RESUMO
Historically, the Wa-like strains of human group A rotavirus (RVA) have been major causes of gastroenteritis. However, since the 2010s, the circulation of non-Wa-like strains has been increasingly reported, indicating a shift in the molecular epidemiology of RVA. Although understanding RVA evolution requires the analysis of both current and historical strains, comprehensive pre-1980's sequencing data are scarce globally. We determined the whole-genome sequences of representative strains from six RVA gastroenteritis outbreaks observed at an infant home in Sapporo, Japan, between 1981 and 1989. These outbreaks were mainly caused by G1 or G3 Wa-like strains, resembling strains from the United States in the 1970s-1980s and from Malawi in the 1990s. Phylogenetic analysis of these infant home strains, together with Wa-like strains collected worldwide from the 1970s to 2020, revealed a notable trend: pre-2010 strains diverged into multiple lineages in many genomic segments, whereas post-2010 strains tended to converge into a single lineage. However, Bayesian skyline plot indicated near-constant effective population sizes from the 1970s to 2020, and selection pressure analysis identified positive selection only at amino acid 75 of NSP2. These results suggest that evidence supporting the influence of rotavirus vaccines, introduced globally since 2006, on Wa-like RVA molecular evolution is lacking at present, and phylogenetic analysis may simply reflect natural fluctuations in RVA molecular evolution. Evaluating the long-term impact of RV vaccines on the molecular evolution of RVA requires sustained surveillance.
Assuntos
Evolução Molecular , Gastroenterite , Genoma Viral , Filogenia , Infecções por Rotavirus , Rotavirus , Rotavirus/genética , Rotavirus/classificação , Rotavirus/isolamento & purificação , Humanos , Infecções por Rotavirus/virologia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/história , Japão/epidemiologia , Gastroenterite/virologia , Gastroenterite/epidemiologia , Gastroenterite/história , Sequenciamento Completo do Genoma , Surtos de Doenças , Lactente , Genótipo , Epidemiologia Molecular , História do Século XXRESUMO
Human adenovirus (HAdV) infections present diverse clinical manifestations upon infecting individuals, with respiratory infections predominating in children. We surveyed pediatric hospitalizations due to respiratory HAdV infections across 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to March 2024, recording 473 admissions. While hospitalizations remained below five cases per week from July 2019 to September 2023, a notable surge occurred in late October 2023, with weekly admissions peaking at 15-20 cases from November to December. There were dramatic shifts in the age distribution of hospitalized patients: during 2019-2021, 1-year-old infants and children aged 3-6 years represented 51.4%-54.8% and 4.1%-13.3%, respectively; however, in 2023-2024, while 1-year-old infants represented 19.0%-20.1%, the proportion of children aged 3-6 years increased to 46.2%-50.0%. Understanding the emergence of significant outbreaks of respiratory HAdV infections and the substantial changes in the age distribution of hospitalized cases necessitates further investigation into the circulating types of HAdV in Hokkaido Prefecture and changes in children's neutralizing antibody titers against HAdV.
Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Surtos de Doenças , Hospitalização , Infecções Respiratórias , Humanos , Japão/epidemiologia , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Pré-Escolar , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Criança , Adenovírus Humanos/isolamento & purificação , Adenovírus Humanos/classificação , Masculino , Feminino , Hospitalização/estatística & dados numéricos , LactenteRESUMO
Following the coronavirus disease 2019 (COVID-19) outbreak in February 2020, incidences of various infectious diseases decreased notably in Hokkaido Prefecture, Japan. However, Japan began gradually easing COVID-19 infection control measures in 2022. Here, we conducted a survey of children hospitalized with human metapneumovirus (hMPV), influenza A and B, and respiratory syncytial virus infections in 18 hospitals across Hokkaido Prefecture, Japan, spanning from July 2019 to June 2023. From March 2020 to June 2022 (28 months), only 13 patients were hospitalized with hMPV, and two patients had influenza A. However, in October to November 2022, there was a re-emergence of hMPV infections, with a maximum of 27 hospitalizations per week. From July 2022 to June 2023 (12 months), the number of hMPV-related hospitalizations dramatically increased to 317 patients, with the majority aged 3-6 years (38.2%, [121/317]). Influenza A also showed an increase from December 2022, with a peak of 13 hospitalizations per week in March 2023, considerably fewer than the pre-COVID-19 outbreak in December 2019, when rates reached 45 hospitalizations per week. These findings suggest the possibility of observing more resurgences in infectious diseases in Japan after 2023 if infection control measures continue to be relaxed. Caution is needed in managing potential outbreaks.
Assuntos
COVID-19 , Doenças Transmissíveis , Influenza Humana , Metapneumovirus , Infecções por Paramyxoviridae , Infecções por Vírus Respiratório Sincicial , Infecções Respiratórias , Criança , Humanos , Lactente , Influenza Humana/epidemiologia , Estações do Ano , Japão/epidemiologia , COVID-19/epidemiologia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologiaRESUMO
BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal medicineãhave improved the survival rates of preterm infants, neurodevelopmental disorders remain a significant complication. We tested whether the intravenous infusion of mesenchymal stem cells (MSCs) had therapeutic efficacy against perinatal brain injury in rats. METHODS: Pregnant rats at embryonic day (E) 18 received lipopolysaccharide and the pups were born at E21. On postnatal day (PND) 7, the left common carotid artery of each pup was ligated, and they were exposed to 8% oxygen for 2 h. They were randomized on PND10, and MSCs or vehicle were intravenously infused. We performed behavioral assessments, measured brain volume using MRI, and performed histological analyses on PND49. RESULTS: Infused MSCs showed functional improvements in our model. In vivo MRI revealed that MSC infusion increased non-ischemic brain volume compared to the vehicle group. Histological analyses showed that cortical thickness, the number of NeuN+ and GAD67+ cells, and synaptophysin density in the non-ischemic hemisphere in the MSC group were greater than the vehicle group, but less than the control group. CONCLUSIONS: Infused MSCs improve sensorimotor and cognitive functions in perinatal brain injury and enhance neuronal growth. IMPACT: Intravenous infusion of MSCs improved neurological function in rats with perinatal brain injury, including motor, sensorimotor, cognitive, spatial, and learning memory. Infused MSCs increased residual (non-ischemic) tissue volume, number of neuronal cells, GABAergic cells, and cortical synapses in the contralesional (right) hemisphere. Intravenous administration of MSC might be suitable for the treatment of perinatal brain injury.
Assuntos
Lesões Encefálicas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Ratos , Animais , Humanos , Recém-Nascido , Infusões Intravenosas , Ratos Sprague-Dawley , Recém-Nascido Prematuro , Lesões Encefálicas/terapia , Células-Tronco Mesenquimais/fisiologia , Modelos Animais de DoençasRESUMO
We isolated the rare G3P[9] rotavirus strain RVA/Human-wt/JPN/R11-035/2015/G3P[9] from a 2-year-old girl presenting with vomiting and diarrhea who had daily contact with cats in Japan, 2015. Full-genome analysis revealed that the R11-035 strain had an AU-1-like genetic constellation, except for the NSP3 (T) gene: G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis showed that strain R11-035 is closely related to human/feline-like human strains, and only the NSP3 (T1) gene was clustered together with Taiwanese porcine strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient and acquired its NSP3 gene through intergenotype reassortment with porcine strains before being transmitted to humans.
Assuntos
Gastroenterite , Infecções por Rotavirus , Rotavirus , Feminino , Humanos , Gatos , Animais , Criança , Suínos , Pré-Escolar , Infecções por Rotavirus/veterinária , Filogenia , Japão , Genoma Viral , Genótipo , Análise de SequênciaRESUMO
GNAO1 variants are associated with a wide range of neurodevelopmental disorders including epileptic encephalopathies and movement disorders. It has been reported that some GNAO1 variants are associated with movement disorders, and the 207-246 amino acid region was proposed as a mutational hotspot. Here, we report an intronic variant (NM_020988.3:c.724-8G>A) in GNAO1 in a Japanese girl who showed mild developmental delay and movement disorders including dystonia and myoclonus. Her movement disorders were improved by deep brain stimulation treatment as previously reported. This variant has been recurrently reported in four patients and was transmitted from her mother who possessed the variant as low-prevalent mosaicism. Using RNA extracted from lymphoblastoid cells derived from the patient, we demonstrated that the variant caused abnormal splicing of in-frame 6-bp intronic retention, leading to 2 amino acid insertion (p.Thr241_Asn242insProGln). Immunoblotting and immunostaining using WT and mutant GNAO1 vectors showed no significant differences in protein expression levels, but the cellular localization pattern of this mutant was partially shifted to the cytoplasm whereas WT was exclusively localized in the cellular membrane. Our report first clarified abnormal splicing and resulting mutant protein caused by the c.724-8G>A variant.
Assuntos
Estimulação Encefálica Profunda , Transtornos dos Movimentos , Aminoácidos , Feminino , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Humanos , Transtornos dos Movimentos/genética , MutaçãoRESUMO
PURPOSE: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.
Assuntos
Exoma , Malformações do Sistema Nervoso , Criança , Humanos , Exoma/genética , Mutação , Malformações do Sistema Nervoso/genética , Atrofia/genética , Receptor 1 de Folato/genética , CinesinasRESUMO
BACKGROUND: Hypertrophic pachymeningitis (HP) is a rare disorder characterized by diffuse thickening of the dura mater with resultant neurologic deficits. HP develops secondary to various conditions or idiopathically usually in adults but rarely in children. CASE REPORT: We describe a 3-year-old female child with idiopathic HP. Her HP involved the entire central nervous system with progression into the brainstem. The lesion responded poorly to pulsed steroids or any immunosuppressants. The brainstem lesion grew rapidly and formed various nodules that ultimately resulted in brain death. This is the first fatal case of HP in a child.
Assuntos
Acidentes por Quedas , Tronco Encefálico/diagnóstico por imagem , Progressão da Doença , Meningite/diagnóstico por imagem , Meningite/cirurgia , Pré-Escolar , Evolução Fatal , Feminino , Humanos , Hipertrofia/diagnóstico por imagem , Hipertrofia/etiologia , Hipertrofia/cirurgia , Meningite/etiologia , Fatores de TempoRESUMO
BACKGROUND: Constitutive activation of the PI3K-AKT-mTOR pathway (mTOR pathway) underlies megalencephaly in many patients. Yet, prevalence of the involvement of the PI3K-AKT-mTOR pathway in patients with megalencephaly remains to be elucidated, and molecular diagnosis is challenging. Here, we have successfully established a combination of genetic and biochemical methods for diagnosis of mTOR pathway-associated megalencephaly, and have attempted to delineate the clinical characteristics of the disorder. METHODS: Thirteen patients with an increased head circumference and neurological symptoms participated in the study. To evaluate the activation of the mTOR pathway, we performed western blot analysis to determine the expression levels of phosphorylated S6 ribosomal protein (phospho-S6 protein) in lymphoblastoid cell lines from 12 patients. Multiplex targeted sequencing analysis for 15 genes involved in the mTOR pathway was performed on 12 patients, and whole-exome sequencing was performed on one additional patient. Clinical features and MRI findings were also investigated. RESULTS: We identified pathogenic mutations in six (AKT3, 1 patient; PIK3R2, 2 patients; PTEN, 3 patients) of the 13 patients. Increased expression of phospho-S6 protein was demonstrated in all five mutation-positive patients in whom western blotting was performed, as well as in three mutation-negative patients. Developmental delay, dysmorphic facial features were observed in almost all patients. Syndactyly/polydactyly and capillary malformations were not observed, even in patients with AKT3 or PIK3R2 mutations. There were no common phenotypes or MRI findings among these patients. CONCLUSIONS: A combination of genetic and biochemical methods successfully identified mTOR pathway involvement in nine of 13 (approximately 70%) patients with megalencephaly, indicating a major contribution of the pathway to the pathogenesis of megalencephaly. Our combined approach could be useful to identify patients who are suitable for future clinical trials using an mTOR inhibitor.
Assuntos
Megalencefalia/diagnóstico , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Adolescente , Linhagem Celular , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Megalencefalia/genética , Megalencefalia/metabolismo , Mutação , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Análise de Sequência de DNA/métodos , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoAssuntos
Paralisia de Bell , Paralisia Facial , Síndrome de Linfonodos Mucocutâneos , Sincinesia , Nervo Facial , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Sincinesia/diagnóstico , Sincinesia/etiologiaRESUMO
INTRODUCTION: We report the case of a 2-year-old boy who showed a huge midline mass in the brain at prenatal assessment. CASE REPORT: After birth, magnetic resonance imaging (MRI) revealed a conglomerate mass with an infolded microgyrus at the midline, which was suspected as a midline brain-in-brain malformation. MRI also showed incomplete cleavage of his frontal cortex and thalamus, consistent with lobar holoprosencephaly. The patient underwent an incisional biopsy of the mass on the second day of life. The mass consisted of normal central nervous tissue with gray and white matter, representing a heterotopic brain. The malformation was considered to be a subcortical heterotopia. With maturity, focal signal changes and decreased cerebral perfusion became clear on brain imaging, suggesting secondary glial degeneration. Coincident with these MRI abnormalities, the child developed psychomotor retardation and severe epilepsy focused on the side of the intracranial mass.
Assuntos
Encéfalo/fisiopatologia , Coristoma/fisiopatologia , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Epilepsia/fisiopatologia , Holoprosencefalia/fisiopatologia , Encéfalo/patologia , Pré-Escolar , Coristoma/complicações , Coristoma/patologia , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/complicações , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/patologia , Eletroencefalografia , Epilepsia/etiologia , Feminino , Holoprosencefalia/complicações , Holoprosencefalia/patologia , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Gravidez , Transtornos Psicomotores/etiologia , Ultrassonografia Pré-NatalRESUMO
Objective: We examined the short-term efficacy and safety of rufinamide (RFN) in patients with Lennox-Gastaut syndrome (LGS). Methods: We performed a retrospective review of clinical records of patients with LGS who started RFN treatment between July 2013 and June 2014 at the Hokkaido Medical Center for Child Health and Rehabilitation and Midorigaoka Ryo-iku-en. Efficacy and safety were evaluated when the patients had completed three months of treatment. Patients were classified into four categories according to percent seizure reduction : remission (seizure-free), response (seizure reduction≥50%), no change (seizure reduction<50% or increase) and aggravation (seizure increase≥50%). Responder rate (RR) was the percentage of patients with≥50% decrease in seizure frequency. Results: Thirteen LGS patients (8 males, 5 females) were studied. The efficacy for tonic seizures (13 patients) was remission 1 patient, response 3 patients, no change 8 patients and aggravation 1 patient, with RR of 30.8%. Two patients discontinued LGS due to seizure aggravation. Four patients experienced transient remission. For generalized tonic clonic seizures (2 patients), 1 patient achieved remission and 1 patient showed no change. Two patients of atonic seizures showed no change. Of 2 patients of atypical absence, 1 patient showed response and 1 patient no change. Eight patients had adverse effects such as somnolence (6 patients), sleep disturbance (1 patient), and appetite loss (4 patients) including weight loss in 2 patients. There were no severe adverse effects and no discontinuation due to adverse effects. Conclusions: Short-term effectiveness for tonic seizures was observed when patients with LGS were treated with RFN, with transient remission in some patients. We consider that RFN is worth trying in patients with LGS due to its efficacy for tonic seizures and absence of severe adverse effects.
Assuntos
Anticonvulsivantes/uso terapêutico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Triazóis/uso terapêutico , Criança , Feminino , Humanos , Masculino , LinhagemRESUMO
Defects in the mitochondrial translation apparatus can impair energy production in affected tissues and organs. Most components of this apparatus are encoded by nuclear genes, including GFM2, which encodes a mitochondrial ribosome recycling factor. A few patients with mutations in some of these genes have been reported to date. Here, we present two female siblings with arthrogryposis multiplex congenita, optic atrophy and severe mental retardation. The younger sister had a progressive cerebellar atrophy and bilateral neuropathological findings in the brainstem. Although her cerebrospinal fluid (CSF) levels of lactate and pyruvate were not increased, brain magnetic resonance spectroscopy showed a lactate peak. Additionally, her CSF lactate/pyruvate and serum beta-hydroxybutyrate/acetoacetate ratios were high, and levels of oxidative phosphorylation in skin fibroblasts were reduced. We therefore diagnosed Leigh syndrome. Genomic investigation confirmed the presence of compound heterozygous GFM2 mutations (c.206+4A>G and c.2029-1G>A) in both siblings, causing aberrant splicing with premature stop codons (p.Gly50Glufs*4 and p.Ala677Leufs*2, respectively). These findings suggest that GFM2 mutations could be causative of a phenotype of Leigh syndrome with arthrogryposis multiplex congenita.
Assuntos
Artrogripose/genética , Doença de Leigh/genética , Proteínas Mitocondriais/genética , Fator G para Elongação de Peptídeos/genética , Artrogripose/complicações , Sequência de Bases , Criança , Evolução Fatal , Feminino , Heterozigoto , Humanos , Lactente , Doença de Leigh/complicações , Linhagem , IrmãosRESUMO
OBJECTIVE: It is sometime difficult to achieve effective blood levels of lamotrigine (LTG) by the methods of administration presented in the product labeling (PL). We highlighted the importance of measuring LTG blood levels, and proposed a method of adjusting the optimum dosage of LTG based on the pharmacokinetic interaction. METHOD: Four types of maintenance dose of LTG were determined whether LTG was administrated in combination with valproate sodium and/or enzyme-inducing antiepileptic drugs or with agents except for them. This method is compared with the method presented in the PL. We exhibited the clinical course of three patients who took LTG according to our method since the blood levels were not elevated enough by the method shown in the PL. RESULTS: The maintenance dosage described in the PL was lower than that in our methods. The blood levels in these three patients were increased enough to be effective after the therapy by our method. CONCLUSIONS: Measuring the LTG blood level is important to create an optimum dosing schedule. Since the maintenance doses of LTG presented in PL may be inappropriate, they should be adequately adjusted by reference to the LTG blood level.
Assuntos
Anticonvulsivantes/sangue , Epilepsia/tratamento farmacológico , Triazinas/sangue , Adolescente , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Lamotrigina , Masculino , Triazinas/administração & dosagem , Triazinas/uso terapêutico , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Biallelic mutations in the COA7 gene have been associated with spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3), and a notable clinical diversity has been observed. We aim to identify the genetic and phenotypic spectrum of COA7-related disorders. METHODS: We conducted comprehensive genetic analyses on the COA7 gene within a large group of Japanese patients clinically diagnosed with inherited peripheral neuropathy or cerebellar ataxia. RESULTS: In addition to our original report, which involved four patients until 2018, we identified biallelic variants of the COA7 gene in another three unrelated patients, and the variants were c.17A > G (p.D6G), c.115C > T (p.R39W), and c.449G > A (p.C150Y; novel). Patient 1 presented with an infantile-onset generalized dystonia without cerebellar ataxia. Despite experiencing an initial transient positive response to levodopa and deep brain stimulation, he became bedridden by the age of 19. Patient 2 presented with cerebellar ataxia, neuropathy, as well as parkinsonism, and showed a slight improvement upon levodopa administration. Dopamine transporter SPECT showed decreased uptake in the bilateral putamen in both patients. Patient 3 exhibited severe muscle weakness, respiratory failure, and feeding difficulties. A haplotype analysis of the mutation hotspot in Japan, c.17A > G (p.D6G), uncovered a common haplotype block. CONCLUSION: COA7-related disorders typically encompass a spectrum of conditions characterized by a variety of major (cerebellar ataxia and axonal polyneuropathy) and minor (leukoencephalopathy, dystonia, and parkinsonism) symptoms, but may also display a dystonia-predominant phenotype. We propose that COA7 should be considered as a new causative gene for infancy-onset generalized dystonia, and COA7 gene screening is recommended for patients with unexplained dysfunctions of the central and peripheral nervous systems.
Assuntos
Ataxia Cerebelar , Distonia , Distúrbios Distônicos , Transtornos Parkinsonianos , Humanos , Masculino , Ataxia Cerebelar/genética , Distúrbios Distônicos/complicações , Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/genética , Levodopa , Mutação/genética , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/genética , Fenótipo , Adulto JovemRESUMO
Variant annotations are crucial for efficient identification of pathogenic variants. In this study, we retrospectively analyzed the utility of four annotation tools (allele frequency, ClinVar, SpliceAI, and Phenomatcher) in identifying 271 pathogenic single nucleotide and small insertion/deletion variants (SNVs/small indels). Although variant filtering based on allele frequency is essential for narrowing down on candidate variants, we found that 13 de novo pathogenic variants in autosomal dominant or X-linked dominant genes are registered in gnomADv4.0 or 54KJPN, with an allele frequency of less than 0.001%, suggesting that very rare variants in large cohort data can be pathogenic de novo variants. Notably, 38.4% candidate SNVs/small indels are registered in the ClinVar database as pathogenic or likely pathogenic, which highlights the significance of this database. SpliceAI can detect candidate variants affecting RNA splicing, leading to the identification of four variants located 11 to 50 bp away from the exon-intron boundary. Prioritization of candidate genes by proband phenotype using the PhenoMatcher module revealed that approximately 95% of the candidate genes had a maximum PhenoMatch score ≥ 0.6, suggesting the utility of phenotype-based variant prioritization. Our results suggest that a combination of multiple annotation tools and appropriate evaluation can improve the diagnosis of rare diseases.
Assuntos
Sequenciamento do Exoma , Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/diagnóstico , Sequenciamento do Exoma/métodos , Criança , Frequência do Gene , Doenças Raras/genética , Doenças Raras/diagnóstico , Estudos Retrospectivos , Polimorfismo de Nucleotídeo Único , Mutação INDEL , Bases de Dados Genéticas , Exoma/genética , Anotação de Sequência Molecular , Predisposição Genética para Doença , Masculino , Fenótipo , FemininoRESUMO
BACKGROUND: Many reports have reported a reduction in respiratory infectious diseases and infectious gastroenteritis immediately after the coronavirus disease 2019 (COVID-19) pandemic, but data continuing into 2022 are very limited. We sought to understand the current situation of various infectious diseases among children in Japan as of July 2022 to improve public health in the post-COVID-19 era. METHODS: We collected data on children hospitalized with infectious diseases in 18 hospitals in Japan from July 2019 to June 2022. RESULTS: In total, 3417 patients were hospitalized during the study period. Respiratory syncytial virus decreased drastically after COVID-19 spread in early 2020, and few patients were hospitalized for it from April 2020 to March 2021. However, an unexpected out-of-season re-emergence of respiratory syncytial virus was observed in August 2021 (50 patients per week), particularly prominent among older children 3-6 years old. A large epidemic of delayed norovirus gastroenteritis was observed in April 2021, suggesting that the nonpharmaceutical interventions for COVID-19 are less effective against norovirus. However, influenza, human metapneumovirus, Mycoplasma pneumoniae , and rotavirus gastroenteritis were rarely seen for more than 2 years. CONCLUSIONS: The incidence patterns of various infectious diseases in Japan have changed markedly since the beginning of the COVID-19 pandemic to the present. The epidemic pattern in the post-COVID-19 era is unpredictable and will require continued careful surveillance.
Assuntos
COVID-19 , Doenças Transmissíveis , Gastroenterite , Infecções Respiratórias , Criança , Humanos , Adolescente , Pré-Escolar , COVID-19/epidemiologia , Criança Hospitalizada , Pandemias , Japão/epidemiologia , Gastroenterite/epidemiologia , Doenças Transmissíveis/epidemiologia , Vírus Sinciciais Respiratórios , Infecções Respiratórias/epidemiologiaRESUMO
This article reports the case of a female with late infantile neuronal ceroid lipofuscinosis who developed right and left anterior bundle branch blocks and episodic bradycardia at 23 years of age. Several episodes of supraventricular tachycardia manifested at 23 and 27 years of age. In addition, a transient second-degree atrioventricular conduction block also emerged at 27 years of age. Atrial fibrillation and aggravation of the atrioventricular conduction block resulted in progressive bradycardia and cardiac death at the age of 28 years. Cardiac involvement and accumulation of lipopigments in the myocardium and cardiac conduction system have been recognized in juvenile neuronal ceroid lipofuscinosis, but this is the first report to describe progressive conduction defects in a case of late infantile neuronal ceroid lipofuscinosis.
Assuntos
Arritmias Cardíacas/etiologia , Sistema de Condução Cardíaco/fisiopatologia , Lipídeos , Lipofuscinoses Ceroides Neuronais/complicações , Lipofuscinoses Ceroides Neuronais/fisiopatologia , Adulto , Fibrilação Atrial/etiologia , Bloqueio Atrioventricular/etiologia , Bradicardia/etiologia , Criança , Progressão da Doença , Ecocardiografia , Eletrocardiografia , Eletroencefalografia , Nutrição Enteral , Evolução Fatal , Feminino , Sistema de Condução Cardíaco/metabolismo , Humanos , Masculino , Miocárdio/metabolismo , Lipofuscinoses Ceroides Neuronais/metabolismo , Taquicardia Supraventricular/etiologia , Fibrilação Ventricular/etiologiaRESUMO
We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at 2-3 years after its onset. The chronic headaches were refractory to various anti-migraine and analgesic agents, persisted for 3-6 months in each patient, and rendered them unable to attend school. These headaches commonly manifested with symptoms of orthostatic dysregulation and paroxysmal back/limb pain. In addition, T2-weighted magnetic resonance images showed dots of highly intense signals in the bilateral cerebral white matter. Neurotropin, a non-protein extract isolated from the dermis of rabbits and inoculated with the vaccinia virus, induced prompt significant effects on the headache and back/limbs pain in both the girls. The symptom of orthostatic dysregulation was also gradually ameliorated after the resolution of the headache. Neurotropin has an analgesic action that is not common to other drugs since it enhances the descending pain inhibitory systems, and its effect has been reported in cases of post-herpetic and other neuralgia as well as in cases of primary headaches in adulthood. This agent may also be promising for the treatment of intractable primary headaches during childhood.