97 research outputs found
The CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation
Huntington disease (HD) is caused by an
expansion of a CAG repeat. This repeat is a dynamic
mutation that tends to undergo intergenerational instability.
We report the analysis of the CAG repeat in a large
population sample (2,000 chromosomes) covering all regions
of Portugal, and a haplotype study of (CAG)n and
(CCG)n repeats in 140 HD Portuguese families. Intermediate
class 2 alleles represented 3.0% of the population;
and two expanded alleles (36 and 40 repeats, 0.11%) were
found. There was no evidence for geographical clustering
of the intermediate or expanded alleles. The Portuguese
families showed three different HD founder haplotypes
associated with 7-, 9- or 10-CCG repeats, suggesting the
possibility of different origins for theHDmutation among
this population. The haplotype carrying the 7-CCG repeat
was the most frequent, both in normal and in expanded
alleles. In general, we propose that three mechanisms,
occurring at different times,may lead to the evolution from
normal CAGs to full expansion: first, a mutation bias towards
larger alleles; then, a stepwise process that could
explain the CAGdistributions observed in themore recent
haplotypes; and, finally, a pool of intermediate (class 2)
alleles more prone to give rise to expanded HD alleles.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/9759/
2003.Instituto de Genética Médica Jacinto Magalhães
Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis
A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age
Molecular diagnosis of Huntington disease in Portugal : implications for genetic counselling and clinical practice
Huntington disease (HD) is a eurodegenerative, autosomal dominant disorder of late-onset, caused by
the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and four for prenatal testing (four were done for family studies). Most referring physicians were neurologists (90.6%); 82.8% of all clinical diagnosis were confirmed, while 83.1% of those sent for exclusion were in fact excluded. In presymptomatic testing,
an excess of female subjects (59.4%) was again verified; 37.5% of the consultands were found to be carriers. None of the foetuses, in four prenatal tests, were mutation carriers. One juvenile case was
inherited from her mother. Our patient population is very similar to others described so far, namely in terms of mean age at onset and (CAG)n distribution, except perhaps for a higher frequency of large normal (class 2) alleles (3.7%). We also identify cases posing particular problems for genetic counselling, such as, ‘homozygosity’ that can pose a serious ethical dilemma, carriers of large normal alleles, and ‘homoallelism’ for a normal gene, which will demand further procedures and may delay results in presymptomatic and prenatal testing
A evolução do conhecimento sobre as hepatites virais na região amazônica: da epidemiologia e etiologia à prevenção
Desde os anos cinqüenta uma doença similar a febre amarela, porém considerada como nova doença, ocorre em áreas dos vales dos Rios Juruá, Purus e Madeira. Temida pelos residentes locais pela alta letalidade, sendo clinicamente uma hepato-encefalopatia de evolução fulminante (média de 5 a 6 dias). Dos que apresentam manifestações neurológicas 90% evoluem a óbito. A doença é popularmente conhecida como febre negra de Lábrea e pelos patologistas como hepatite de Lábrea pela histopatologia hepática mostrar o aspecto vacuolar dos hepatócitos, daí considerarem-na uma nova doença. Incide principalmente em crianças e adolescentes do sexo masculino. O achado do HBsAg e de marcadores de vírus da hepatite D no soro e fígado dos pacientes, levaram os pesquisadores a considerarem a febre negra de Lábrea como uma superinfecção ou coinfecção do HDV. Na falta de vacina específica contra o HDV, a vacinação contra hepatite B aplicada após o nascimento é a prevenção recomendada
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