Navegando por Autor "Jardim, Laura Bannach"
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Artigo ATXN3, ATXN7, CACNA1A, and RAI1 genes and mitochondrial polymorphism a10398g did not modify age at onset in spinocerebellar ataxia type 2 patients from South America(Springer, 2015-04-14) Godeiro Junior, Clécio de Oliveira; Pereira, Fernanda S.; Monte, Thais L.; Locks-Coelho, Lucas D.; Silva, Amanda S. P.; Barsottini, Orlando; Pedroso, José L.; Cornejo-Olivas, Mario; Mazzetti, Pilar; Vargas, Fernando R.; Lima, Maria Angélica F. D.; Linden Junior, Hélio van der; Toralles, Maria Betânia Pereira; Medeiros, Paula F. V.; Ribeiro, Erlane; Braga-Neto, Pedro; Salarini, Diego; Castilhos, Raphael M.; Pereira, Maria Luiza Saraiva; Jardim, Laura Bannach; 0000-0002-4312-1633The spinocerebellar ataxia type 2 (SCA2) is a rare autosomal dominant neurodegenerative disease caused by expansions of a CAG repeat tract at ATXN2 gene. These repeats range from 22 to 31 CAG in normal alleles and from 32–34 to 64 and more, in expanded alleles. ATXN2 expansion accounts for around 50 % of the variability in age at onset (AO) of symptoms . Former studies reported that other genes may be responsible for small effects in SCA2 AO. The CAG repeats’ length (CAGn) at RAI1 gene would explain 4 % of the remaining variance in AO in 46 SCA2 patients with no clear-cut geographical origin. Two publications studied candidate genes among patients with highly discordant AO, from an original sample of 394 patients from Holguin, Cuba Their data pointed to the CAGn at CACNA1A gene [3] and to a polymorphism of the mitochondrial complex I A10398G (rs2853826) as modifiers of SCA2 AO. We have previously found that longer CAGn at ATXN3 gene were associated with earlier ages at onset in a former sample of 49 SCA2 patients from Brazil. SCA2 AO was associated with the CAGn at ATXN7 gene in a European cohort of 289 SCA2 patients but this association was not confirmed in a second cohort [6]. Since replications in additional, independent samples of patients are required to validate a genetic association, we aimed to investigate these same loci in a South American cohort of SCA2 in order to add evidences on their role as modifiers of AO in this disease.Artigo Minimal prevalence of Huntington’s disease in the South of Brazil and instability of the expanded CAG tract during intergenerational transmissions(SciELO, 2019) Godeiro Junior, Clécio de Oliveira; Castilhos, Raphael Machado de; Santos, José Augusto dos; Augustin, Marina Coutinho Augustin; Pedroso, José Luiz; Barsottini, Orlando; Saba, Roberta; Ferraz, Henrique Ballalai; Vargas, Fernando Regla; Salarini, Diego Zanotti; Furtado, Gabriel Vasata; Polese-Bonatto, Marcia; Rodrigues, Luiza Paulsen; Sena, Lucas Schenatto; Saraiva-Pereira, Maria Luiza; Jardim, Laura Bannach; 0000-0002-4312-1633Huntington’s disease (HD) is due to dominant expansions of the CAG repeat of the HTT gene. Meiotic instability of the (CAG)n might impact the disorder frequency. We report on HD minimal prevalence in Rio Grande do Sul (RS) state, Brazil, and on intergenerational instability of the (CAG)n in HD families. Symptomatic and at-risk subjects from 179 HD families were ascertained between 2013 and 2016. Clinical, molecular and family history data were obtained. Expanded (CAG)n length differences between parent and child (delta-expanded-(CAG)n) were calculated. Effect of parental age on the (CAG)n instability upon transmission was inferred by correlating delta-expanded-(CAG)n between siblings to their age differences. HD minimal prevalence in RS state was estimated as 1.85:100,000 inhabitants. Alleles with (CAG)27-35 were found on 21/384 non-disease associated chromosomes (5.5%); among 253 expanded alleles, four (1.6%) were within reduced penetrance range with (CAG)36-39. In 32 direct transmissions, mean instability was larger among paternal than maternal transmissions. In direct transmissions and in 51 sibling pairs, parental age at the time of child birth were not correlated with delta-expanded-(CAG)n. Briefly, HD prevalence in RS state was lower than those reported for European populations. Expanded (CAG)n transmissions were unstable and not associated to parental age.Artigo Selective forces related to spinocerebellar ataxia type 2(Springer, 2018-09-15) Godeiro Junior, Clécio de Oliveira; Sena, Lucas Schenatto; Castilhos, Raphael Machado; Mattos, Eduardo Preusser; Furtado, Gabriel Vasata; Pedroso, José Luiz; Barsottini, Orlando; Amorim, Maria Marla Paiva de; Pereira, Maria Luiza Saraiva; Jardim, Laura Bannach; 0000-0002-4312-1633Spinocerebellar ataxia type 2 (SCA2) is caused by an unstable expanded CAG repeat tract (CAGexp) at ATXN2. Although prone to selective forces such as anticipation, SCA2 frequency seems to be stable in populations. Our aim was to estimate reproductive success, segregation patterns, and role of anticipation in SCA2. Adult subjects from families with molecular diagnosis provided data about all his/her relatives. Affected and unaffected sibs older than 65.7 years of age were used to estimate reproductive success and segregation patterns. Twenty-one SCA2 families were studied, including 1017 individuals (164 affected) who were born from 1840 to 2012. The median number of children of the non-carriers and carriers, among 99 subjects included in the reproductive success analysis, were 2 and 3 (p < 0.025), respectively. Therefore, the reproductive success of carriers was 1.5. There were 137 non-carriers (59.6%) and 93 carriers (40.4%) (p = 0.04), among subjects included in the segregation analysis. Age at onset across generations pointed to anticipation as a frequent phenomenon. We raised evidence in favor of increased reproductive success related to the carrier state at ATXN2, and segregation distortion favoring normal alleles. Since majority of normal alleles analyzed carried 22 repeats, we propose that this distortion segregation can be related to the high frequency of this allele in human chromosomes.