RESUMO
Canine Degenerative Myelopathy is a late onset recessive autosomal disease characterized by a progressive ascending degeneration of the spinal cord. Two causal mutations are associated with this disease: a transition (c.118G>A) in exon 2 of the SOD1 that was described in several breeds and a transversion (c.52A>T) in exon 1 of the same gene described in Bernese Mountain dogs. The aim of this study was to understand the impact of the SOD1:c.118G > A mutation by genotyping a population of German Shepherd dogs in Brazil. A PCR-RFLP approach was used to genotype 97 healthy individuals belonging from the Northeast (Bahia and Pernambuco states) and South (Santa Catarina state) regions of Brazil. A total of 95 individuals were successfully genotyped resulting in an observed genotype frequency (with 95% confidence interval) of: 0.758 (0.672-0.844), 0.242 (0.156-0.328) and 0.000 (0.000-0.000) for "GG", "AG" and "AA" genotypes, respectively. To our knowledge, this is the first attempt to describe the presence of the "A" allele associated with CDM (SOD1:c.118G > A) in German Shepherd dogs in Brazil and, as such, these results contribute toward important epidemiological data in this country and to the knowledge of the distribution of the aforementioned mutation worldwide.
Assuntos
Doenças da Medula Espinal/genética , Superóxido Dismutase-1/genética , Alelos , Animais , Brasil/epidemiologia , Cruzamento , Mapeamento Cromossômico , Doenças do Cão/genética , Cães , Genótipo , Mutação , Medula Espinal/patologia , Doenças da Medula Espinal/veterinária , Superóxido Dismutase/genética , Superóxido Dismutase-1/metabolismoRESUMO
Most human T-lymphotropic virus type 1 (HTLV-1)-infected patients remain asymptomatic throughout life. The factors associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development have not been fully elucidated; immunological and genetic factors may be involved. The association of 14 bp INS/DEL HLA-G polymorphism with HTLV-1 infection susceptibility has been reported previously. Here, other polymorphic sites at the HLA-G 3'-UTR (14-bp D/I, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G and +3196C/G) were evaluated in 37 HTLV-1-infected individuals exhibiting HAM/TSP, 45 HTLV-1 asymptomatic carriers (HAC) and 153 uninfected individuals, followed up at University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. It was observed that: (i) 14bpDI genotype is a risk factor for HTLV-1 infection, while the 14bpDD and +3142CC genotypes were associated with protection against infection; (ii) the +3142C allele and the +3003CT and +3142CC genotypes were associated with susceptibility, while 14bpII and +3003TT genotypes were associated with protection against HAM/TSP development; and (iii) the 14bpII, +3010CC, +3142GG and +3187AA genotypes were associated with lower HTLV-1 proviral load compared to respective counterpart genotypes. Findings that HLA-G has a well-recognized immunomodulatory role and that the genetic variability at HLA-G 3'-UTR may post-transcriptionally modify HLA-G production indicate a differential genetic susceptibility to: (i) the development of HTLV-1 infection, (ii) the magnitude of HTLV-1 proviral load and (iii) HAM/TSP development.
Assuntos
Regiões 3' não Traduzidas , Antígenos HLA-G/genética , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Paraparesia Espástica Tropical/genética , Polimorfismo Genético , Provírus/fisiologia , Doenças da Medula Espinal/genética , Adolescente , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Antígenos HLA-G/imunologia , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , Provírus/genética , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/virologia , Adulto JovemRESUMO
X-linked adrenoleukodystrophy heterozygote women can present adult onset myeloneuropathy and little is known about its natural history. We aimed to describe the progression rate of the neurological impairment in the prospective follow-up of our cohort and to look for prognostic factors. The neurological scales Japanese Orthopaedic Association (JOA) and Severity Score System for Progressive Myelopathy (SSPROM) were applied at baseline in 29 symptomatic carriers and in follow-up visits. Age at onset, disease duration, X inactivation pattern, determination of the allele expressed, plasma levels of the very long chain fatty acids and of the neuron-specific enolase, and somato-sensory evoked potentials, were taken at baseline. The slope of the linear regression of both JOA and SSPROM versus disease duration since the first symptom was estimated using mixed modeling. JOA and SSPROM decreased 0.42 and 1.87 points per year, respectively (p < 0.001). None of the parameters under study influenced these rates. We estimated that the number of carriers per arm needed in a future 12 month trial with 80% power and a 50% reduction in disease progression would be 225 women for JOA and 750 for SSPROM. The progression rates of the studied neurological scales were small, did not depend on any modifier factor known, and reflected the characteristically slow worsening of symptoms in X-ALD heterozygotes. Better biomarkers are still necessary for future studies.
Assuntos
Adrenoleucodistrofia/diagnóstico , Adrenoleucodistrofia/genética , Progressão da Doença , Heterozigoto , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/genética , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
O controle da carga proviral do HTLV-1 depende em parte da lise de células infectadas por células citotóxicas mediada pelos linfócitos T CD8⁺ e pelas células NK (Natural killer). A família de receptores KIR (killer-cell immunoglobulin-like receptor) interage com as moléculas de HLA de classe I, principalmente os alelos do HLA C do grupo 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 e C*16), ativando ou inibindo a função destas células.O objetivo do presente estudo foi avaliar se os genes KIR2DL2/KIR2DL3 e os alelos de HLA-C do grupo 1 estão associados ao controle da carga proviral do HTLV-1 e ao diagnóstico de HAM/TSP. O estudo foi realizado no Centro de HTLV da Escola Bahiana de Medicina e Saúde Púbica, em Salvador-Bahia. A presença dos genes KIR2DL2 e KIR2DL3 foi determinada por PCR em tempo real (Syber Green). Foram incluídos 248 indivíduos infectados pelo HTLV-1 (161 assintomáticos e 87 com HAM/TSP) cujos alelos de HLA de classe I haviam sido previamente determinados. A carga proviral (quantificada por PCR em tempo real) e as frequências de indivíduos assintomáticos e com diagnóstico de HAM/TSP (Possível, Provável e Definido) foram comparadas de acordo com a presença ou ausência dos genes KIR avaliados. As frequências dos genes KIR2DL2 e KIR2DL3 foi 84,3% e 96,8%...
The control of proviral load of HTLV-1 depends in part of the lysis of infected cells mediated by cytotoxic CD8⁺T lymphocytes and NK (Natural killer) cells. The family of KIR (killer-cell immunoglobulin-like receptor) interacts with HLA class I molecules, especially those HLA-C alleles in-group 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 and C*16) by activating or inhibiting the function of these cells. The aim of this study was to evaluate if the KIR2DL2, KIR2DL3 genes and group 1 HLA-C alleles are associated with the control of proviral load of HTLV-1 and the diagnosis of HAM/TSP. The study was performed at Bahiana School HTLV Center of Medicine and Health Public, in Salvador, Bahia. The presence of KIR2DL2 and KIR2DL3 genes was determined by real-time PCR (Syber Green). The study included 248 subjects infected with HTLV-1(161 and 87 asymptomatic with HAM/TSP) whose HLA class I alleles were previously determined. The proviral load (quantified by real-time PCR) and the frequency asymptomatic individuals diagnosed with HAM/TSP (possibly, probably and definitive) were compared according to the presence or absence of KIR genes evaluated. The frequencies of KIR2DL2 and KIR2DL3 genes were 84.3% and 96.8%...
Assuntos
Humanos , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/genética , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/patologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidadeRESUMO
We investigated a possible association of collagen IX tryptophan (Trp) alleles (Trp2 and Trp3) and smoking with cervical spondylotic myelopathy (CSM) in 172 Chinese patients and 176 age- and gender-matched controls. The smoking status was evaluated by smoking index (SI). The CSM cases had a significantly higher prevalence of Trp2 alleles (Trp2+) than controls (19.8 vs 6.2%, P = 0.002), but the prevalence of Trp3 alleles (Trp3+) was similar between the two groups (23.3 vs 21.6%, P = 0.713). Logistic regression analyses showed that the subjects with Trp2+ had a higher risk for CSM. We thus analyzed whether smoking status influenced the association between Trp2 alleles and CSM risk. Among Trp2+ subjects with an SI less than 100, the smoking status did not influence the effect of risk for SCM [odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 0.85-2.18, P > 0.05]. When SI increased from 101 to 300, the OR for CSM reached 3.34 (95%CI = 2.11-5.67, P = 0.011); when SI was more than 300, the OR for CSM reached 5.56 (95%CI = 3.62-7.36, P < 0.001). Among Trp2- subjects with SI more than 300, the OR for CSM increased 2.14 (95%CI = 1.15-4.07, P = 0.024). We found a significant association between the Trp2 alleles and CSM risk and smoking amplifies this risk, suggesting that smoking abstinence is important for reducing CSM occurrence in subjects with high genetic risk.
Assuntos
Colágeno Tipo IX/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fumar , Doenças da Medula Espinal/genética , Espondilose/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
The human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive disease causing paraparesis of the lower limbs. Only a minority of persons infected with HTLV-1 develop HAM/TSP. Universal susceptibility factors for HAM/TSP are not known. The viral genotype is similar in asymptomatic carriers and HAM/TSP patients. High proviral load has been associated consistently with HAM/TSP, but this factor does not explain fully the presence of disease in HTLV-1-infected subjects. Most likely, host genetic factors will play an important role in HAM/TSP development. A two-stage case-control study was carried out to evaluate the association between HAM/TSP and candidate single nucleotide polymorphisms (SNPs) from 45 genes in addition to six human leukocyte antigen (HLA) alleles. Ancestry-informative markers were used to correct for population stratification. Several SNPs belonging to NFKB1A and NKG2D showed a trend of association in both stages. The fact that the direction of the association observed in the first stage was the same in the second stage suggests that NFKB1A and NKG2D may be implicated in the development of HAM/TSP. Further replication studies in independent HTLV-1 patient groups should validate further these associations.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Subunidade p50 de NF-kappa B/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Paraparesia Espástica Tropical/genética , Doenças da Medula Espinal/genética , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Mapeamento Cromossômico , Feminino , Predisposição Genética para Doença , Genótipo , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , Peru , Polimorfismo de Nucleotídeo Único , Provírus/imunologia , Provírus/patogenicidade , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/virologia , Carga ViralRESUMO
We present a case of a patient who received nitrous oxide on two occasions within a period of 8 weeks and who subsequently developed a diffuse myelopathy, characterized by upper extremity paresis, lower extremity paraplegia and neurogenic bladder. Laboratory testing revealed hyperhomocysteinaemia and low levels of vitamin B(12). Because of this uncommon clinical presentation, we analysed the patient's DNA, and found a polymorphism in the MTHFR gene that is associated with the thermolabile isoform of the 5,10-methylenetetrahydrofolate reductase enzyme, which explained the myelopathy experienced by the patient after being exposed to nitrous oxide. Soon after initiating supplementary therapy with folic acid and vitamin B(12), the neurological symptoms subsided.
Assuntos
Anestésicos Inalatórios/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Óxido Nitroso/efeitos adversos , Polimorfismo Genético , Doenças da Medula Espinal/induzido quimicamente , Ácido Fólico/uso terapêutico , Predisposição Genética para Doença , Humanos , Hiper-Homocisteinemia/complicações , Masculino , Pessoa de Meia-Idade , Paralisia/induzido quimicamente , Complicações Pós-Operatórias , Doenças da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/genética , Vitamina B 12/uso terapêuticoRESUMO
La enfermedad de Werdning-Hoffmann o Atrofia Muscular Espinal, se caracteriza por cursar con hipotonía, debilidad muscular y disminución o ausencia de los refejos osteo-tendinosos. Se presenta a una lactante mayor, femenina de 20 meses, referida como "Síndrome del Niño Hipotónico", con hipotonía y debilidad muscular, para su evaluación genética. Fue estudiada clínica y paraclínicamente, siendo portadora de una Enfermedad de Werdnig-Hoffmann. Fallece a los 20 meses a consecuencia de un cuadro respiratorio bronconeumónico. La madre refiere cuatro hijos anteriores (dos varones y dos hembras) con igual cuadro neurológico, falleciendo alrededor de los 14 meses de edad, por cuadros respiratorios. Aun cuando, clásicamente, la Atrofia Muscular Espinal es transmitida mediante patrón mendeliano autosómico recesivo, casos de dominancia han sido reportados en la literatura. Es de hacer notar la frecuencia de pacientes afectos (cinco de un total de ocho hijos) en el grupo familiar en estudio
Assuntos
Lactente , Humanos , Feminino , Doenças da Medula Espinal/genética , Hipóxia Encefálica/diagnóstico , Atrofia Muscular/genéticaRESUMO
Four members of a family with spinocerebellar degeneration and slow saccadic eye movements are described. Detailed electrophysiological studies revealed abnormalities of neurological pathways not apparent clinically. The patients had slow saccades as measured electrophysiologically, as well as absence of rapid eye movements (REM) despite REM stages of sleep. These studies suggest that although saccadic eye movement and REM are mediated through the pontine paramedian reticular formation, other characteristics of REM sleep are not necessarily mediated through the same neurons.
Assuntos
Doenças Cerebelares/genética , Movimentos Oculares , Movimentos Sacádicos , Sono REM , Doenças da Medula Espinal/genética , Adulto , Doenças Cerebelares/fisiopatologia , Criança , Eletroencefalografia , Eletromiografia , Potenciais Evocados , Potenciais Somatossensoriais Evocados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Doenças da Medula Espinal/fisiopatologiaRESUMO
The cases of three brothers with proximal weakness and muscles atrophies beginning in childhood are reported. Muscles biopsies and electromyographic studies have shown neurogenic pattern of atrophy and a dystrophy-like picture. It is concluded that this histological and eletromyographic picture can occur in pure partial denervation of long standing. The histopathologic study of the spinal cord of one patient revealed degenerative changes and loss of anterior horn ganglion cells. This is the fourth case of Wohlfar-Kugelberg-Welander disease with postmortem examination.