RESUMEN
Defects in the biogenesis of peroxisomes cause a clinically and genetically heterogeneous group of neurometabolic disorders, the Zellweger syndrome spectrum (ZSS). Diagnosis predominantly is based on characteristic clinical symptoms, a typical biochemical profile, as well as on identification of the molecular defect in any of the 12 known human PEX genes. The diagnostic workup can be hindered if the typical clinical symptoms are missing and predicting the clinical course of a given patient is almost unfeasible. As a safe and noninvasive method to analyze specific chemical compounds in localized brain regions, in vivo proton magnetic resonance spectroscopy (MRS) can provide an indication in this diagnostic process and may help predict the clinical course. However, to date, there are very few reports on this topic. In this study, we performed localized in vivo proton MRS without confounding contributions from T1- and T2-relaxation effects at 2 Tesla in a comparably large group of seven ZSS patients. Patients' absolute metabolite concentrations in cortical gray matter, white matter, and basal ganglia were assessed and compared with age-matched control values. Our results confirm and extend knowledge about in vivo MRS findings in ZSS patients. Besides affirmation of nonspecific reduction of N-acetylaspartate + N-acetylaspartylglutamate (tNAA) in combination with lipid accumulation as a diagnostic hint for this disease group, the amount of tNAA loss seems to reflect disease burden and may prove to be of prognostic value regarding the clinical course of an already diagnosed patient.
Asunto(s)
Síndrome de Zellweger/diagnóstico , Síndrome de Zellweger/patología , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Ganglios Basales/metabolismo , Ganglios Basales/patología , Niño , Dipéptidos/metabolismo , Femenino , Sustancia Gris/metabolismo , Sustancia Gris/patología , Humanos , Lactante , Espectroscopía de Resonancia Magnética/métodos , Masculino , Peroxisomas/metabolismo , Peroxisomas/patología , Pronóstico , Protones , Sustancia Blanca/metabolismo , Sustancia Blanca/patología , Adulto Joven , Síndrome de Zellweger/metabolismoRESUMEN
BACKGROUND: The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. OBJECTIVE: Characterization of four new XP-A patients. METHODS: Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting. RESULTS: One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. CONCLUSION: We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles.
Asunto(s)
Reparación del ADN/genética , ARN Mensajero/metabolismo , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Xerodermia Pigmentosa/genética , Adolescente , Adulto , Niño , Análisis Mutacional de ADN , Fibroblastos , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/genética , Masculino , Mutación , Fenotipo , Cultivo Primario de Células , ARN Mensajero/análisis , Análisis de Secuencia de ARN , Trastornos del Habla/complicaciones , Trastornos del Habla/genética , Xerodermia Pigmentosa/complicaciones , Proteína de la Xerodermia Pigmentosa del Grupo A/química , Adulto JovenRESUMEN
BACKGROUND: Pelizaeus-Merzbacher-like disease (PMLD) is a genetically heterogeneous disorder within the group of hypomyelinating leukoencephalopathies. Mutations of the gap junction protein alpha 12 (GJA12) gene are known to cause one autosomal recessive PMLD form. Few patients with GJA12 mutated PMLD have been reported, and to date, the frequency as well as the genotypic and phenotypic spectrum of GJA12 related PMLD is unclear. METHODS: We report mutation analysis of the GJA12 gene in a clinical and radiologic well-characterized multiethnic cohort of 193 patients with PMLD from 182 families. RESULTS AND CONCLUSIONS: Only 16 patients (8.3%) from 14 families (7.7%) carry GJA12 mutations including five families where we detected only one mutated allele. Among those, we identified 11 novel alterations. Thus, GJA12 mutations are a rather rare cause for Pelizaeus-Merzbacher-like disease. The clinical phenotype of patients with a GJA12 mutation was evaluated and is overall comparable to the clinical features seen in mild forms of proteolipid protein 1 (PLP1) related disorder but with better cognition and earlier signs of axonal degeneration.
Asunto(s)
Conexinas/genética , Uniones Comunicantes/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Enfermedad de Pelizaeus-Merzbacher/genética , Adolescente , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Encéfalo/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Proteína Proteolipídica de la Mielina/genética , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Mielínicas/patología , Oligodendroglía/metabolismo , Oligodendroglía/patología , Enfermedad de Pelizaeus-Merzbacher/metabolismo , Enfermedad de Pelizaeus-Merzbacher/fisiopatología , Fenotipo , Degeneración Walleriana/genética , Degeneración Walleriana/metabolismo , Degeneración Walleriana/fisiopatologíaRESUMEN
In this pediatric case of vanishing white matter disease with early onset, rapidly progressive course, and fatal outcome, the white matter vanishing process in patient was for the first time documented morphologically in detail: An initial magnetic resonance imaging documented a normal appearing brain maturation. Rapid progressive brain lesions initiated morphologically DE NOVO in the former well myelinated deep white matter were observed six months later after disease onset, including concentric ongoing signs of restricted proton diffusion cytotoxic edema on diffusion weighted imaging. Cyst-like defects at the lesion center of the deep white matter were detected more clearly on MRI ten months later. A pathomechanism like tumor necrosis factor induced oligodendrocyte apoptosis and primary demyelination was postulated. The case demonstrates that in the presence of clinically progressive symptoms, the development of VWM is possible even if first MRI findings are negative.
Asunto(s)
Encefalopatías/patología , Imagen por Resonancia Magnética/métodos , Atrofia/patología , Preescolar , Progresión de la Enfermedad , Femenino , HumanosRESUMEN
Cytochrome c oxidase deficiency (COX) is the most frequent cause of Leigh syndrome (LS), a mitochondrial subacute necrotizing encephalomyelopathy. Most of these LS (COX-) patients show mutations in SURF1 on chromosome 9 (9q34), which encodes a protein essential for the assembly of the COX complex. We describe a family whose first-born boy developed characteristic features of LS. Severe COX deficiency in muscle was caused by a novel homozygous nonsense mutation in SURF1. Segregation analysis of this mutation in the family was incompatible with autosomal recessive inheritance but consistent with a maternal disomy. Haplotype analysis of microsatellite markers confirmed isodisomy involving nearly the complete long arm of chromosome 9 (9q21-9tel). No additional physical abnormalities were present in the boy, suggesting that there are no imprinted genes on the long arm of chromosome 9 which are crucial for developmental processes. This case of segmental isodisomy illustrates that genotyping of parents is crucial for correct genetic counseling.
Asunto(s)
Deficiencia de Citocromo-c Oxidasa/genética , Enfermedad de Leigh/genética , Proteínas/genética , Disomía Uniparental/genética , Preescolar , Femenino , Homocigoto , Humanos , Lactante , Recién Nacido , Enfermedad de Leigh/diagnóstico , Masculino , Proteínas de la Membrana , Proteínas Mitocondriales , Linaje , Embarazo , Diagnóstico Prenatal , Disomía Uniparental/diagnósticoRESUMEN
OBJECTIVE: To analyse the PEX1 gene, the most common cause for peroxisome biogenesis disorders (PBD), in a consecutive series of patients with Zellweger spectrum. METHODS: Mutations were detected by different methods including SSCP analyses as a screening technique on the basis of genomic or cDNA, followed by direct sequencing of PCR fragments with an abnormal electrophoresis pattern. RESULTS: 33 patients were studied. Two common mutations, c.2528G-->A, G843D and c.2098_2098insT, I700YfsX42, accounted for over 80% of all abnormal PEX1 alleles, emphasising their diagnostic relevance. Most PEX1 mutations were distributed over the two AAA cassettes with the two functional protein domains, D1 and D2, and the highly conserved Walker motifs. Phenotypic severity of Zellweger spectrum in CG1 depended on the effect of the mutation on the PEX1 protein, peroxin 1. PEX1 mutations could be divided into two classes of genotype-phenotype correlation: class I mutations led to residual PEX1 protein levels and function and a milder phenotype; class II mutations almost abolished PEX1 protein levels and function, resulting in a severe phenotype. Compound heterozygote patients for a class I and class II mutation had an intermediate phenotype. CONCLUSIONS: Molecular confirmation of the clinical and biochemical diagnosis will allow the prediction of the clinical course of disease in individual PBD cases.
Asunto(s)
Proteínas de la Membrana/genética , Mutación , Síndrome de Zellweger/genética , ATPasas Asociadas con Actividades Celulares Diversas , Fibroblastos/citología , Fibroblastos/metabolismo , Frecuencia de los Genes , Genotipo , Humanos , Modelos Genéticos , Datos de Secuencia Molecular , Trastorno Peroxisomal/genética , Fenotipo , Polimorfismo Conformacional Retorcido-Simple , Síndrome de Zellweger/patologíaRESUMEN
AIM: Acute peripheral facial palsy due to neuroborreliosis is associated with a distal neuritis. In patients with Lyme disease the activity of antioxidant enzymes is decreased. With respect to the pathogenesis of neuroborreliosis, sera of children with acute peripheral facial palsy were investigated for autoantibodies against human manganese superoxide dismutase (MnSOD), which were suspected of raising the oxidative injury of infected tissues. METHODS: Sera of 20 children with acute peripheral palsy with neuroborreliosis, sera of 20 children with facial palsy without reference to Lyme disease and sera of 14 blood donors were tested for antibodies against human MnSOD using an ELISA. RESULTS: The concentrations of IgM autoantibodies to MnSOD of the children with neuroborreliosis were significantly increased, compared with the two control groups. CONCLUSIONS: We propose that the antibodies detected block the protective effects of MnSOD resulting in an increased oxidative inflammation.
Asunto(s)
Autoanticuerpos/sangre , Parálisis Facial/sangre , Parálisis Facial/inmunología , Neuroborreliosis de Lyme/complicaciones , Superóxido Dismutasa/inmunología , Niño , Echovirus 6 Humano/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Parálisis Facial/etiología , Parálisis Facial/virología , Femenino , Humanos , Neuroborreliosis de Lyme/sangre , Neuroborreliosis de Lyme/inmunología , Masculino , Factores de TiempoRESUMEN
AIM: Children with acute peripheral facial palsy have often suffered tick bites and/or erythema migrans in the head/neck region on the same side. With respect to the pathogenesis of neuroborreliosis this topographical association was investigated in an animal model. METHODS: A Borrelia garinii strain, isolated from the CSF of a child with acute facial palsy, was injected in 9 rats intracutaneously in the right subauricular region. Infected rats were examined for clinical symptoms of Lyme disease, the spread of the spirochetes was investigated by PCR of necropsies (facial nerves, trigeminus nerves, heart, brain, skin) up to 47 days after infection. The nerve tissues were investigated by histology, immunohistochemistry and electron microscopy. RESULTS: None of the rats developed a facial palsy or other symptoms of Lyme disease. Borrelia DNA was found in the heart after 5 days and in the brain after 7 days of infection up to the end of investigation (47 days), as well as in the ipsilateral peripheral nerves after 7 to 33 days. Borrelia was detected by electron microscopy near endoneural vessels of the facial nerve. Peri-, epi-, and endoneural infiltrations of macrophages, plasma cells and B cells characterized an inflammation of the facial and trigeminus nerves ipsilateral to the infection site. CONCLUSION: An infection with Borrelia garinii in the subauricular region induces an ipsilateral neuritis of peripheral nerves. The particular vulnerability of the human facial nerve may be a result of its long intraosseus course. Thus, an inflammatory edema may injure the nerve in the canalis facialis.
Asunto(s)
Grupo Borrelia Burgdorferi , Enfermedades del Nervio Facial/complicaciones , Parálisis Facial/microbiología , Neuroborreliosis de Lyme/complicaciones , Neuritis/complicaciones , Enfermedades del Nervio Trigémino/complicaciones , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Nervio Facial/patología , Enfermedades del Nervio Facial/patología , Parálisis Facial/patología , Neuritis/patología , Ratas , Ratas Wistar , Nervio Trigémino/patología , Enfermedades del Nervio Trigémino/patologíaRESUMEN
The authors investigated the frequency and quantity of intrathecal antibody synthesis against Chlamydia pneumoniae and the presence of C pneumoniae antigen in 25 children with MS. C pneumoniae genome was present in two children. In seven children an intrathecal synthesis of C pneumoniae antibodies was detected, representing only a small part of the total intrathecal immunoglobulin G, suggesting that this intrathecal synthesis is part of a polyspecific, oligoclonal immune response.
Asunto(s)
Anticuerpos Antibacterianos/líquido cefalorraquídeo , Infecciones por Chlamydophila/diagnóstico , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/inmunología , Esclerosis Múltiple/complicaciones , Adolescente , Anticuerpos Antibacterianos/sangre , Especificidad de Anticuerpos , Líquido Cefalorraquídeo/inmunología , Líquido Cefalorraquídeo/microbiología , Niño , Infecciones por Chlamydophila/complicaciones , Chlamydophila pneumoniae/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Masculino , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/microbiología , Bandas Oligoclonales/líquido cefalorraquídeoRESUMEN
Pyruvate kinase (PK) deficiency (PKD) is an autosomal recessive disorder with the typical manifestation of nonspherocytic hemolytic anemia. We analyzed the mutant enzymes of 10 unrelated patients with PKD, whose symptoms ranged from a mild, chronic hemolytic anemia to a severe anemia, by sequence analysis for the presence of alterations in the PKLR gene. In all cases the patients were shown to be compound heterozygous. Eight novel mutations were identified: 458T-->C (Ile153Thr), 656T-->C (Ile219Thr), 877G-->A (Asp293Asn), 991G-->A (Asp331Asn), 1055C-->A (Ala352Asp), 1483G-->A (Ala495Thr), 1649A-->T (Asp550Val), and 183-184ins16bp. This 16 bp duplication produces a frameshift and subsequent stop codon resulting in a drastically reduced mRNA level, and probably in an unstable gene product. Surprisingly, the existence of M2-type PK could be demonstrated in the patient's red blood cells. The study of different polymorphic sites revealed, with one exception, a strict linkage of the 1705C, 1738T, IVS5(+51)T, T(10) polymorphisms and the presence of 14 ATT repeats in intron 11. Our analyses show the consequences of a distorted structure on enzyme function and we discuss the correlations between the mutations identified and the parameters indicative for enzyme function.
Asunto(s)
Anemia Hemolítica Congénita no Esferocítica/genética , Piruvato Quinasa/genética , ARN Mensajero/metabolismo , Alelos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Anemia Hemolítica Congénita no Esferocítica/enzimología , Anemia Hemolítica Congénita no Esferocítica/patología , Secuencia de Bases , ADN/química , ADN/genética , Análisis Mutacional de ADN , Femenino , Genotipo , Haplotipos , Heterocigoto , Humanos , Masculino , Datos de Secuencia Molecular , Mutagénesis Insercional , Mutación , Mutación Puntual , Piruvato Quinasa/deficiencia , ARN Mensajero/genética , Homología de Secuencia de AminoácidoRESUMEN
To determine whether particular Borrelia burgdorferi s.l. genospecies associate solely with rodent reservoir hosts, we compared the genospecies prevalence in questing nymphal Ixodes ticks with that in xenodiagnostic ticks that had fed as larvae on rodents captured in the same site. No genospecies was more prevalent in rodent-fed ticks than in questing ticks. The three main spirochete genospecies, therefore, share common rodent hosts.
Asunto(s)
Grupo Borrelia Burgdorferi/aislamiento & purificación , Reservorios de Enfermedades , Ixodes/microbiología , Muridae/microbiología , Animales , Grupo Borrelia Burgdorferi/clasificación , Grupo Borrelia Burgdorferi/genética , ADN Bacteriano/química , ADN Bacteriano/aislamiento & purificaciónRESUMEN
The occurrence of optic neuropathy in patients with MS-like disorders who carry one of the pathogenetically significant LHON mutations as well as the higher incidence of maternal transmission in familial cases of MS support the hypothesis that mitochondrial genes may be implicated in susceptibility to MS. We sequenced the entire mtDNA of six children with MS who developed optic neuritis as early and prominent visual involvement. The analysis revealed a high degree of nucleotide variations relative to the standard mtDNA sequence. After excluding various synonymous nucleotide changes and common neutral polymorphisms, eight discrete novel missense mutations within the protein coding, tRNA or rRNA genes were detected. None of the eight polymorphic sites were found in common between the patients with MS. Of particular interest was the observation that five of six children carried a total of nine secondary LHON mutations at nucleotide positions 4216, 4917 or 13708. We conclude that variation in mtDNA is unlikely to contribute to genetic predisposition for MS. However, secondary LHON mutations may be regarded as additional risk factor for developing prominent optic nerve involvement. The association of individual sets of mtDNA variations with phenotypic presentation in certain subgroups of MS patients remains to be clarified.
Asunto(s)
ADN Mitocondrial/genética , Predisposición Genética a la Enfermedad/genética , Esclerosis Múltiple/genética , Mutación/genética , Atrofias Ópticas Hereditarias/genética , Neuritis Óptica/genética , Niño , Femenino , Genoma Humano , Humanos , Masculino , Esclerosis Múltiple/complicaciones , Atrofias Ópticas Hereditarias/complicaciones , Neuritis Óptica/etiología , Análisis de Secuencia de ADNRESUMEN
The occurrence of mitochondrial mutations with primary pathogenic significance for Leber's hereditary optic neuropathy in patients with a multiple sclerosis-like phenotype and the preferential maternal transmission points to an involvement of the mitochondrial genome in conferring increased susceptibility to MS. To evaluate the link between MS and mtDNA variations we investigated a total of thirteen children with MS as well as twenty controls by sequencing eight mitochondrial encoded genes which are known to be the loci for LHON-associated mutations. Numerous synonymous nucleotide substitutions and common polymorphisms were excluded from comparative analyses. No primary LHON mutations were found. Secondary LHON mutations were identified more frequently in control subjects than in the children with MS. The remaining eight discrete missense mutations were chosen for further characterization. Only two of them were found in more than one patient. Our results suggest that nucleotide substitutions within the ND1, ND2, ND4, ND5, ND6, COI, COIII or cytochrome b genes of mtDNA do not contribute to the etiology of typical MS. However, the association of LHON mutations with visual impairment in MS as well as the relationship between phenotypic diversity in certain subgroups of patients with individual mtDNA genotypes merits further investigations.
Asunto(s)
ADN Mitocondrial/genética , Esclerosis Múltiple/genética , Mutación Missense/genética , Atrofias Ópticas Hereditarias/genética , Trastornos de la Visión/genética , Adolescente , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad/genética , Genoma Humano , Humanos , Masculino , Neuritis Óptica/genética , Fenotipo , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
The higher maternal transmission of multiple sclerosis in familial cases and the coincidence of a MS-like phenotype with mitochondrial point mutations in patients with Leber's hereditary optic neuropathy has inspired a detailed assessment of the mitochondrial genome as an etiological factor in the pathogenesis of MS. To further elucidate the contribution of maternally transmitted mutations to MS susceptibility, we sequenced five protein- and all RNA-coding genes of the mtDNA from thirteen children with MS and twenty unaffected individuals. After excluding several synonymous mutations and common polymorphisms, a total of ten ambiguous missense or protein synthesis mutations were selected and analysed. By defining minimal criteria for pathogenity--incidence, location and degree of evolutionary conservation--we conclude that sequence variations in COII, ATPase6 and 8, ND3, or ND4L subunits of oxidative phosphorylation as well as in rRNA and tRNA genes are unlikely to increase susceptibility for the development of MS.
Asunto(s)
ADN Mitocondrial/genética , Distrofias Musculares/genética , Mutación Missense/genética , Trastornos de la Visión/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad/genética , Genoma Humano , Humanos , Masculino , Encefalomiopatías Mitocondriales/genética , Atrofias Ópticas Hereditarias/genética , Neuritis Óptica/genética , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genética , ARN/genética , Análisis de Secuencia de ADNRESUMEN
This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.
Asunto(s)
Mutación , Proteínas de Neoplasias/genética , Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogénicas/genética , Dedos de Zinc/genética , Secuencia de Aminoácidos , Secuencia de Bases , Southern Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Expresión Génica , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Datos de Secuencia Molecular , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , Mutación Puntual , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-mdm2 , Células Tumorales CultivadasRESUMEN
To determine whether Norway rats contribute to the risk of human Lyme disease in a central European city park, densities of endemic rodents were compared as were feeding densities of vector ticks and prevalence of infection by the Lyme disease spirochete. Only Norway rats and yellow-necked mice were abundant, and three times as many mice as rats were present. More larval ticks fed on rats than on mice, and far more nymphs engorged on the rats. All rats but only about half of the mice infected ticks. Each rat was more infectious than each infectious mouse. Infected rats were distributed throughout the city. Spirochetes infected about a quarter of the questing nymphal ticks. The capacity of rats to serve as reservoir hosts for the Lyme disease spirochete, therefore, increases risk of infection among visitors to this and other urban parks.
Asunto(s)
Reservorios de Enfermedades , Ixodes/microbiología , Enfermedad de Lyme/etiología , Ratas/parasitología , Animales , Humanos , Enfermedad de Lyme/transmisión , Muridae/parasitología , RiesgoRESUMEN
Spirochete diversity in acrodermatitis chronica atrophicans lesions in a closely defined central European site was compared to that in the local vector population, in human erythema migrans lesions, and in cerebrospinal fluid by amplifying and sequencing a segment of the gene of outer surface protein A directly from sampled tissues. Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi acutely infect human skin and invade internal tissues. Only B. afzelii, however, is associated with acrodermatitis chronica atrophicans lesions, persisting chronically where the skin has atrophied.
Asunto(s)
Acrodermatitis/etiología , Acrodermatitis/microbiología , Infecciones por Borrelia/microbiología , Borrelia/clasificación , Lipoproteínas , Enfermedad de Lyme/microbiología , Acrodermatitis/epidemiología , Animales , Antígenos de Superficie/genética , Proteínas de la Membrana Bacteriana Externa/genética , Vacunas Bacterianas , Borrelia/genética , Borrelia/aislamiento & purificación , Infecciones por Borrelia/complicaciones , Infecciones por Borrelia/epidemiología , Alemania/epidemiología , Humanos , Enfermedad de Lyme/complicaciones , Enfermedad de Lyme/epidemiología , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Garrapatas/microbiologíaRESUMEN
To determine whether the characteristics of the Lyme disease spirochete (Borrelia burgdorferi) in Europe may have changed during the past century, DNA was amplified from archived Ixodes ricinus ticks. Tick DNA could be amplified, even when ticks had been stored under museum conditions for nearly a century. Spirochetal DNA was detected by polymerase chain reaction in 6 ticks preserved for as long as a century; the oldest was collected in 1884. Borrelia garinii, which predominates in modern ticks in the region, infected 3 of these older ticks, and the presently infrequent B. burgdorferi sensu stricto infected 2. These data indicate that residents of Europe have been exposed to diverse Lyme disease spirochetes at least since 1884, concurrent with the oldest record of apparent human infection.