RESUMEN
BACKGROUND: Ten neurodegenerative disorders characterized by spinocerebellar ataxia (SCA) are known to be caused by trinucleotide repeat (TNR) expansions. However, in some instances the molecular diagnosis is considered indeterminate because of the overlap between normal and affected allele ranges. In addition, the mechanism that generates expanded alleles is not completely understood. OBJECTIVE: To examine the clinical and molecular characteristics of a large group of Portuguese and Brazilian families with ataxia to improve knowledge of the molecular diagnosis of SCA. PATIENTS AND METHODS: We have (1) assessed repeat sizes at all known TNR loci implicated in SCA; (2) determined frequency distributions of normal alleles and expansions; and (3) looked at genotype-phenotype correlations in 202 unrelated Portuguese and Brazilian patients with SCA. Molecular analysis of TNR expansions was performed using polymerase chain reaction amplification. RESULTS: Patients from 110 unrelated families with SCA showed TNR expansions at 1 of the loci studied. Dominantly transmitted cases had (CAG)(n) expansions at the Machado-Joseph disease gene (MJD1) (63%), at SCA2 (3%), the gene for dentatorubropallidoluysian atrophy (DRPLA) (2%), SCA6 (1%), or SCA7 (1%) loci, or (CTG)(n) expansions at the SCA8 (2%) gene, whereas (GAA)(n) expansions in the Freidreich ataxia gene (FRDA) were found in 64% of families with recessive ataxia. Isolated patients also had TNR expansions at the MJD1 (6%), SCA8 (6%), or FRDA (8%) genes; in addition, an expanded allele at the TATA-binding protein gene (TBP), with 43 CAGs, was present in a patient with ataxia and mental deterioration. Associations between frequencies of SCA2 and SCA6 and a frequency of large normal alleles were found in Portuguese and Brazilian individuals, respectively. Interestingly, no association between the frequencies of DRPLA and large normal alleles was found in the Portuguese group. CONCLUSIONS: Our results show that (1) a significant number of isolated cases of ataxia are due to TNR expansions; (2) expanded DRPLA alleles in Portuguese families may have evolved from an ancestral haplotype; and (3) small (CAG)(n) expansions at the TBP gene may cause SCA17.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/genética , Expansión de Repetición de Trinucleótido , Adenina/metabolismo , Adulto , Anciano , Alelos , Brasil , Citosina/metabolismo , Femenino , Guanina/metabolismo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , Reacción en Cadena de la Polimerasa , PortugalRESUMEN
Foram estudados 2.980 casos de alcoolismo no PSM de Juiz de Fora (MG); todos os casos apresentando sinais de ingesta recente de bebida alcoolica, motivo pelo qual procuraram assistencia medica. A hipertensao arterial (HA) foi encontrada em 68 individuos (2,28%), perfazendo 56 homens e 12 mulheres; 19 brancos, 40 pretos e 9 mulatos. A maioria da populacao estudada era jovem (15-35 anos), o mais jovem hipertenso com 15 anos e o mais velho com 65 anos. A HA foi mais frequente nos individuos pretos entre 26 e 45 anos (p< 0,05). 41,17% apresentaram-se hipertensos com alcoolismo tipo agudo e 58,83% hipertensos com alcoolismo tipo cronico. Conclui-se que a HA na populacao alcoolatra estudada coincide com a maior frequencia da HA essencial que incide sobre a raca masculina jovem