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1.
Rev. chil. endocrinol. diabetes ; 10(4): 142-149, oct. 2017. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-999021

RESUMO

Puberty is a period of transition during which girls and boys acquire secondary sexual characteristics and reproductive capacity. The order of appearance of the pubertal traits accounts for a correct or otherwise incorrect activation of the hypothalamic-pituitary-gonadal axis. The growth of the pubic hair before 8 years in girls and 9 years in boys (precocious pubarche, PP) without any other apparent cause has been largely attributed to the early increase of adrenal androgen levels. Also, premature adrenarche (PA) was traditionally considered an extreme within the normal range, however emerging evidence links early androgen excess with the metabolic syndrome. In this context, it has been suggested that an exacerbated clinical manifestation of androgens may be related to greater sensitivity of the androgen receptor (AR). The purpose of this review is to summarize the current knowledge of the contribution of the CAG repeats polymorphisms of AR in the peripubertal manifestations of androgens with special emphasis on precocious pubarche and body composition


Assuntos
Humanos , Masculino , Polimorfismo Genético , Puberdade Precoce/genética , Receptores Androgênicos/genética , Repetições de Trinucleotídeos , Composição Corporal , Adrenarca/genética
4.
Braz. j. med. biol. res ; 46(8): 722-727, ago. 2013. tab, graf
Artigo em Inglês | LILACS | ID: lil-684526

RESUMO

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.


Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doença de Huntington/metabolismo , Espectroscopia de Ressonância Magnética , Doenças Talâmicas/metabolismo , Tálamo/fisiopatologia , Ácido Aspártico/análise , Ácido Aspártico/análogos & derivados , Estudos de Casos e Controles , Creatina/análise , Deutério , Dipeptídeos/análise , Glicerilfosforilcolina/análise , Atividade Motora , Fosfocreatina/análise , Fosforilcolina/análise , Repetições de Trinucleotídeos , Doenças Talâmicas/diagnóstico
6.
Electron. j. biotechnol ; 13(6): 5-6, Nov. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-591909

RESUMO

Cultivated peanut (Arachis hypogaea L.) is an oilseed crop of economic importance. It is native to South America, and it is grown extensively in the semi-arid tropics of Asia, Africa, and Latin America. Given an extremely narrow genetic base, efforts are being made to develop simple sequence repeat (SSR) markers to provide useful genetic and genomic tools for the peanut research community. A SSR-enriched library to isolate trinucleotide (GGC)n SSRs in peanut was constructed. A total of 143 unique sequences containing (GGC)n repeats were identified. One hundred thirty eight primer pairs were successfully designed at the flanking regions of SSRs. A suitable polymerase was chosen to amplify these GC-rich sequences. Although a low level of polymorphism was observed in cultivated peanut by these new developed SSRs, a high level of transferability to wild species would be beneficial to increasing the number of SSRs in wild species.


Assuntos
Arachis/genética , Repetições de Microssatélites , DNA de Plantas/genética , Cultivos Agrícolas , Marcadores Genéticos , Polimorfismo Genético , Repetições de Trinucleotídeos
7.
Gac. méd. Méx ; 144(5): 413-418, sept.-oct. 2008. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: lil-568030

RESUMO

Antecedentes: La ataxia espinocerebelosa tipo 2 es causada por la expansión del repetido CAG presente en el exón 1 del gen de la ataxina-2, lo cual origina la incorporación de un segmento de poliglutaminas en la proteína mutante. Métodos: Mediante reacción en cadena de la polimerasa y electroforesis capilar se determinó el número de repetidos CAG del gen de la ataxina-2 en 66 individuos pertenecientes a tres familias mexicanas diagnosticadas clínicamente con ataxia espinocerebelosa tipo 2, y en 400 individuos de una muestra de población mestiza mexicana. Resultados: Se identificó la expansión del repetido CAG en 11 sujetos con sintomatología de ataxia espinocerebelosa tipo 2 y en cuatro individuos asintomáticos, lo que confirmó el diagnóstico en dos de las tres familias analizadas. Se determinó que los pacientes con mayor número de repetidos desarrollaron la sintomatología de la enfermedad a una edad más temprana, fenómeno conocido como “anticipación”. Los alelos silvestres presentaron un rango entre 13 y 30 repetidos CAG, siendo el alelo de 22 repetidos el más frecuente, mientras que los alelos mutados mostraron un rango de 36 a 54 repetidos. Conclusiones: La identificación de la expansión del repetido CAG del gen de la ataxina-2 confirmó el diagnóstico clínico de ataxia espinocerebelosa tipo 2.


BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) results from the expansion of a CAG triplet located within the coding sequence of the ataxin-2 gene, which ultimately provokes the incorporation of a stretch of polyglutamines in the mutant protein. METHODS: We determined by PCR and capillary electrophoresis the number of ataxin2 gene CAG repeats in 66 individuals belonging to 3 families, clinically diagnosed with SCA2, and 400 subjects from a sample of the mestizo Mexican population. RESULTS: The CAG repeat expansion was found in 11 symptomatic subjects and four asymptomatic individuals, confirming the SCA2 clinical diagnosis in two out of the three families studied. We noted that patients with longer CAG repeat numbers have an early disease onset, a phenomenon known as anticipation. Wild-type alleles showed a CAG repeat range between 13 and 30, and the allele carrying 22 CAG repeats was the most common among our sample. Mutant alleles also displayed a range between 36 and 54 CAG repeats. CONCLUSIONS: The identification of the CAG repeat expansion facilitates an accurate SCA2 diagnosis.


Assuntos
Humanos , Adolescente , Adulto Jovem , Ataxias Espinocerebelares/genética , Proteínas do Tecido Nervoso/genética , Repetições de Trinucleotídeos , México , Linhagem
8.
Genet. mol. res. (Online) ; 7(1): 43-49, Jan. 2008. tab, ilus
Artigo em Inglês | LILACS | ID: lil-553769

RESUMO

Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients’ medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was...


Assuntos
Humanos , Feminino , Criança , Éxons , Estatura/genética , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Síndrome de Turner/diagnóstico , Alelos , Marcadores Genéticos , Heterozigoto , Homozigoto , Mosaicismo , Sensibilidade e Especificidade , Estatística como Assunto , Fatores de Tempo
9.
Rev. chil. tecnol. méd ; 27(1): 1339-1346, jul. 2007. ilus, graf
Artigo em Espanhol | LILACS | ID: lil-474858

RESUMO

El síndrome Xq frágil (SXF) es una causa frecuente de retraso mental (RM); se estima que uno de cada 4.000 varones y una década 6.000 mujeres lo presentan. Clínicamente los individuos afectados se caracterizan por presentar déficit intelectual y cognitivo, déficit de lenguaje, macroorquidismo, fascie alargada y orejas prominentes, entre otras dismorfias faciales. A nivel molecular es posible distinguir fundamentalmente dos tipos de alelos mutados: premutacion y mutación completa, las cuales corresponden a amplificación del trinucleótido CGG localizado en el primer exón del gen FMR1; las premutaciones presentan entre 52 y 200 repetidos y las mutaciones completas sobre 200 CGG, con hipermetilación de la región promotora del gen FMR1 e inhibición de la expresión de la proteína FMRP, causante del RM y dismorfias características de este síndrome. Desde que se identifico la mutación en 1991, la pesquisa de pacientes afectados se inicia por el examen clínico y luego el análisis citogenetico clásico y el test de screening basado en PCR para individuos varones y análisis molecular directo del gen FMR 1 por Southern Blot con la sonda Stb 12.3 para pacientes mujeres; los varones que presentan un PCR alterado deben ser confirmados por Southern Blot. El PCR debe ser usado como método de screening solo en varones con RM, sin historia familiar; es un sensible, rápido, de bajo costo y permite determinar el numero de repetidos CGG. Proponemos el uso conjunto de estos métodos para optimizar el estudio molecular directo del gen FMR1 y establecer un protocolo mas eficiente en la pesquisa de afectados, el estudio de familiares a riesgo y el consejo genético adecuado.


Assuntos
Masculino , Feminino , Humanos , Análise Citogenética/métodos , Proteínas de Ligação a RNA , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Southern Blotting , Deficiência de Ácido Fólico/complicações , Amplificação de Genes , Mutação , Reação em Cadeia da Polimerase , Repetições de Trinucleotídeos/genética , Deficiência Intelectual/genética
10.
Rev. invest. clín ; 59(1): 25-31, ene.-feb. 2007. tab
Artigo em Inglês | LILACS | ID: lil-632388

RESUMO

Introduction. Prostate cancer (PCa) is a worldwide health issue, because of its high incidence and mortality. Its etiology is complex and includes certain risk factors such as age, hormonal status, ethnic origin and family history of PCa. Genetic predisposition is proposed as a major risk factor and there are several controversial reports on the association of PCa and gene polymorphism such as the receptors of the androgen receptor (AR) and the vitamin D (VDR). Objective. To evaluate the CAG triplets repetitions in the first exon of the AR and polymorphisms in the restriction site Taql in the VDR in Mexicans with PCa. Material and methods. A total of 68 Mexicans with histopathological diagnosis of PCa and 48 healthy Mexican with normal prostate specific antigen and rectal exam where included. 10ml of peripheral blood were extracted to isolate DNA and the polymorphisms were evaluated with specific primers for the AR and VDR. Results. The allelic and genetic distributions of the AR and VDR polymorphisms were consistent with the Hardy-Weinberg equilibrium, and there were no statistical differences between the PCa patients and controls (p > 0.05). However, there was a statistical difference between the number of CAG repeats in younger patients with PCa compared to controls (p = 0.045) but when the young patient group was compared versus the elder group there was not stadistically difference (p = 0.085), but the results showed a tendency towards less repetitions of CAG in elder patients. Concerning the VDR, when we analyzed the patients with PCa and a bad pathological prognosis they had a less frequent genotype of TT (p = 0.03). Conclusions. Our results suggest an association between the VDR and AR gene polymorphisms, and the hystopathological score and age at diagnosis in Mexican patients with PCa, respectively. However, it is important to confirm these results in a larger scale study.


Introducción. El cáncer de próstata (PCa) es un problema de salud mundial, tanto por su elevada incidencia como mortalidad. Su etiología es compleja e incluye factores de riesgo reconocidos como la edad, estado hormonal, origen étnico y antecedentes familiares de PCa. El fondo genético es un factor de riesgo y existen reportes controversiales de la asociación de PCa y polimorfismos en los genes como son los receptores de vitamina D (VDR) y el de andrógenos (AR). Objetivo. Evaluar las repeticiones de tripletes de CAG en el primer exon del AR y polimorfismos en el sitio de restricción Taql en el VDR en mexicanos con PCa. Material y métodos. Se incluyeron 68 mexicanos con diagnóstico histopatológico de PCa y 48 mexicanos con niveles normales de antígeno prostático y tacto rectal normal. Se les extrajo 10 mL de sangre periférica para aislar DNA y mediante olígos específicos se evaluaron los polimorfismos mencionados. Resultados. La distribución alélica y genotípica de los polimorfismos en el AR y VDR fueron consistentes con el equilibrio de Hardy-Weinberg, y no mostraron diferencias significativas entre los casos y controles (p > 0.05). Sin embargo, el número de repeticiones de CAG en el AR fueron estadísticamente diferentes en pacientes jóvenes con PCa comparados con los controles (p = 0.045), cuando se comparó el grupo de pacientes de jóvenes contra aquellos mayores de 60 años no se encontró diferencia estadísticamente significativa (p - 0.085); sin embargo, se observó una tendencia de un número menor de repetidos CAG en pacientes mayores con PCa. Por otra parte, al comparar VDR en los pacientes con PCa de mal pronóstico por el patrón histológico tenían menor frecuencia de genotipos TT (p - 0.03). Conclusiones. Nuestros resultados sugieren una asociación entre los polimorfismos de los genes del VDR y AR, y el patrón histológico y la edad al diagnóstico en pacientes mexicanos con PCa, respectivamente. Sin embargo, es necesario confirmar estos resultados en un estudio con mayor número de pacientes.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/genética , Éxons/genética , Polimorfismo de Fragmento de Restrição , Neoplasias da Próstata/genética , Receptores Androgênicos/genética , Receptores de Calcitriol/genética , Repetições de Trinucleotídeos , Fatores Etários , Idade de Início , Adenocarcinoma/epidemiologia , Calcitriol/fisiologia , Desoxirribonucleases de Sítio Específico do Tipo II , Grupos Étnicos/genética , Predisposição Genética para Doença , Genótipo , México/epidemiologia , Neoplasias da Próstata/epidemiologia , Fatores de Risco
11.
Genet. mol. res. (Online) ; 6(1): 1-7, 2007. tab
Artigo em Inglês | LILACS | ID: lil-440615

RESUMO

Thirty-seven 45 X Turner syndrome patients with confirmed peripheral blood lymphocyte karyotype were initially selected to determine the origin of the retained X chromosome and to correlate it with their parents’ stature. Blood samples were available in 25 families. The parental origin of the X chromosome was determined in 24 informativefamilies through the analysis of the exon 1 - CAG repeat variation of the androgen receptor gene. In 70.8% of the cases, the retained X chromosome was maternal in origin and 29.2% was paternal. When we classified the patients according to maternal (Xm) or paternal (Xp) X chromosome, there was a positive correlation between patients’ and maternal heights only in the Xm group. There was no correlation with paternal height in either group, and a significant correlation with target height was only observed in the Xm group. In conclusion, maternal height is the best variable correlating with the height of 45 X Turner syndrome patients who retain the maternal X chromosome, suggesting a strong influence of genes located on the maternal X chromosome on stature.


Assuntos
Humanos , Masculino , Feminino , Estatura/genética , Cromossomos Humanos X/genética , Pais , Síndrome de Turner/genética , Éxons , Fenótipo , Reação em Cadeia da Polimerase , Receptores Androgênicos/genética , Repetições de Trinucleotídeos
12.
Genet. mol. biol ; 30(1): 14-16, 2007. graf, tab
Artigo em Inglês | LILACS | ID: lil-445677

RESUMO

Myotonic dystrophy (DM) is a neuromuscular disorder caused by the expansion of the cytosine-thymine-guanine (CTG) repeat of the myotonic dystrophy protein kinase gene (DMPK). This repeat is highly polymorphic in healthy individuals [(CTG)5-37], and it has been proposed that expanded CTG alleles originated from larger sized normal alleles [(CTG)19-37]. According to this hypothesis, a positive correlation should be expected between the frequency of these large-sized normal alleles and the prevalence of the disorder in a population. We determined the distribution of CTG alleles of the DMPK gene in 156 healthy Brazilians from Rio de Janeiro city. Our analyses of 312 chromosomes detected 20 different alleles ranging in size from 5 to 27 CTG repeats, with 24 alleles having more than 18 repeats (7.69 percent). This frequency of (CTG)3(19) alleles observed in our population suggests that the prevalence of DM in Rio de Janeiro should not be different from the prevalence in European populations.


Assuntos
Humanos , Mutação , Distrofia Miotônica , Repetições de Trinucleotídeos
13.
Braz. j. med. biol. res ; 39(8): 1129-1136, Aug. 2006. tab, graf
Artigo em Inglês | LILACS | ID: lil-433172

RESUMO

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.


Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/patologia , Doença de Huntington/genética , Doença de Huntington/patologia , Repetições de Trinucleotídeos/genética , Atrofia , Estudos de Casos e Controles , Genótipo , Imagem por Ressonância Magnética
14.
Int. braz. j. urol ; 32(3): 330-335, May-June 2006. tab
Artigo em Inglês | LILACS | ID: lil-433382

RESUMO

PURPOSE: We examined the significance of the CAG repeat polymorphism in the pathogenesis of cryptorchidism. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from blood samples from 42 cryptorchid boys and from 31 non-cryptorchid control subjects. In the cryptorchid group, 7 had bilateral cryptorchidism and 6 had patent processus vaginalis in the contralateral side. To determine the number of CAG repeats, the DNA was amplified by polymerase chain reaction and sequenced. RESULTS: The mean CAG repeat length in the AR gene was 22.5 (range 16 to 28) in patients and 21.5 (range 17 to 26) in controls (non-significant). Patients with bilateral cryptorchidism had a mean length of 24.3 (range 21 to 26) and patients with unilateral cryptorchidism and patent processus vaginalis in the contra lateral side had a mean of 25.2 (range 21 to 28), which was statistically different from controls (p = 0.015 and p = 0.005 respectively). CONCLUSION: CAG repeat length of the AR gene does not seem to play a major role in patients with unilateral cryptorchidism. However, in patients with bilateral undescended testis, a less functional androgen receptor through a longer polyglutamine chain may have a role in its pathogenesis. In the same way, patients with unilateral cryptorchidism a contralateral patent processus vaginalis have longer CAG repeats that might be responsible for a slower testicular descent and incomplete closure of the processus vaginalis.


Assuntos
Adolescente , Idoso , Criança , Pré-Escolar , Humanos , Masculino , Criptorquidismo/genética , Polimorfismo Genético/genética , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Estudos de Casos e Controles , Genótipo , Reação em Cadeia da Polimerase , Estudos Prospectivos
15.
Arq. neuropsiquiatr ; 64(1): 5-9, mar. 2006. ilus, tab
Artigo em Inglês | LILACS | ID: lil-425262

RESUMO

OBJETIVO: Descrever o quadro clínico de um grupo de pacientes com forma juvenil da doença de Huntington.MÉTODO: Os pacientes foram entrevistados seguindo um questionário clínico estruturado; genotipados para a repetição do trinucleotídeo citosina-adenina-guanina (CAG) no gene da doença de Huntington; e realizaram exame de RM de alta resolução. RESULTADOS: Identificamos 4 pacientes com doença de Huntington de início juvenil dentre 50 pacientes com doença de Huntington seguidos prospectivamente em nosso ambulatório de neurogenética. A idade de início variou entre 3 e 13 anos (2 meninos e 2 meninas). Três pacientes tiveram herança paterna da doença. O tamanho do alelo expandido da doença de Huntington variou entre 41 a 69 repetições de trinucleotídeos. As principais manifestações clínicas no início da doença foram rigidez, bradicinesia, distonia, disartria, crises epilépticas e ataxia. A RM mostrou acentuada atrofia dos núcleos caudado e putamem (p=0.001) e redução do volume cerebral e cerebelar (p=0.01). CONCLUSÃO: 8% dos pacientes com doença de Huntington acompanhados em nosso ambulatório apresentaram início juvenil da doença. Estes pacientes não apresentaram a manifestação típica de coréia observada em adultos. Houve predomínio de rigidez, bradicinesia, crises epilépticas e ataxia, o que tem relação com a atrofia cortical e cerebelar precoce na RM.


Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Encéfalo/patologia , Doença de Huntington/diagnóstico , Repetições de Trinucleotídeos/genética , Idade de Início , Análise de Variância , Atrofia , Estudos de Casos e Controles , Genótipo , Doença de Huntington/genética , Doença de Huntington/patologia , Imagem por Ressonância Magnética , Fenótipo , Estatísticas não Paramétricas , Expansão das Repetições de Trinucleotídeos/genética
16.
J. bras. med ; 88(3): 47-51, mar. 2005.
Artigo em Português | LILACS | ID: lil-661645

RESUMO

A doença de Huntington (DH) é um distúrbio hereditário autossômico dominante, que está relacionado à expansão das repetições de CAG (citosina-adenina-guanina) no braço curto do cromossomo 4, o que leva à formação de uma proteína mutante associada, principalmente, à destruição neuronal do estriado. Manifesta-se por transtornos motores, cognitivos e neuropsicológicos, evoluindo progressivamente para estado demencial grave. A patogênese da doença ainda apresenta pontos obscuros. No entanto, recentes investigações têm possibilitado maior entendimento de sua origem e evolução, assim como de outras doenças neurodegenerativas


Huntington's disease is a hereditary autosomal dominant disorder which occurs due to the expansion of the repetitions CAG on the short arm of chromosome 4, which leads to the formation of a mutant protein itself associated principally to the destruction of neuronal of the striated tissue. It manifests through motor, cognitive and neuropsychological disorders where it evolves progressively to a serious demential state. The pathogenesis of this disease still presents obscure points although recent investigations made it possible to understand it better in its origin and evolution, the same as with other neurodegenerative diseases


Assuntos
Humanos , Masculino , Feminino , /genética , Doença de Huntington/etiologia , Doença de Huntington/genética , Doença de Huntington/patologia , Proteínas Mutantes/genética , Sequências Repetitivas de Ácido Nucleico , Doenças Neurodegenerativas/etiologia , Degeneração Neural , Proteínas do Tecido Nervoso , Neurônios/patologia , Repetições de Trinucleotídeos/genética
17.
Genet. mol. biol ; 25(1): 01-06, 2002. tab, graf
Artigo em Inglês | LILACS | ID: lil-324978

RESUMO

Fragile X syndrome is the most common inherited form of mental retardation. We investigated the prevalence of the Fragile X syndrome in the population with mental retardation of unknown etiology in Andalusia, South Spain. We analyzed 322 unrelated patients (280 males and 42 females), and found a fragile X syndrome frequency of 6.5 percent. Among the non-fragile X chromosomes, the 29 CGG repeat was the most common allele. At the linked microsatellite DXS548 locus, we found a new allele which we called "allele 10" (17 CA). Similar to other south European populations, allele 2 (25 CA) at the DXS548 locus and the fragile X allele were in linkage disequilibrium supporting the idea of a common founder chromosome predisposing to the CGG expansion


Assuntos
Humanos , Masculino , Feminino , Deficiência Intelectual , Síndrome do Cromossomo X Frágil/genética , Repetições de Trinucleotídeos , Efeito Fundador , Síndrome do Cromossomo X Frágil/etiologia , Espanha
18.
Arq. neuropsiquiatr ; 59(2A): 186-191, June 2001. tab
Artigo em Inglês | LILACS | ID: lil-288619

RESUMO

In myotonic dystrophy (MD), disease severity has been correlated with expansion of CTG repeats in chromosome 19. The aims of this study were to evaluate efficacy of electromyography in the diagnosis of MD, access the frequency and the characteristics of peripheral involvement in the disease and to verify whether the CTG repeats correlated with the electrophysiological abnormalities. Twenty-five patients and six relatives at risk of carrying the MD gene were examined. Electrical myotonia (EM) was scored. Sensory and motor conduction velocity (CV) were studied in five nerves. Leukocyte DNA analysis was done in 26 subjects. Myopathy and myotonia were found in 27 cases. EM was most frequent in muscles of hand and in tibialis anterior. No significant correlation was found between EM scores and length of CTG expansions. EM scores correlated significantly with the degree of clinical myopathy, expressed by a muscular disability scale. Peripheral neuropathy was found in eight subjects and was not restricted to those who were diabetics


Assuntos
Humanos , Criança , Adulto , Adolescente , Distrofia Miotônica/diagnóstico , Repetições de Trinucleotídeos , Eletromiografia , Distrofia Miotônica/genética , Distrofia Miotônica/fisiopatologia , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas
20.
Rev. bras. genét ; 20(4): 717-24, Dez. 1997. graf
Artigo em Inglês | LILACS | ID: lil-218998

RESUMO

A doença de Machado-Joseph (MJD) é uma forma de ataxia espinocerebelar (AEC) de herança autossômica dominante, que foi descrita inicialmente em pacientes norte-americanos provenientes das ilhas portuguesas dos Açores. Clinicamente essa doença é caracterizada por uma ataxia cerebelar progressiva, de início tardio e com algumas características associadas tais como: oftalmoplegia, sinais piramidais e extrapiramidais e amiotrofias. A mutaçäo responsável é uma expansäo de trinucleotídeos CAG localizada na regiäo codificadora do gene MJD1. Como parte de um estudo colaborativo sobre AEC no Brasil, nós identificamos 25 famílias, näo aparentadas, segregando a mutaçäo MJD. Nesse artigo nós relatamos as características moleculares do trinucleotídeo CAG presente no gene MJD1 em 62 indivíduos dessas famílias com MJD e em 63 indivíduos que näo apresentam a mutaçäo MJD (126 cromossomos normais) e que foram considerados como controles. Nós observamos uma grande diferença entre os tamanhos dos alelos CAG normais e expandidos. Os alelos normais variaram entre 12 e 33 CAGs (média de 23 CAGs), enquanto que os alelos expandidos tiveram de 66 a 78 CAGs (média de 71.5 CAGs). Näo encontramos nenhuma diferença entre o tamanho dos alelos expandidos em pacientes masculinos e femininos ou entre alelos transmitidos via paterna ou materna. Uma correlaçäo negativa significante foi observada entre a idade de início da doença e o tamanho do segmento de CAG expandido (r=-0,6, P=0,00006); no entanto o tamanho do segmento de CAG expandido foi responsável por somente 40 por cento da variabilidade na idade de início da doença (r2=0.4). Nós observamos também instabilidade do segmento expandido de CAG durante a transmissäo de pais para filhos. Expansöes e contraçöes foram observadas; contudo, houve uma tendência geral para expansäo, com um aumento médio de +2,4 CAGs. Essa tendência para expansäo, pareceu ser maior nas transmissöes paternas (aumento médio de +3,5 CAGs) que nas maternas (aumento médio de +1,3 CAGs). Antecipaçäo foi observada em todas as transmissöes nas quais as idades de início para pais e filhos eram conhecidas, porém, nem todas as antecipaçöes foram acompanhadas de aumento no tamanho do segmento de CAG expandido. Em conclusäo, os nossos resultados mostram que o diagnóstico molecular da mutaçäo responsável pela MJD pode ser estabelecido em todos os indivíduos que apresentam a doença, bem como excluído naqueles portadores de outras formas de AEC.


Assuntos
Humanos , Masculino , Feminino , Adulto , Doença de Machado-Joseph , Brasil , Degenerações Espinocerebelares , Mutação/genética , Repetições de Trinucleotídeos
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