A 3 bp deletion of codon 508 (phenylalanine) of the cystic fibrosis (CF) gene constitutes the mutation of most CF chromosomes. The frequency of this mutation (referred to as delta F508), varies considerably between populations, ranging from 26% of the CF mutations in Turkey to 88% in Denmark. To determine the frequency of the delta F508 mutation in Brazilian Caucasoid CF patients, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards, followed by ethidium bromide staining of gels. Although the overall frequency of the delta F508 mutation was 47% of 380 CF chromosomes from Brazilian Caucasoids born in five different states, significant interstate differences were observed, ranging from a delta F508 frequency of 27% to 53%. While our method could be used to screen patients and their relatives for carrier testing and prenatal diagnosis, the efficacy of screening only for the delta F508 mutation would be low, and would vary from state to state. Screening for a panel of local mutations will be needed to increase the mutation detection rate and optimize genetic counseling.

RESUMO Objetivo Investigar a qualidade de vida familiar (QVF) entre famílias brasileiras que têm filhos com deficiência intelectual (DI) moderada. Métodos Estudo transversal, realizado com 50 famílias com filhos com DI moderada de São Carlos, São Paulo, Brasil. Os dados foram coletados por meio de formulários, com informações sociodemográficas, os índices de funcionalidade de Barthel e de Lawton & Brody e a Escala de Qualidade de Vida Familiar do Beach Center. Resultados Os domínios mais fortemente correlacionados com a QVF total foram “interação familiar” (r = 0,870; p < 0,001) e “cuidado dos pais com os filhos” (r = 0,845; p < 0,001). Não houve diferenças na distribuição da QVF em relação às variáveis sociodemográficas investigadas. Observou-se correlação moderada (r = 0,326) e significativa (p = 0,021) entre o índice de funcionalidade de Lawton & Brody e a QVF. O modelo de regressão linear ajustado explicou 10,6% da variabilidade encontrada na QVF (p = 0,021) e mostrou que o aumento de uma unidade no valor do índice de Lawton & Brody representou aumento de 0,092 na QVF. Conclusão A QVF das famílias investigadas encontra-se aquém de outras amostras internacionais. Ações clínicas que fortaleçam o diálogo e a coesão familiar e a construção de um plano terapêutico individualizado podem ser meios efetivos de ajuda a essas famílias.

Recently, an article on the prevalence of autism spectrum disorder (ASD) in Down Syndrome (DS) 1 has been published. The aforementioned work discusses the sensitivity and specificity of 2 instruments used for the screening of ASD in a population with mental retardation, particularly DS, and suggests that the instruments currently available for diagnosis of ASD have low specificity. Our research group (Lowenthal et al) had already evaluated a sample of 228 individuals with DS in the city of Curitiba, capital of the state of Paraná, in the south of Brazil and had found increased prevalence of ASD (14.5% in our study vs 18.2% in the study by DiGuiseppi et al) being 4.9% for autism (6.4% in the study by DiGiuseppi et al).In a more recent study, DiGiuseppi et al 1 discuss the implications of the higher sensitivity of the instruments at the expense of specificity. In this sense, we have decided to reexamine the Brazilian DS cohort, 2 looking into new possibilities with respect to the specificity of one of the instruments used, the Autism Screening Questionnaire (ASQ). The preliminary validation study of the Brazilian version of the ASQ had suggested the same cutoff points as those of the original study (without ASD [Ͻ15], with ASD [Ն15 and Ͻ21], and autism [Ն22]) 3 in a cohort of 120 participants (40 ASD, 40 DS, and 40 other psychiatric disorders). 4 First, we decided to verify the sensitivity and specificity of the cutoff point Ն15 applied to our sample. A sensitivity of 88.2% and a specificity of 53.3%, with good ability to recognize ASD cases (p ϭ 0.021), were found. To search for new cutoff points for this DS/ASD population, a classification analysis by decision tree test confirmed by receiver operator characteristic curve was accomplished, which furnished a cutoff point of 18, in which sensitivity and specificity were 76.5% and 93.3%, respectively (area below the curve ϭ 0.884). Despite the decreased sensitivity, this increase in the cutoff point allowed for higher specificity, which should provide this screening instrument with improved psychometric property. Many of the symptoms that are part of the ASD screening instruments are very common in subjects with intellectual disability, which can cause individuals with DS to present with isolated symptoms, thereby justifying the elevation of the ASQ cutoff point during screening of ASD cases. For this reason, an instrument with higher specificity should avoid problems with identification of false positives, which have financial implications and result in burden for the families, 1 especially in investigations involving large cohorts of patients.The increased frequency of ASD in DS suggests that large epidemiologic studies should be performed on this population. As in the case of studies on other associations between low-frequency pathologies, such large studies on ASD/DS would probably facilitate the search for genes and polymorphisms associated with ASD, thus aiding better understanding of the development of the social brain in individuals with DS. Finally, screenin...

Background: Intellectual disability (ID) and autism spectrum disorder (ASD) are often concomitant childhood developmental disorders. These disorders can alter family quality of life (FQoL). Objective: To investigate FQoL among families who have children with mild ID, associated with mild ASD. Methods: Cross-sectional descriptive study with 69 families who have children with mild ID and ASD, ranging from six to 16 years old, and who were provided with disability-related services in Brazil. Data were collected using a family sociodemographic questionnaire, an ID and ASD personal profile form, the Barthel index for activities of daily living and the Beach Center FQoL scale. Results: People with ID and ASD had an average score of 88.2±11.5 in the Barthel index, thus indicating moderate dependency in basic activities of daily living. The average total FQoL score (3.56±0.34) was lower than the scores for the “family interaction” (3.91±0.42; p<0.001), “parenting” (3.79±0.35; p<0.001) and “disability-related support” (3.98±0.16; p<0.001) domains; and higher than the scores for the “physical/material well-being” (3.19±0.64; p<0.001) and “emotional wellbeing” (2.75±0.62; p<0.001) domains. Parents’ marital condition, monthly family income, family religious practice and effective communication skills among the people with ID and ASD were predictors for FQoL (R2=0.407; p<0.001). Conclusions: FQoL was sustained through factors such as family interaction and parents’ care for their children. Improving families’ emotional wellbeing and physical and material conditions is likely to positively affect the FQoL of these families.

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SUMMARY -The authors describe a family with three members affected by glioblastoma. The proband patient, a 7 year-old girl, developed a rare complication, a pulmonary metastasis. Chromosomal analysis of her peripheral blood lymphocytes showed a normal karyotype (46, XX), without structural abnormalities. Cytogenetic study of the tumor cells disclosed several abnormalities: 46, XX, 7q -/ 46, XX, -2, 4p-, 7p-, +15/ 46, XX. Some aspects about genetics of glial neoplasms are discussed.KEY WORDS : glioblastoma, chromosomes, cytogenetics, oncogenesis. Glioblastoma familiarRESUMO -Os autores descrevem uma família com três membros portadores de glioblastoma. A paciente probanda, uma menina de 7 anos, apresentou metástase pulmonar. A análise cromossômica dos linfócitos periféricos revelou um cariótipo normal (46, XX). Estudo citogenético das células tumorais mostrou várias anormalidades: 46, XX, 7q-/ 46, XX, -2,4p-, 7p-, +15 / 46, XX. Alguns aspectos sobre oncogênese e citogenética das neoplasias gliais são discutidos.

Objetivos: Examinar estudos sobre diagnóstico etiológico nas situações de deficiência intelectual ou atraso global do desenvolvimento, racionalizando o processo de investigação causal em um fluxograma aplicável na prática clínica. Método: Revisão não sistemática da literatura nas bases de dados PubMed e SciELO, sem restrições de tempo ou idioma, com seleção de artigos relevantes, análise crítica e síntese dos resultados. Resultados: Causas ambientais de deficiência devem ser consideradas na história clínica, identificando-se fatores de risco pré, peri e pós-natais. A história familiar e os exames físico, dismorfológico e neurológico podem sugerir a etiologia e orientar a investigação. Para investigar causas genéticas, a análise cromossômica por microarray é indicada como teste de primeira linha, associada à pesquisa de erros inatos do metabolismo e à testagem para síndrome do X-frágil. Exames de neuroimagem são importantes em pacientes selecionados, assim como a investigação de outros genes localizados no cromossomo X. Há uma discussão emergente sobre o papel do sequenciamento completo do exoma nessa investigação. Conclusões: A frequência de definição etiológica tem aumentado com a incorporação de novas tecnologias genéticas na investigação da deficiência intelectual. Afora a investigação etiológica, a abordagem clínica deve considerar diferentes demandas e permitir a construção de um plano terapêutico individualizado.