RESUMEN
The Fragile Mental Retardation 1 gene (FMR1), at Xq27.3, encodes the fragile mental retardation protein (FMRP), and displays in its 5'-untranslated region a series of polymorphic CGG triplet repeats that may undergo dynamic mutation. Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability among men, and is most frequently due to FMR1 full mutation and consequent transcription repression. FMR1 premutations may associate with at least two other clinical conditions, named fragile X-associated primary ovarian insufficiency (FXPOI) and tremor and ataxia syndrome (FXTAS). While FXPOI and FXTAS appear to be mediated by FMR1 mRNA accumulation, relative reduction of FMRP, and triplet repeat translation, FXS is due to the lack of the RNA-binding protein FMRP. Besides its function as mRNA translation repressor in neuronal and stem/progenitor cells, RNA editing roles have been assigned to FMRP. In this review, we provide a brief description of FMR1 transcribed microsatellite and associated clinical disorders, and discuss FMRP molecular roles in ribonucleoprotein complex assembly and trafficking, as well as aspects of RNA homeostasis affected in FXS cells.
Asunto(s)
Ataxia/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Homeostasis/genética , Insuficiencia Ovárica Primaria/genética , ARN/metabolismo , Ribonucleoproteínas/genética , Temblor/genética , Ataxia/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/genética , Citoplasma/metabolismo , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/metabolismo , Humanos , Masculino , Mutación , Insuficiencia Ovárica Primaria/metabolismo , ARN/genética , Edición de ARN , Ribonucleoproteínas/metabolismo , Temblor/metabolismoAsunto(s)
Ataxia/diagnóstico por imagen , Síndrome del Cromosoma X Frágil/diagnóstico por imagen , Enfermedades de Inicio Tardío/diagnóstico por imagen , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Temblor/diagnóstico por imagen , Anciano de 80 o más Años , Ataxia/complicaciones , Ataxia/genética , Femenino , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/genética , Humanos , Enfermedades de Inicio Tardío/complicaciones , Enfermedades de Inicio Tardío/genética , Masculino , Persona de Mediana Edad , Parálisis Supranuclear Progresiva/complicaciones , Parálisis Supranuclear Progresiva/genética , Temblor/complicaciones , Temblor/genéticaAsunto(s)
Ataxia/diagnóstico , Síndrome del Cromosoma X Frágil/diagnóstico , Temblor/diagnóstico , Adulto , Edad de Inicio , Ataxia/genética , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Humanos , Masculino , Sensibilidad y Especificidad , Temblor/genéticaRESUMEN
Abstract Introduction: The FMR1 gene has four allelic variants according to the number of repeats of the CGG triplet. Premutation carriers with between 55 and 200 repeats are susceptible to developing pathologies such as tremor and ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) syndrome. Case description: The patient was a 53-year-old female farmer with severe tremor in the upper limbs at rest that worsens with movement, tremor in the jaw and tongue, and generalized cerebral atrophy. She is a carrier of the FMR1 premutation diagnosed by PCR and Southern Blot, complying with the clinical and radiological criteria of FXTAS, and in addition, has a history of vagal symptoms suggestive of ovarian failure and menstrual cycle disorders that led to hysterectomy at age 33 and was subsequently diagnosed with FXPOI. Conclusion: An unusual case of FXTAS and FXPOI complying with clinical and radiological criteria is reported in a premutation carrier of the FMR1 gene.
Resumen Introducción: el gen FMR1 tiene cuatro variantes alélicas según el número de repeticiones de la tripleta CGG. Los portadores de la premutación con un número entre 55 y 200 repeticiones son susceptibles de desarrollar patologías como el síndrome de temblor y ataxia (FXTAS) y síndrome de falla ovárica prematura (FXPOI) asociados al X frágil. Descripción del caso: Mujer de 53 años, agricultora, con temblor severo en miembros superiores en reposo que empeora con el movimiento, temblor en mandíbula y lengua, atrofia cerebral generalizada, portadora de la premutación del gen FMR1 diagnosticada por PCR y Southern Blot, cumpliendo con criterios clínicos y radiológicos de FXTAS; ademas, historia de síntomas vagales sugestivos de falla ovárica y trastornos del ciclo menstrual que llevaron a histerectomía a los 33 años, haciendose diagnóstico FXPOI. Conclusión: Se reporta un caso inusual en portadoras de la premutación del gen FMR1, con criterios clínicos y radiológicos de FXTAS y FXPOI.
Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Ataxia/genética , Temblor/genética , Insuficiencia Ovárica Primaria/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Southern Blotting , Reacción en Cadena de la Polimerasa , Repeticiones de Trinucleótidos/genética , AlelosRESUMEN
BACKGROUND: Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. DEVELOPMENT: This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). CONCLUSIONS: Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments.
Asunto(s)
Ataxia/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/farmacología , Síndrome del Cromosoma X Frágil/genética , Temblor/genética , Ataxia/diagnóstico , Trastorno Autístico , Síndrome del Cromosoma X Frágil/diagnóstico , Humanos , Discapacidad Intelectual , Mutación/genética , ARN Mensajero , Temblor/diagnósticoRESUMEN
INTRODUCTION: The FMR1 gene has four allelic variants according to the number of repeats of the CGG triplet. Premutation carriers with between 55 and 200 repeats are susceptible to developing pathologies such as tremor and ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) syndrome. CASE DESCRIPTION: The patient was a 53-year-old female farmer with severe tremor in the upper limbs at rest that worsens with movement, tremor in the jaw and tongue, and generalized cerebral atrophy. She is a carrier of the FMR1 premutation diagnosed by PCR and Southern Blot, complying with the clinical and radiological criteria of FXTAS, and in addition, has a history of vagal symptoms suggestive of ovarian failure and menstrual cycle disorders that led to hysterectomy at age 33 and was subsequently diagnosed with FXPOI. CONCLUSION: An unusual case of FXTAS and FXPOI complying with clinical and radiological criteria is reported in a premutation carrier of the FMR1 gene.
INTRODUCCIÓN: el gen FMR1 tiene cuatro variantes alélicas según el número de repeticiones de la tripleta CGG. Los portadores de la premutación con un número entre 55 y 200 repeticiones son susceptibles de desarrollar patologías como el síndrome de temblor y ataxia (FXTAS) y síndrome de falla ovárica prematura (FXPOI) asociados al X frágil. DESCRIPCIÓN DEL CASO: Mujer de 53 años, agricultora, con temblor severo en miembros superiores en reposo que empeora con el movimiento, temblor en mandíbula y lengua, atrofia cerebral generalizada, portadora de la premutación del gen FMR1 diagnosticada por PCR y Southern Blot, cumpliendo con criterios clínicos y radiológicos de FXTAS; ademas, historia de síntomas vagales sugestivos de falla ovárica y trastornos del ciclo menstrual que llevaron a histerectomía a los 33 años, haciendose diagnóstico FXPOI. CONCLUSIÓN: Se reporta un caso inusual en portadoras de la premutación del gen FMR1, con criterios clínicos y radiológicos de FXTAS y FXPOI.
Asunto(s)
Ataxia/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Insuficiencia Ovárica Primaria/genética , Temblor/genética , Alelos , Southern Blotting , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Repeticiones de Trinucleótidos/genéticaAsunto(s)
Ataxia/terapia , Estimulación Encefálica Profunda/métodos , Síndrome del Cromosoma X Frágil/terapia , Núcleos Talámicos Posteriores , Temblor/terapia , Zona Incerta , Anciano , Ataxia/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Humanos , Masculino , Resultado del Tratamiento , Temblor/genéticaRESUMEN
Carriers of an FMR1 premutation allele (55-200 CGG repeats) often develop the neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS). Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline have not been reported in individuals with an unmethylated full mutation (FM). Here, we report a Chilean family affected with FXS, inherited from a parent carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast progressing FXTAS. This case suggests that the definition of FXTAS may need to be broadened to not only include those with a premutation but also those with an expanded allele in FM range with a lack of methylation leading to elevated FMR1-mRNA expression levels and subsequent RNA toxicity.
Asunto(s)
Ataxia/genética , Metilación de ADN/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Temblor/genética , Anciano , Ataxia/complicaciones , Ataxia/patología , Chile , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/patología , Humanos , Masculino , Mosaicismo , Temblor/complicaciones , Temblor/patologíaRESUMEN
FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.
Asunto(s)
Ataxia , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil , Temblor , Animales , Ataxia/diagnóstico , Ataxia/tratamiento farmacológico , Ataxia/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Temblor/diagnóstico , Temblor/tratamiento farmacológico , Temblor/genéticaRESUMEN
FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.
A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.
Asunto(s)
Animales , Humanos , Masculino , Persona de Mediana Edad , Ataxia , Síndrome del Cromosoma X Frágil , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Temblor , Ataxia/diagnóstico , Ataxia/tratamiento farmacológico , Ataxia/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/genética , Imagen por Resonancia Magnética , Temblor/diagnóstico , Temblor/tratamiento farmacológico , Temblor/genéticaRESUMEN
We studied the association between polymorphisms of genes coding for dopamine D(2) (DRD2), dopamine D(3) (DRD3), serotonin 2(a) (HTR2A), and serotonin 2(c) (HTR2C) receptors and Antipsychotic-Induced Parkinsonism (AIP), rigidity, bradykinesia, and rest-tremor in African-Caribbeans treated with antipsychotics. Polymorphisms of DRD2 (-141CIns/Del, TaqIA, 957C > T), DRD3 (Ser9Gly), HTR2A (-1438A > G, 102T > C, His452Tyr), and HTR2C (-759C > T, Cys23Ser) genes were determined according to standard protocols. The Unified Parkinson Disease Rating Scale was used for the measurement of AIP, rigidity, bradykinesia, and rest-tremor. Chi-squared or Fisher's exact tests were applied for the association analyses. The t-test was applied for continuous data. Ninety nine males and 27 females met the inclusion criteria (Schizophr Res 1996, 19:195). In males, but not in females, there were significant associations between -141CDel-allele carriership (DRD2) and rigidity (Fisher's Exact Test: P = 0.021) and between 23Ser-allele carriership (HTR2C) and bradykinesia (P = 0.026, chi(2) = 5.0) or AIP (P = 0.008, chi(2) = 7.1). Rest-tremor was not associated with any of the polymorphisms studied. Analyses of the age, chlorpromazine equivalents, benztropine equivalents, the number of patients using anticholinergic medication, and the utilization patterns of the antipsychotic medication did not show statistically significant differences between patients with and without AIP, rigidity, bradykinesia, rest-tremor. Conducting the analysis without gender stratification did not affect our findings considerably, except for the association between bradykinesia and 23Ser-allele which failed to reach statistical significance in the total sample (P = 0.0646, chi(2) = 3.41). Since AIPs subsymptoms (rigidity, bradykinesia, and rest-tremor) may differ pharmacogenetically, our data strongly support symptom-specific analysis of AIP. However, further research is warranted to confirm our findings.
Asunto(s)
Población Negra/genética , Hipocinesia/genética , Rigidez Muscular/genética , Trastornos Parkinsonianos/genética , Receptores Dopaminérgicos/genética , Receptores de Serotonina/genética , Temblor/genética , Adulto , Anciano , Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico , Resistencia a Medicamentos/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Hipocinesia/tratamiento farmacológico , Pacientes Internos , Masculino , Persona de Mediana Edad , Rigidez Muscular/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Farmacogenética , Temblor/tratamiento farmacológico , Indias Occidentales/etnologíaRESUMEN
A late onset neurological syndrome in carriers of premutation in FMR1 gene was recently described. The condition was named fragile-X-associated tremor/ataxia syndrome (FXTAS) and includes intentional tremor, cerebellar ataxia, parkinsonism, and cognitive deficit. We ascertained the contribution of FMR1 premutation to the phenotypes ataxia, tremor and/or parkinsonism. Sixty-six men over 45 years old presenting these symptoms, isolated or combined, were tested. Also, 74 normal men, randomly chosen in the population, formed the control group. In the patient group, no premutation carrier was found, which is in agreement with other observed frequencies reported elsewhere (0-5% variation). No significant differences were found when comparing gray zone allele frequencies among target and control groups. The FXTAS contribution in patients with phenotypic manifestations of FXTAS was 15/748 (2%). The presence of gray zone alleles is not correlated with FXTAS occurrence.
Asunto(s)
Ataxia , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Frecuencia de los Genes , Temblor , Alelos , Ataxia/diagnóstico , Ataxia/genética , Ataxia/patología , Ataxia/fisiopatología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Temblor/diagnóstico , Temblor/genética , Temblor/patología , Temblor/fisiopatologíaAsunto(s)
Colestanotriol 26-Monooxigenasa/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Xantomatosis Cerebrotendinosa/diagnóstico , Xantomatosis Cerebrotendinosa/genética , Adolescente , Argentina , Encéfalo/enzimología , Encéfalo/patología , Encéfalo/fisiopatología , Colestanol/sangre , Colesterol/metabolismo , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Discapacidad Intelectual/enzimología , Discapacidad Intelectual/genética , Discapacidad Intelectual/fisiopatología , Imagen por Resonancia Magnética , Masculino , Mitocondrias/enzimología , Mitocondrias/genética , Temblor/enzimología , Temblor/genética , Temblor/fisiopatología , Xantomatosis Cerebrotendinosa/fisiopatologíaRESUMEN
A late onset neurological syndrome in carriers of premutation in FMR1 gene was recently described. The condition was named fragile-X-associated tremor/ataxia syndrome (FXTAS) and includes intentional tremor, cerebellar ataxia, parkinsonism, and cognitive deficit. We ascertained the contribution of FMR1 premutation to the phenotypes ataxia, tremor and/or parkinsonism. Sixty-six men over 45 years old presenting these symptoms, isolated or combined, were tested. Also, 74 normal men, randomly chosen in the population, formed the control group. In the patient group, no premutation carrier was found, which is in agreement with other observed frequencies reported elsewhere (0-5% variation). No significant differences were found when comparing gray zone allele frequencies among target and control groups. The FXTAS contribution in patients with phenotypic manifestations of FXTAS was 15/748 (2%). The presence of gray zone alleles is not correlated with FXTAS occurrence.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Ataxia/diagnóstico , Enfermedad de Parkinson/diagnóstico , Frecuencia de los Genes , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Temblor/diagnóstico , Alelos , Ataxia/fisiopatología , Ataxia/genética , Ataxia/patología , Estudios de Casos y Controles , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Predisposición Genética a la Enfermedad , Temblor/fisiopatología , Temblor/genética , Temblor/patologíaRESUMEN
In 1989, we described a new autosomic-recessive myelin-mutant rat that develops a progressive motor syndrome characterized by tremor, ataxia, immobility episodes (IEs), epilepsy, and paralysis. taiep is the acronym of these symptoms. The rat developed a hypomyelination, followed by demyelination. At an age of 7-8 months, taiep rats developed IEs, characterized electroencephalographically by REM sleep-like cortical activity. In our study, we analyzed the ontogeny of gripping-induced IEs between 5 and 18 months, their dependence to light-dark changes, sexual dimorphism, and susceptibility to mild stress. Our results showed that IEs start at an age of 6.5 months, with a peak frequency between 8.5 and 9.5 months. IEs have two peaks, one in the morning (0800-1000 h) and a second peak in the middle of the night (2300-0100 h). Spontaneous IEs showed an even distribution with a mean of 3 IEs every 2 h. IEs are sexually dimorphic being more common in male rats. The IEs can be induced by gripping the rat by the tail or the thorax, but most of the IEs were produced by gripping the tail. Mild stress produced by i.p. injection of physiological saline significantly decreased IEs. These results suggested that IEs are dependent on several biological variables, which are caused by hypomyelination, followed by demyelization, which causes alterations in the brainstem and hypothalamic mechanisms responsible for the sleep-wake cycle regulation, producing emergence of REM sleep-like behavior during awake periods.
Asunto(s)
Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/fisiopatología , Trastornos del Movimiento/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Factores de Edad , Animales , Tronco Encefálico/patología , Tronco Encefálico/fisiopatología , Cataplejía/genética , Cataplejía/patología , Cataplejía/fisiopatología , Corteza Cerebral/fisiopatología , Trastornos de la Conciencia/genética , Trastornos de la Conciencia/patología , Trastornos de la Conciencia/fisiopatología , Epilepsia/genética , Epilepsia/patología , Epilepsia/fisiopatología , Femenino , Predisposición Genética a la Enfermedad/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/patología , Hipotálamo/patología , Hipotálamo/fisiopatología , Masculino , Trastornos del Movimiento/genética , Trastornos del Movimiento/patología , Narcolepsia/genética , Narcolepsia/patología , Narcolepsia/fisiopatología , Ratas , Ratas Mutantes , Caracteres Sexuales , Parálisis del Sueño/genética , Parálisis del Sueño/patología , Parálisis del Sueño/fisiopatología , Trastornos del Sueño-Vigilia/genética , Trastornos del Sueño-Vigilia/patología , Estrés Psicológico/genética , Estrés Psicológico/patología , Estrés Psicológico/fisiopatología , Temblor/genética , Temblor/patología , Temblor/fisiopatologíaRESUMEN
AIM: To present the latest findings on fragile X syndrome, the first genetic disorder identified to be caused by a new type of mutation called trinucleotide repeat expansion. DEVELOPMENT: Fragile X syndrome is the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the FMR1 gene. In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica. The second section deals with the recent findings in relation to the very recently described fragile X premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting carriers of the mutation. CONCLUSIONS: Screening for the gene premutation in aged individuals who have tremor and balance problems is important, especially when accompanied by other signs such as parkinsonism, short term memory loss and dementia. Family genetic counselling can help those affected as well as future generations which may inherit fragile X syndrome.
Asunto(s)
Ataxia/complicaciones , Ataxia/genética , Encéfalo/fisiopatología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/genética , Proteínas del Tejido Nervioso/genética , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/genética , Proteínas de Unión al ARN/genética , Temblor/complicaciones , Temblor/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Frecuencia de los Genes/genética , Humanos , Imagen por Resonancia Magnética , Trastornos de la Memoria/etiología , Memoria a Corto Plazo , Fenotipo , Mutación Puntual/genética , Repeticiones de Trinucleótidos/genéticaRESUMEN
Reactive astrocytosis in taiep rats was shown by glial fibrillary acidic protein (GFAP) immunoreactivity measured by means of enzyme-linked immunosorbent assay and indirect immunofluorescence. Increased GFAP immunoreactivity was first observed in the brainstem of 15-day-old taiep rats and was widespread throughout all brain regions at 6 months of age. Characteristically, astrocytes were hypertrophic and displayed strong GFAP fluorescence. The pattern of these reactive cells may correlate with the process of dysmyelination in the taiep rat.
Asunto(s)
Encéfalo/patología , Enfermedades Desmielinizantes/genética , Gliosis/genética , Animales , Astrocitos/química , Astrocitos/patología , Ataxia/genética , Biomarcadores , Enfermedades Desmielinizantes/patología , Progresión de la Enfermedad , Retículo Endoplásmico Liso/patología , Ensayo de Inmunoadsorción Enzimática , Epilepsia Refleja/genética , Técnica del Anticuerpo Fluorescente Indirecta , Proteína Ácida Fibrilar de la Glía/análisis , Gliosis/patología , Hipertrofia , Microtúbulos/patología , Ratas , Ratas Mutantes , Ratas Sprague-Dawley , Convulsiones/genética , Temblor/genéticaAsunto(s)
Mentón , Mioclonía/genética , Temblor/genética , Electromiografía , Femenino , Humanos , Persona de Mediana Edad , Mioclonía/diagnóstico , Linaje , Temblor/diagnósticoRESUMEN
El temblor esencial (TE) es el más común de los desórdenes del movimiento, afectado a cerca del 5 por ciento de las personas mayores de 40 años. Se le considera un trastorno genético transmitido en forma autosómico-dominante con fenómeno de anticipación, describiéndose también formas esporádicas. Debido a que tradicionalmente se le señala como un trastorno benigno y monosintomático, es poco diagnosticado lo cual priva a los afectados de los beneficios de una terapia oportuna. Estudios recientes han mostrado que un 15 por ciento de los pacientes con TE se jubilan tempranamente debido al temblor y hasta un 5 por ciento de los afectados se ven tan incapacitados que dependen en gran medida de sus familiares para sus actividades cotidianas. La relación del temblor con otros desórdenes del movimiento como las distonías y la enfermedad de Parkinson es controversial aceptándose actualmente que solo un porcentaje pequeño de los pacientes con TE desarrollarán dichos padecimientos ya que los estudios que señalaron al temblor como un importante antecedente para las distonias y el Parkinson, no contaron con criterios clínicos adecuados. El tratamiento del TE está basado en el grado de afectación, aconsejándose una terapia a largo plazo sólo en los sujetos en que el temblor interfiera notoriamente en actividades diarias. Los medicamentos más utilizados son el propanolol y la primodina. La cirugía estereotáctica se ha empleado con éxito en sujetos con temblores incapacitantes con nula respuesta a la medicación. En esta revisión se hace hincapié en los criterios diagnósticos, tratamiento y relación del TE con otros trastornos del movimiento
Asunto(s)
Humanos , Distonía/complicaciones , Distonía/congénito , Temblor/clasificación , Temblor/diagnóstico , Temblor/genética , Temblor/terapiaRESUMEN
Revisamos os registros de 176 pacientes com tremor essencial (TE) quanto à história familiar, características do tremor, distribuiçäo anatômica, idade de início dos sintomas. Os pacientes foram divididos em dois grupos: familiar (F) e näo familiar (NF). História familiar de tremor foi encontrada em 47,2 por cento da amostra. O tremor de açäo e postura ocorreu combinadamente em 49.4 por cento, somente de postura em 26,7 por cento e somente de açäo em 9.1 por cento. O tremor de repouso foi registrado em 10.2 por cento, sempre associado a outras características. Näo houve diferenças clínicas entre os grupos F e NF. As mäos foram acometidas em 94.9 por cento e a cabeça em 26.5 por cento. O acometimento isolado das mäos foi mais frequente no sexo masculino, enquanto o tremor de cabeça foi mais frequente no sexo feminino. A idade de início variou de 4 a 85 anos e se mostrou significantemente menor nos pacientes do sexo masculino com história familiar (36,5 por cento) e também nos pacientes do sexo masculino com tremor de açäo e postura combinados. A idade de início näo foi diferente quando se compararam grupos de pacientes com a mäe ou o pai acometidos. Embora existam diferenças nesta amostra, elas näo säo suficientes para considerar o TE familiar e o näo familiar como entidades distintas