects of rhynchophylline and its mechanisms against epilepsy have not been systematically elucidated.

Proteinuria as a presenting sign of combined methylmalonic acidemia and homocysteinemia: case report.

Background: Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare.

Clinical and Molecular Characteristics of Two Chinese Children with Infantile Sandhoff Disease and Review of the Literature.

Infantile Sandhoff disease is an autosomal recessive inherited disease primarily characterized by cherry red spots in the retina, muscle weakness, seizure, truncal hypotonia, hyperacusis, developmental delay and regression. The pathogenic genetic defects of the HEXB gene, which encodes the β subunit of the hexosaminidase A (ɑβ) and hexosaminidase B (ββ) enzymes, cause deficiency of both the Hex A and Hex B enzymes, resulting in the deposition of GM2 ganglion glycerides in the lysosomes of the central nervous system and somatic cells. The aim of this study was to discover disease-causing variants of the HEXB gene in two Chinese families through the use of exome sequencing.

Myeloid-Related Protein 8/14 Participates in the Progression of Experimental Pneumococcal Meningitis by Augmentation of Inflammation.

It has been reported that myeloid-related protein 8/14 (MRP8/14) participates in the progression of inflammation after release from neutrophils and monocytes. This study aimed to clarify the mechanism(s) of the MRP8/14-augmented inflammatory response in mice with pneumococcal meningitis. Streptococcus pneumoniae (SP) meningitis was established by intracerebral injection of SP suspension.

ATP7B Mutation Detection and Pathogenicity Analysis: One Atypical Case of Wilson's Disease with Adrenocortical Insufficiency.

Wilson's disease (WD) is an autosomal recessive disorder caused by defective function of the copper-transporting ATP7B protein. Symptoms are typically related to the brain and liver, while endocrinologic abnormalities are rare. Here, we reported a 12-year-old female patient that was initially presented with unusual skin darkening and low serum level of adrenocorticotropic hormone and diagnosed as having adrenocortical insufficiency.

Dysregulation of zinc/lipid metabolism‑associated genes in the rat hippocampus and cerebral cortex in early adulthood following recurrent neonatal seizures.

Although it has been established that recurrent or prolonged clinical seizures during infancy may cause lifelong brain damage, the underlying molecular mechanism is still not well elucidated. The present study, to the best of our knowledge, is the first to investigate the expression of twenty zinc (Zn)/lipid metabolism‑associated genes in the hippocampus and cerebral cortex of rats following recurrent neonatal seizures. In the current study, 6‑day‑old Sprague‑Dawley rats were randomly divided into control (CONT) and recurrent neonatal seizure (RS) groups.

Activation of the TLR2-mediated downstream signaling pathways NF-κB and MAPK is responsible for B7-H3-augmented inflammatory response during S. pneumoniae infection.

It has been reported that B7-H3, a costimulatory protein, participates in the development and progression of experimental pneumococcal meningitis by amplifying the TLR2-mediated inflammatory response. This study attempted to clarify the pathway(s) of TLR2 signaling involved in B7-H3-augmented inflammatory response during S. pneumoniae infection.

B7-H3 Augments Inflammatory Responses and Exacerbates Brain Damage via Amplifying NF-κB p65 and MAPK p38 Activation during Experimental Pneumococcal Meningitis.

The costimulatory protein B7-H3 has been shown to play a contributory role in the development and progression of experimental pneumococcal meningitis by augmentation of the innate immunity-associated inflammatory response via a TLR2-dependent manner. This study aimed to clarify the component(s) of TLR2-mediated signal transduction pathways responsible for B7-H3-augmented inflammatory response and subsequent brain damage during experimental pneumococcal meningitis. Administration of B7-H3 did not augment expression of TLR2 and other TLR2 upstream components, but led to an enhanced formation of MyD88-IRAK immunocomplex in the brain of S.

Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.

The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed.

B7 homolog 3 aggravates brain injury in a murine model of -induced meningitis.

Despite the application of antibiotics, (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3.

Effect of topiramate on interleukin 6 expression in the hippocampus of amygdala-kindled epileptic rats.

The objective of this study was to analyze the changes in expression and the possible functions of interleukin-6 (IL-6) in electrical kindling of the basolateral amygdala (BLA) in epileptic rats. Bipolar electrodes were implanted into the BLA of Sprague-Dawley rats, and the rats were then subjected to chronic electrical stimulation through the electrodes to induce kindling. The seizure characteristics and behavioral changes of the rats were observed, and electroencephalograms were recorded during and following kindling.

Effects of B7-H3 on the inflammatory response and expression of MMP-9 in mice with pneumococcal meningitis.

B7-H3, a new member of the B7 superfamily, plays a key role in the regulation of T cell-mediated immune responses. Our previous work showed that B7-H3 strongly augmented both LPS- and bacterial lipoprotein-induced NF-κB activation and inflammatory response, and soluble B7-H3 was elevated in CSF and plasma of patients with bacterial meningitis. MMP-9 has been implicated in blood-brain barrier disruption, inflammation, and vasculitis during the pathogenesis of bacterial meningitis.