RESUMO
Four patients with encephalitis/encephalopathy and parenchymal lesions accompanying reversible splenial lesions were retrospectively evaluated. In 3 patients, reversible lesions with transiently reduced diffusion were seen in the splenium and symmetrically in the peripheral frontoparietal white matter, clinical signs and symptoms were mild, and recovery was complete. These and previous observations suggest a less severe course and outcome for patients with reversible lesions isolated to the splenium or to the splenium and peripheral frontoparietal white matter.
Assuntos
Encefalopatias/patologia , Corpo Caloso/patologia , Encefalite/patologia , Imageamento por Ressonância Magnética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Remissão Espontânea , Estudos RetrospectivosRESUMO
Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p=0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p=0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p=0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p=0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.
Assuntos
Encefalopatias/genética , Citocinas/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Canais de Sódio/genética , Encefalopatias/complicações , Criança , Pré-Escolar , Epilepsias Parciais/complicações , Feminino , Genótipo , Humanos , Lactente , Japão , Masculino , Estudos Retrospectivos , Convulsões Febris/complicaçõesRESUMO
Chromosomal aberrations involving 8q11.2 have been reported in lipoblastoma. We report here a case of lipoblastoma with new chromosomal aberration. 46,XX,ins(8;6)(q11.2;q13q27). Cytogenetic analysis would facilitate the clinical differentiation between myxoid liposarcoma and the pathologically similar lipoblastoma and the identification of genetic loci related to cellular growth.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 6 , Cromossomos Humanos Par 8 , Lipoma/genética , Feminino , Humanos , Lactente , Lipoma/patologiaRESUMO
The case of a 3-year-old male with type 3 Gaucher's disease, whose genotype for the beta-glucosidase gene was D409H/unknown mutation, is presented. After the onset of visceral and neurologic signs during infancy, a radiologic investigation at 3 years of age revealed communicating hydrocephalus, an unusual complication of Gaucher's disease. A ventriculoperitoneal shunt operation led to clinical and radiologic improvement. The possibility of this complication should be considered in the treatment of patients with Gaucher's disease.
Assuntos
Doença de Gaucher/complicações , Doença de Gaucher/genética , Hidrocefalia/etiologia , Mutação , beta-Glucosidase/genética , Pré-Escolar , Genótipo , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/genética , Hidrocefalia/cirurgia , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Derivação VentriculoperitonealRESUMO
We report an 11-year-old girl with Chiari type I malformation and syringomyelia, who experienced isolated sleep apnea without other neurologic problems. Monitoring with oximetry and movement of thoracic and abdominal walls indicated mixed-type sleep apnea. Chiari type I malformation should be differentiated from other disorders causing sleep apnea.
Assuntos
Malformação de Arnold-Chiari/complicações , Síndromes da Apneia do Sono/etiologia , Siringomielia/complicações , Malformação de Arnold-Chiari/classificação , Criança , Feminino , Humanos , Síndromes da Apneia do Sono/cirurgiaRESUMO
In vitro and in vivo antibacterial activities and pharmacokinetics of M14659 were investigated. In vitro activity of M14659 was superior to that of ceftazidime against Staphylococcus aureus. Against Gram-negative bacteria except Pseudomonas aeruginosa, its activity was almost equal to that of ceftazidime. M14659 was more active against P. aeruginosa including multi-drug resistant strains than cefsulodin, cefoperazone or ceftazidime. Affinities of M14659 for penicillin-binding proteins (PBPs) of Escherichia coli and P. aeruginosa were 2 to 14 times higher for PBP-1A and PBP-1B than found for ceftazidime, and almost the same for PBP-3. In vivo activity of M14659 against S. aureus was superior to that of cefamandole, cefotaxime or ceftazidime. Against Gram-negative bacteria including P. aeruginosa, M14659 was 2 to 220 times more active than cefotaxime or ceftazidime. Plasma half-life of M14659 in mice was about 3 times longer than that of ceftazidime. M14659 administered intravenously to mice was mainly excreted in urine without metabolism, and its recovery rate was almost equal to that of ceftazidime.
Assuntos
Proteínas de Bactérias , Cefalosporinas/farmacologia , Hexosiltransferases , Peptidil Transferases , Animais , Infecções Bacterianas/tratamento farmacológico , Proteínas de Transporte/antagonistas & inibidores , Cefalosporinas/farmacocinética , Hidrólise , Injeções , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Muramilpentapeptídeo Carboxipeptidase/antagonistas & inibidores , Proteínas de Ligação às Penicilinas , Ligação Proteica , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
BACKGROUND: ARX is a paired-type homeobox gene located on the X chromosome that contains five exons with four polyalanine (PolyA) tracts, a homeodomain, and a conserved C-terminal aristaless domain. Studies in humans have demonstrated remarkable pleiotropy: malformation phenotypes are associated with protein truncation mutations and missense mutations in the homeobox; nonmalformation phenotypes, including X-linked infantile spasms (ISS), are associated with missense mutations outside of the homeobox and expansion of the PolyA tracts. OBJECTIVE: To investigate the role of ARX, we performed mutation analysis in 115 boys with cryptogenic ISS. This included two pairs of brothers. RESULTS: We found an expansion of the trinucleotide repeat that codes for the first PolyA tract from 10 to 17 GCG repeats (c.333_334ins[GCG]7) in six boys (5.2%) ages 2 to 14, from four families, including the two pairs of brothers. In addition to ISS, all six boys had severe mental retardation and generalized dystonia that appeared around the age of 6 months and worsened, eventually leading to stable severe quadriplegic dyskinesia within age 2 years. Three children experienced recurrent, life-threatening status dystonicus. In four children brain MRI showed multiple small foci of abnormal cavitation on T1 and increased signal intensity on T2 in the putamina, possibly reflecting progressive multifocal loss of tissue. CONCLUSION: The phenotype of infantile spasms with severe dyskinetic quadriparesis increases the number of human disorders that result from the pathologic expansion of single alanine repeats. ARX gene testing should be considered in boys with infantile spasms and dyskinetic cerebral palsy in the absence of a consistent perinatal history.
Assuntos
Distúrbios Distônicos/genética , Proteínas de Homeodomínio/genética , Deficiência Intelectual/genética , Mutação/genética , Espasmos Infantis/genética , Fatores de Transcrição/genética , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Alanina/genética , Atrofia/genética , Atrofia/patologia , Atrofia/fisiopatologia , Gânglios da Base/anormalidades , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Distúrbios Distônicos/metabolismo , Distúrbios Distônicos/fisiopatologia , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Recém-Nascido , Deficiência Intelectual/metabolismo , Deficiência Intelectual/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Linhagem , Fenótipo , Espasmos Infantis/metabolismo , Espasmos Infantis/fisiopatologiaRESUMO
We investigated the molecular basis of holoprosencephaly in a sporadic patient and identified a novel missense mutation in the signal sequence of the sonic hedgehog (Shh) gene. Magnetic resonance imaging of the head showed a lobar type of holoprosencephaly and partial agenesis of the anterior corpus callosum. He was treated for craniosynostosis at 7 months of age. All three exons of the Shh gene were amplified by polymerase chain reaction from genomic DNA of the patient and controls. Sequencing analysis of the polymerase chain reaction fragments, screened by single-strand conformation polymorphism analysis, revealed a heterozygous mutation of a T-to-C substitution at nucleotide position 50. This mutation predicted an amino acid replacement of leucine to proline at codon 17 located in the signal peptide of SHH protein. It probably disturbs the translocation of the protein into the endoplasmic reticulum and may lead to holoprosencephaly because of haploinsufficiency of Shh.