RESUMEN
BACKGROUND: The Department of Veterans Affairs (VA) Cooperative Studies Program has established a National Registry of Veterans with Amyotrophic Lateral Sclerosis (ALS). This article describes the objectives, methods, and sample involved in the registry. METHODS: United States military veterans with ALS were identified through national VA electronic medical record databases and nationwide publicity efforts for an enrollment period of 4 1/2 years. Diagnoses were confirmed by medical record reviews. Registrants were asked to participate in a DNA bank. Follow-up telephone interviews are conducted every 6 months to track participants' health status. RESULTS: As of September 30, 2007, 2,400 veterans had consented to participate in the registry, 2,068 were included after medical record review, 995 were still living and actively participating, and 1,573 consented to participate in the DNA bank. 979 participants had been enrolled in the registry for at least 1 year, 497 for at least 2 years, and 205 for at least 3 years. Fourteen studies have been approved to use registry data for epidemiological, observational, and interventional protocols. CONCLUSION: This registry has proven to be a successful model for identifying large numbers of patients with a relatively rare disease and enrolling them into multiple studies, including genetic protocols.
Asunto(s)
Esclerosis Amiotrófica Lateral/epidemiología , Bases de Datos como Asunto/organización & administración , Sistema de Registros , Veteranos/estadística & datos numéricos , Adulto , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/terapia , Femenino , Humanos , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiologíaRESUMEN
The Charcot-Marie-Tooth (CMT) neuropathies are a group of disorders exhibiting neurophysical, pathological and genetic heterogeneity. CMT2 is a diagnostic subtype of this group of disorders characterized by variable expression and age-of-onset and normal or slightly diminished nerve conduction velocities. Previously, linkage and heterogeneity had been reported in CMT2 with linked families localizing to chromosome 1p (CMT2A). Recently a second CMT2 locus has been described on chromosome 7 in a single large CMT2 family (CMT2D). We have performed pedigree linkage analysis on 15 CMT2 families (N = 371 individuals, 106 affected family members) and have confirmed linkage to chromosome 7. Furthermore, using both admixture and multipoint linkage analysis we show conclusive evidence for additional heterogeneity within this clinical subtype with evidence of families that exclude linkage to both the CMT2D and CMT2A regions. In addition, unlike the previous report we found no obvious consistent clinical differences between the linked family types.
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Enfermedad de Charcot-Marie-Tooth/genética , Cromosomas Humanos Par 7/genética , Mapeo Cromosómico , ADN/genética , Salud de la Familia , Femenino , Heterogeneidad Genética , Ligamiento Genético , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , LinajeRESUMEN
Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. We have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analysis and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the "linked" families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.
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Enfermedad de Charcot-Marie-Tooth/genética , Cromosomas Humanos Par 1 , Adulto , Factores de Edad , Alelos , Mapeo Cromosómico , ADN/sangre , ADN/genética , ADN/aislamiento & purificación , Femenino , Frecuencia de los Genes , Ligamiento Genético , Humanos , Leucocitos/metabolismo , Escala de Lod , Linfocitos/metabolismo , Masculino , Linaje , ProbabilidadRESUMEN
Vertebral disc space infection is an uncommon cause of back pain. Physical findings may be unimpressive and laboratory evaluation may only disclose an elevated erythrocyte sedimentation rate. Magnetic resonance imaging is particularly useful, since it reveals abnormalities earlier than plain radiographs and is more precise than bone scan.
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Discitis/diagnóstico , Imagen por Resonancia Magnética , Dolor de Espalda/etiología , Discitis/microbiología , Humanos , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Osteomielitis/diagnóstico , Osteomielitis/microbiología , Infecciones Estafilocócicas/diagnósticoAsunto(s)
Neoplasias Encefálicas/diagnóstico , Meningioma/diagnóstico , Paraparesia Espástica Tropical/diagnóstico , Neoplasias Encefálicas/complicaciones , Electromiografía , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Imagen por Resonancia Magnética , Meningioma/complicaciones , Persona de Mediana Edad , Paraparesia Espástica Tropical/etiologíaRESUMEN
The existence of an X-linked sensorimotor peripheral neuropathy has been debated. We reevaluated the original family, and present data on 13 affected males and 25 obligate or probable heterozygous females, documenting the devastating nature of the disease in the men and the extremely variable degree of clinical involvement in the carriers. Use of DNA probes indicates that the gene lies in the DXYS1-p58-1 region of the X-chromosome.
Asunto(s)
Ligamiento Genético , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Atrofia Muscular/genética , Cromosoma X , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Marcadores Genéticos , Neuropatías Hereditarias Sensoriales y Autónomas/fisiopatología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Conducción Nerviosa , LinajeRESUMEN
Following a 15-foot fall from a roof, a 70-year-old man became comatose and developed signs of pontine dysfunction. There was a severely comminuted fracture of the distal left femur suggesting that he had landed in an upright position. It was clinically unclear whether the fall was secondary to a pontine infarct; however, an autopsy revealed a fracture of the clivus which had entrapped and occluded the basilar artery, causing death. These findings, and those in similar cases, suggest that this entity results from a force transmitted in an axial direction.