Screening for germline BRCA1, BRCA2, TP53 and CHEK2 mutations in families at-risk for hereditary breast cancer identified in a population-based study from Southern Brazil

Abstract In Brazil, breast cancer is a public health care problem due to its high incidence and mortality rates. In this study, we investigated the prevalence of hereditary breast cancer syndromes (HBCS) in a population-based cohort in Brazils southernmost capital, Porto Alegre. All participants answered a questionnaire about family history (FH) of breast, ovarian and colorectal cancer and those with a positive FH were invited for genetic cancer risk assessment (GCRA). If pedigree analysis was suggestive of HBCS, genetic testing of the BRCA1, BRCA2, TP53, and CHEK2 genes was offered. Of 902 women submitted to GCRA, 214 had pedigrees suggestive of HBCS. Fifty of them underwent genetic testing: 18 and 40 for BRCA1/BRCA2 and TP53 mutation screening, respectively, and 7 for CHEK2 1100delC testing. A deleterious BRCA2 mutation was identified in one of the HBOC probands and the CHEK2 1100delC mutation occurred in one of the HBCC families. No deleterious germline alterations were identified in BRCA1 or TP53. Although strict inclusion criteria and a comprehensive testing approach were used, the suspected genetic risk in these families remains unexplained. Further studies in a larger cohort are necessary to better understand the genetic component of hereditary breast cancer in Southern Brazil

Consolidação de um Projeto Piloto de Identificação de Fatores de Risco para Câncer de Mama Hereditário de Base Populacional Vinculado ao Programa de Saúde da Família

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Consolidação de um Projeto Piloto de Identificação de Fatores de Risco para Câncer de Mama Hereditário de Base Populacional Vinculado ao Programa de Saúde da Família

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Maple syrup urine disease in Brazil: a panorama of the last two decades

Objective: To characterize a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011. Methods: In this retrospective study, patients were identified through a national reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. Data were collected by means of a chart review. Results: Eighty‐three patients from 75 families were enrolled in the study (median age, 3 years; interquartile range [IQR], 0.57‐7). Median age at onset of symptoms was 10 days (IQR 5‐30), whereas median age at diagnosis was 60 days (IQR 29‐240, p = 0.001). Only three (3.6%) patients were diagnosed before the onset of clinical manifestations. A comparison between patients with (n = 12) and without (n = 71) an early diagnosis shows that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. Overall, 98.8% of patients have some psychomotor or neurodevelopmental delay. Conclusion: In Brazil, patients with MSUD are usually diagnosed late and exhibit neurological involvement and poor survival even with early diagnosis. We suggest that specific public policies for diagnosis and treatment of MSUD should be developed and implemented in the country