Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors.

Introduction: Low-grade epilepsy-associated tumors are the second most common histopathological diagnoses in cases of drug-resistant focal epilepsy. However, the connection between neuroimaging features and genetic alterations in these tumors is unclear, prompting an investigation into genotype-relevant neuroimaging characteristics.

Methods: This study retrospectively analyzed neuroimaging and surgical specimens from 46 epilepsy patients with low-grade epilepsy-associated neuroepithelial tumors that had genetic mutations identified through panel sequencing to investigate their relationship to genotypes.

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls.

Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia.

Abnormality in GABAergic postsynaptic transmission associated with anxiety in mice with an mutation.

The homozygous () mouse, which shows hearing impairment, also exhibits anxiety accompanied by a reduction in cortical parvalbumin (PV)-positive GABAergic interneurons. Recently, a mutation in splicing factor Ser/Arg repetitive matrix 4 (Srrm4) was found in mice. However, the cellular consequences of the mutation for anxiety remain unknown.

Exploring the genetic diversity of the Japanese population: Insights from a large-scale whole genome sequencing analysis.

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. We analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective from the genomic data of 9,287 samples obtained by high-coverage whole-genome sequencing (WGS) by the National Center Biobank Network. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo).

LOX-1 mediates inflammatory activation of microglial cells through the p38-MAPK/NF-κB pathways under hypoxic-ischemic conditions.

Background: Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy (nHIE) model brain.

Duplication within two regions distal to MECP2: clinical similarity with MECP2 duplication syndrome.

Background: X-linked methyl-CpG-binding protein 2 (MECP2) duplication syndrome is prevalent in approximately 1% of X-linked intellectual disabilities. Accumulating evidence has suggested that MECP2 is the causative gene of MECP2 duplication syndrome. We report a case of a 17-year-old boy with a 1.

5-HT Receptor Agonist Treatment Partially Ameliorates Rett Syndrome Phenotypes in -Null Mice by Rescuing Impairment of Neuron Transmission and the CREB/BDNF Signaling Pathway.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the gene that encodes methyl CpG-binding protein 2 (MECP2) and is characterized by the loss of acquired motor and language skills, stereotypic movements, respiratory abnormalities and autistic features. There has been no effective treatment for this disorder until now. In this study, we used a -null (KO) mouse model of RTT to investigate whether repeated intraperitoneal treatment with the 5-HT receptor agonist tandospirone could improve the RTT phenotype.

National Center Biobank Network.

There are six national centers (6NCs) for advanced and specialized medicine in Japan that conduct basic and clinical research on major diseases that have a substantial impact on national health. Disease-specific bioresources and information collected by each NC are stored in a separate biobank. The National Center Biobank Network (NCBN) was established in 2011 and coordinates the biobanks and researchers of the 6NCs via an open-access database (Catalogue Database: http://www2.

Long-term changes in electroencephalogram findings in a girl with a nonsense SMC1A variant: A case report.

Introduction: Pathogenic truncating variants in SMC1A, which is located on chromosome Xp11.2, are known to cause infantile-onset epilepsy and severe intellectual disability in girls. Several studies have reported a correlation between SMC1A truncations and seizure clustering; however, the associated electroencephalogram (EEG) patterns remain largely unknown.

A familial 2p14 microdeletion disrupting actin-related protein 2 and Ras-related protein Rab-1A genes with intellectual disability and language impairment.

Microdeletions encompassing the 2p14 region have been reported to cause a novel microdeletion syndrome, characterised by mild intellectual disability (ID) and language impairment (LI), usually showing no congenital malformations or severe dysmorphisms. Actin-related protein 2 (ACTR2) and Ras-related protein Rab-1A (RAB1A) genes present in this region have been suggested to be associated with ID and/or LI pathogenesis on the basis of a few singleton cases with 2p14 microdeletions, although the effects of other deleted genes could not be ruled out. Here, we describe the clinical and molecular cytogenetic characterisation of a three-generation Japanese family comprising six individuals carrying a 144-kb microdeletion at the 2p14 locus, which disrupted two genes, ACTR2 and RAB1A, and co-segregated with ID and LI.

Myoclonic Epilepsy with Ragged-red Fibers with Intranuclear Inclusions.

We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions.

Linear cortical cystic lesions: Characteristic MR findings in MELAS patients.

Background: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a progressive neurodegenerative disorder with stroke-like lesions. The common MRI findings are gyral swelling and high signal intensity on T2WI/FLAIR images crossing the vascular territories. We have observed a linear cystic lesion and a laminar necrosis in the affected cortices of MELAS patients.

Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Related Microglial Activation in Neonatal Hypoxic-Ischemic Encephalopathy: Morphologic Consideration.

Neonatal hypoxic-ischemic encephalopathy (nHIE) is a major neonatal brain injury. Despite therapeutic hypothermia, mortality and sequelae remain severe. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with the pathophysiology of nHIE.

Estimation of the Number of Patients With Mitochondrial Diseases: A Descriptive Study Using a Nationwide Database in Japan.

Background: To provide a better healthcare system for patients with mitochondrial diseases, it is important to understand the basic epidemiology of these conditions, including the number of patients affected. However, little information about them has appeared in Japan to date.

Methods: To gather data of patients with mitochondrial diseases, we estimated the number of patients with mitochondrial diseases from April 2018 through March 2019 using a national Japanese health care claims database, the National Database (NDB).

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.

Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy.

Whole genome sequencing of 45 Japanese patients with intellectual disability.

Intellectual disability (ID) is characterized by significant limitations in both intellectual functioning and adaptive behaviors, originating before the age of 18 years. However, the genetic etiologies of ID are still incompletely elucidated due to the wide range of clinical and genetic heterogeneity. Whole genome sequencing (WGS) has been applied as a single-step clinical diagnostic tool for ID because it detects genetic variations with a wide range of resolution from single nucleotide variants (SNVs) to structural variants (SVs).

Nervonic acid level in cerebrospinal fluid is a candidate biomarker for depressive and manic symptoms: A pilot study.

Objective: Our previous metabolomics study showed that the plasma nervonic acid levels were higher in patients with major depressive disorder (MDD) than those in healthy controls and patients with bipolar disorder (BD). To examine whether the nervonic acid levels differ in the central nervous system, we investigated the levels in the cerebrospinal fluid (CSF) of patients with MDD, BD, and healthy controls.

Methods: Nervonic acid levels in CSF were measured by gas chromatography time-of-flight mass spectrometry.

Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility.

The Ihara epileptic rat (IER) is a mutant model with limbic-like seizures whose pathology and causative gene remain elusive. In this report, via linkage analysis, we identified Down syndrome cell adhesion molecule-like 1(Dscaml1) as the responsible gene for IER. A single base mutation in Dscaml1 causes abnormal splicing, leading to lack of DSCAML1.

Hyperglycemic Crisis in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS).

Background: Diabetes mellitus is the most commonly encountered endocrinopathy in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which manifests as multisystemic organ failure. Whether the management of diabetes mellitus in MELAS requires special consideration is not fully clarified.

Methods: In this single-center study, we retrospectively reviewed the medical records of patients with MELAS to elucidate the clinical characteristics of MELAS-associated diabetes mellitus.

Chemical reversal of abnormalities in cells carrying mitochondrial DNA mutations.

Mitochondrial DNA (mtDNA) mutations are the major cause of mitochondrial diseases. Cells harboring disease-related mtDNA mutations exhibit various phenotypic abnormalities, such as reduced respiration and elevated lactic acid production. Induced pluripotent stem cell (iPSC) lines derived from patients with mitochondrial disease, with high proportions of mutated mtDNA, exhibit defects in maturation into neurons or cardiomyocytes.

DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees.

Investigating DNA Methylation of SHATI/NAT8L Promoter Sites in Blood of Unmedicated Patients with Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most common psychiatric diseases. However, early detection and diagnosis of MDD is difficult, largely because there is no known biomarker or objective diagnostic examination, and its diagnosis is instead based on a clinical interview. The aim of this study was to develop a novel diagnostic tool using DNA methylation as a blood biomarker.