848 resultados para Developmental toxicity


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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A number of speech disorders including stuttering have been shown to have important genetic contributions, as indicated by high heritability estimates from twin and other studies. We studied the potential contribution to stuttering from variants in the FOXP2 gene, which have previously been associated with developmental verbal dyspraxia, and from variants in the CNTNAP2 gene, which have been associated with specific language impairment (SLI). DNA sequence analysis of these two genes in a group of 602 unrelated cases, all with familial persistent developmental stuttering, revealed no excess of potentially deleterious coding sequence variants in the cases compared to a matched group of 487 well characterized neurologically normal controls. This was compared to the distribution of variants in the GNPTAB, GNPTG, and NAGPA genes which have previously been associated with persistent stuttering. Using an expanded subject data set, we again found that NAGPA showed significantly different mutation frequencies in North Americans of European descent (p = 0.0091) and a significant difference existed in the mutation frequency of GNPTAB in Brazilians (p = 0.00050). No significant differences in mutation frequency in the FOXP2 and CNTNAP2 genes were observed between cases and controls. To examine the pattern of expression of these five genes in the human brain, real time quantitative reverse transcription PCR was performed on RNA purified from 27 different human brain regions. The expression patterns of FOXP2 and CNTNAP2 were generally different from those of GNPTAB, GNPTG and NAPGA in terms of relatively lower expression in the cerebellum. This study provides an improved estimate of the contribution of mutations in GNPTAB, GNPTG and NAGPA to persistent stuttering, and suggests that variants in FOXP2 and CNTNAP2 are not involved in the genesis of familial persistent stuttering. This, together with the different brain expression patterns of GNPTAB, GNPTG, and NAGPA compared to that of FOXP2 and CNTNAP2, suggests that the genetic neuropathological origins of stuttering differ from those of verbal dyspraxia and SLI. Published by Elsevier Inc.

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Evidence from opaque languages suggests that visual attention processing abilities in addition to phonological skills may act as cognitive underpinnings of developmental dyslexia. We explored the role of these two cognitive abilities on reading fluency in Brazilian Portuguese, a more transparent orthography than French or English. Sixty-six children with developmental dyslexia and normal Brazilian Portuguese children participated. They were administered three tasks of phonological skills (phoneme identification, phoneme, and syllable blending) and three visual tasks (a letter global report task and two non-verbal tasks of visual closure and visual constancy). Results show that Brazilian Portuguese children with developmental dyslexia are impaired not only in phonological processing but further in visual processing. The phonological and visual processing abilities significantly and independently contribute to reading fluency in the whole population. Last, different cognitively homogeneous subtypes can be identified in the Brazilian Portuguese population of children with developmental dyslexia. Two subsets of children with developmental dyslexia were identified as having a single cognitive disorder, phonological or visual; another group exhibited a double deficit and a few children showed no visual or phonological disorder. Thus the current findings extend previous data from more opaque orthographies as French and English, in showing the importance of investigating visual processing skills in addition to phonological skills in children with developmental dyslexia whatever their language orthography transparency.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)