Comprehensive High-Depth Proteomic Analysis of Plasma Extracellular Vesicles Containing Preparations in Rett Syndrome.

Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 females. Various treatments have been explored; however, no effective treatments have been reported to date, except for trofinetide, a synthetic analog of glycine-proline-glutamic acid, which was approved by the FDA in 2023. Serological biomarkers that correlate with the disease status of RTT are needed to promote early diagnosis and to develop novel agents.

Brain morphological analysis in mice with hyperactivation of the hedgehog signaling pathway.

Hedgehog signaling is a highly conserved pathway that plays pivotal roles in morphogenesis, tumorigenesis, osteogenesis, and wound healing. Previous investigations in patients with Gorlin syndrome found low harm avoidance traits, and increased volumes in the cerebrum, cerebellum, and cerebral ventricles, suggesting the association between brain morphology and the constitutive hyperactivation of hedgehog signaling, while the changes of regional brain volumes in upregulated hedgehog signaling pathway remains unclear so far. Herein, we investigated comprehensive brain regional volumes using quantitative structural brain MRI, and identified increased volumes of amygdala, striatum, and pallidum on the global segmentation, and increased volumes of the lateral and medial parts of the central nucleus of the amygdala on the detail segmentation in heterozygous deletion mice.

Increase in children with developmental delay: Survey on 18-month-old children in Togane city, Japan.

Background: Individuals who visit hospitals with neurodevelopmental disorders have recently increased. To locate the cause for this increase, various factors, such as environmental and genetic ones, are being investigated. The objective of this study is to analyze the developmental delay in children and their background.

Nationwide survey of childhood Guillain-Barré syndrome, Fisher syndrome, and Bickerstaff brainstem encephalitis in Japan.

Objective: Guillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan.

Specific temperament in patients with nevoid basal cell carcinoma syndrome.

Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a neurocutaneous disease, characterized by tumorigenesis and developmental anomalies due to aberrant sonic hedgehog (Shh) signaling. Patients with NBCCS typically appear calm and carefree, suggesting that a specific personality in these patients may be associated with an enhanced hedgehog pathway. Our study aimed to determine the personality type in these patients.

MicroRNAs profiling in fibroblasts derived from patients with Gorlin syndrome.

Gorlin syndrome (GS) is a hereditary disorder with tumorigenicity, caused by constitutive hyperactivity of hedgehog signaling. Smoothened (SMO) antagonists have been effectively used in the clinical treatment of hedgehog signaling-related cancer. However, these treatments have led to problematic side effects, including severe adverse reactions and drug resistance from additional somatic mutations.

Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and renal arteries.

Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen.

Brain morphology in children with nevoid basal cell carcinoma syndrome.

Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma.

Hedgehog signaling is synergistically enhanced by nutritional deprivation and ligand stimulation in human fibroblasts of Gorlin syndrome.

Hedgehog signaling is a pivotal developmental pathway that comprises hedgehog, PTCH1, SMO, and GLI proteins. Mutations in PTCH1 are responsible for Gorlin syndrome, which is characterized by developmental defects and tumorigenicity. Although the hedgehog pathway has been investigated extensively in Drosophila and mice, its functional roles have not yet been determined in human cells.

Anterior Commissure Involvement in Humanherpes Virus 6 Encephalitis.

The anterior commissure is an evolutionarily conserved nerve bundle that connects the right and left hemispheres, playing pivotal neurological roles in visual, linguistic, and olfactory functions. The authors herein describe a 16-month-old boy with high fever, lethargy, and recurrent seizures. Polymerase chain reaction (PCR) examination detected human herpesvirus 6 (HHV-6) in both the cerebrospinal fluid and the pharyngeal swabs, leading to the diagnosis of HHV-6 encephalitis.

Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1, encoding a receptor for the secreted protein, sonic hedgehog. Recently, a Chinese family with NBCCS carrying a missense mutation in PTCH2, a close homolog of PTCH1, was reported.

14-3-3 proteins, particularly of the epsilon isoform, are detectable in cerebrospinal fluids of cerebellar diseases in children.

Background: Detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is a powerful tool for elucidating the mechanisms of neurological disorders. There have been useful studies on 14-3-3 CSF protein detection in Creutzfeldt-Jakob disease and other neurological disorders, but none on cerebellar diseases.

Objective: To elucidate whether 14-3-3 CSF proteins are a sensitive biomarker of cerebellar disruption in children.

Phrenic nerve palsy associated with birth trauma--case reports and a literature review.

Phrenic nerve palsy is a peripheral nerve disorder caused by excessive cervical extension due to birth trauma or cardiac surgery. We describe two new patients with phrenic nerve palsy associated with birth trauma. Both patients exhibited profound dyspnea and general hypotonia immediately after birth.

Reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage.

We described a 7-year-old girl with reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage. She initially presented with high fever and pancytopenia, leading to a diagnosis of most severe type aplastic anemia. We treated her with cyclosporine, methylprednisolone and anti-thymocyte globulin.

Multiple cavitations in posterior reversible leukoencephalopathy syndrome associated with hemolytic-uremic syndrome.

We describe a 4-year-old boy with posterior reversible leukoencephalopathy syndrome associated with hemolytic-uremic syndrome. He exhibited bloody stool by Escherichia coli O157: H7 infection with acute renal failure. He subsequently presented high blood pressure, followed by visual disturbance and loss of consciousness.

[PTCH1 gene analysis in 25 Japanese patients with Gorlin syndrome].

Gorlin syndrome is an autosomal dominant disorder characterized by congenital anomalies and tumorigenesis. The gene responsible for Gorlin syndrome is PTCH1, a human homologue of the Drosophila segment polarity gene, patched. We analysed the PTCH1 gene in 25 patients in 22 families with Gorlin syndrome.

[Clinical manifestations in 25 Japanese patients with Gorlin syndrome].

We investigated the clinical manifestations of 25 Japanese patients with Gorlin syndrome. We revealed the frequencies of major five symptoms in Japanese Gorlin syndrome patients, i.e.

U7 snRNA-mediated correction of aberrant splicing caused by activation of cryptic splice sites.

A considerable fraction of mutations associated with hereditary disorders and cancers affect splicing. Some of them cause exon skipping or the inclusion of an additional exon, whereas others lead to the inclusion of intronic sequences or deletion of exonic sequences through the activation of cryptic splice sites. We focused on the latter cases and have designed a series of vectors that express modified U7 small nuclear RNAs (snRNAs) containing a sequence antisense to the cryptic splice site.

High-density oligonucleotide array with sub-kilobase resolution reveals breakpoint information of submicroscopic deletions in nevoid basal cell carcinoma syndrome.

Small submicroscopic genomic deletions and duplications constitute up to 15% of all mutations underlying human monogenic diseases. In this study, we used newly designed high-resolution oligonucleotide microarrays with a median distance between the probes of 776 bp (average probe interval 2,271 bp) to detect gene deletions in nevoid basal cell carcinoma syndrome (NBCCS) patients. NBCCS, also called Gorlin syndrome, is characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the human patched-1 (PTCH1) gene.

Acute motor axonal neuropathy during intensive immunosuppressive therapy for macrophage activation syndrome.

We describe a 2-year-old girl with refractory macrophage activation syndrome (MAS), which is a serious complication of inflammatory disorders associated with rheumatic disease in children. Although she was treated with intensive immunosuppressive therapies such as immunoglobulin, plasma exchange, dexamethasone, methotrexate, cyclosporine, and etoposide, she subsequently developed motor deficit with the abolition of deep tendon reflexes. Since nerve conduction study revealed low-amplitude compound muscle action potentials and motor conduction slowing, she was diagnosed as having acute motor axonal neuropathy (AMAN) associated with refractory MAS.

14-3-3 protein detection in the cerebrospinal fluid of patients with influenza-associated encephalopathy.

Influenza-associated encephalopathy is characterized by high fever, convulsions, and loss of consciousness associated with influenza infection in children, but its pathophysiology remains to be clarified. We examined 14-3-3 proteins, which are acidic brain proteins, in cerebrospinal fluid by immunoblotting in four patients with influenza-associated encephalopathy, four patients with influenza without encephalopathy, and four patients with another encephalopathy. Interestingly, we detected 14-3-3 proteins in all four patients with influenza-associated encephalopathy (100%) but not in any of the other patients.

Brain- and heart-specific Patched-1 containing exon 12b is a dominant negative isoform and is expressed in medulloblastomas.

Mutations in the human tumor suppressor gene, Patched-1, are associated with nevoid basal cell carcinoma syndrome characterized by developmental abnormalities and tumorigenesis, such as basal cell carcinoma and medulloblastoma. During the investigation of complex alternative splicing in Patched-1, we identified an alternative exon, exon 12b, located between exon 12 and 13, both in humans and in mice. Since exon 12b has an in-frame stop codon, the mRNA isoform containing this exon (Patched12b) encodes a truncated patched-1 protein.

Detection of 14-3-3 protein in the cerebrospinal fluid in mitochondrial encephalopathy with lactic acidosis and stroke-like episodes.

We describe a 13-year-old boy with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) who experienced a stroke-like episode resulting in severe mental regression and quadriplegia. We tested 14-3-3 protein in the cerebrospinal fluid (CSF) of the patient four times around a stroke-like episode in a magnetic resonance imaging (MRI) study. Detection of the protein in the CSF was well correlated with the clinical course and range of damage of the brain lesion on MRI.