The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, leading to dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping offers potential by partially restoring dystrophin, though current therapies remain mutation specific with limited efficacy. To overcome those limitations, we developed brogidirsen, a dual-targeting ASO composed of two directly connected 12-mer sequences targeting exon 44 using phosphorodiamidate morpholino oligomers.

Paroxysmal delta waves of awake EEG in childhood adrenoleukodystrophy: Possible indicator of the hematopoietic stem cell therapy (HSCT).

Background: Childhood cerebral type of Adrenoleukodystrophy (CC-ALD) is fatal without hematopoietic stem cell transplantation (HSCT). We consider whether EEGs showing focal paroxysmal delta waves can be a candidate of early detector of the apparent ALD and HSCT therapy.

Methods: Twenty-two male children with ALD (5-16 years; 10.

[Taro Okamoto and Parkinson's Disease].

Taro Okamoto, a famous Japanese artist, theorist, and writer developed Parkinson's disease during the later years of life. Facial pareidolia associated with Parkinson's disease led to the idea of "Glass with Face." Color vision impairment and reduced contrast sensitivity affected the use of colors in his paintings, and the focus of his creative activities shifted from painting to ceramics and sculpture.

[Franz Joseph Haydn and Subcortical Vascular Encephalopathy].

Franz Joseph Haydn was a prominent musician in the late 1700s. Researchers have speculated that Haydn may have suffered from subcortical cerebrovascular disease. These interpretations, based on biographical and other sources, might be accurate.

A Retrospective Cohort Study of a Newly Proposed Criteria for Sporadic Creutzfeldt-Jakob Disease.

Background/objectives: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD.

History and Perspective of LAMP-2 Deficiency (Danon Disease).

Danon disease, an X-linked dominant vacuolar cardiomyopathy and skeletal myopathy, is caused by a primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). This disease is one of the autophagy-related muscle diseases. Male patients present with the triad of cardiomyopathy, myopathy, and intellectual disability, while female patients present with cardiomyopathy.

CGG/CCG Repeat Expansions in in Thai Patients With Oculopharyngodistal Myopathy.

Objectives: This study characterizes oculopharyngodistal myopathy in 4 Thai patients from 3 families with CGG/CCG repeat expansion in .

Methods: Repeat-primed PCR analyzed CGG/CCG repeat size in in 4 Thai patients suspected of oculopharyngodistal myopathy (OPDM). Clinical records were reviewed for clinicopathologic features.

GNE Myopathy: Genotype - Phenotype Correlation and Disease Progression in an Indian Cohort.

Introduction: GNE myopathy is a rare slowly progressive adult-onset distal myopathy with autosomal recessive inheritance. It has distinctive features of quadriceps sparing with preferential anterior tibial involvement. Most patients eventually become wheelchair bound by 10-20 years after onset.

Update on RYR1-related myopathies.

Purpose Of Review: RYR1-related myopathy (RYR1-RM) is a group of myopathies caused by mutations in the RYR1 gene, which encodes the ryanodine receptor 1 (RYR1). This review discusses recent advances in the clinical features, pathology, pathogenesis, and therapeutics of RYR1-RM.

Recent Findings: Although treatments such as salbutamol, pyridostigmine, and N-acetylcysteine have been explored as potential therapies for RYR1-RM, none have been conclusively proven to be effective.

Erroneous predictive coding across brain hierarchies in a non-human primate model of autism spectrum disorder.

In autism spectrum disorder (ASD), atypical sensory experiences are often associated with irregularities in predictive coding, which proposes that the brain creates hierarchical sensory models via a bidirectional process of predictions and prediction errors. However, it remains unclear how these irregularities manifest across different functional hierarchies in the brain. To address this, we study a marmoset model of ASD induced by valproic acid (VPA) treatment.

[Diagnosis of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis led by sarcoplasmic myxovirus resistance protein A expression on muscle pathology].

A 44-year-old woman with autism spectrum disorder developed bulbar symptoms and generalized muscle weakness 7 months before referral. Six months before, she was administered glucocorticoid for liver involvement. During the course, while she presented alopecia, skin ulcers, and poikiloderma, hyperCKemia was observed only twice.

[Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report].

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy.

Large phenotypic diversity by genotype in patients with GNE myopathy: 10 years after the establishment of a national registry in Japan.

Background: GNE myopathy is an ultra-rare autosomal recessive distal myopathy caused by pathogenic variants of the GNE gene, which encodes a key enzyme in sialic acid biosynthesis. The present study aimed to examine the long-term progression of GNE myopathy, genotype-phenotype correlations, and complications to provide useful information for predicting patient progression and designing clinical trials using a large collection of registry data over a 10-year period.

Methods: We analyzed 220 Japanese patients with GNE myopathy from a national registry in Japan.

Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Update of the 2012 guidelines.

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers.

Limb-Clasping Response in NMDA Receptor Palmitoylation-Deficient Mice.

Proper regulation of N-methyl-D-aspartate-type glutamate receptor (NMDA receptor) expression is responsible for excitatory synaptic functions in the mammalian brain. NMDA receptor dysfunction can cause various neuropsychiatric disorders and neurodegenerative diseases. Posttranslational protein S-palmitoylation, the covalent attachment of palmitic acid to intracellular cysteine residues via thioester bonds, occurs in the carboxyl terminus of GluN2B, which is the major regulatory NMDA receptor subunit.

[Neuropathology of Inflammatory and Autoimmune-Mediated Diseases].

Herein, the author summarize the basic findings on the neuropathology of inflammatory and autoimmune central nervous system (CNS) diseases. Current knowledge on infectious, demyelinating, and autoimmune diseases have also been reported. Further, I emphasize the importance of considering the neuropathology of meningitis, encephalitis, and abscesses as infectious diseases; multiple sclerosis and neuromyelitis optica as demyelinating diseases; and vasculitis, paraneoplastic neurological syndrome, and collagen diseases as autoimmune diseases.