The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

A family segregating lethal neonatal coenzyme Q(10) deficiency caused by mutations in COQ9

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Illustrative Prospective of Solar Energy in Urban Planning: Collection of International Case Studies

This reports presents a collection of 34 case studies on solar energy in urban planning, addressing how the planning process has been developed, how the stakeholders have been involved, which instruments have been applied, which energy technology and environmental impact have been addressed and what the role was of the researchers during the entire process. The case studies from 10 countries include examples of new urban areas, existing urban areas and landscapes. Document Number: Task 51/Report C

Tamanho ao nascer e problemas de saúde mental aos 11 anos em uma coorte brasileira de nascimentos

O objetivo foi avaliar a associação entre tamanho ao nascer e problemas de saúde mental aos 11 anos na Coorte de Nascimentos de Pelotas, Rio Grande do Sul, Brasil, de 1993. Foram pesados e medidos ao nascer 4.358 recém-nascidos. Avaliou-se problemas de saúde mental com o questionário de capacidades e dificuldades (Strengths and Difficulties Questionnaire - SDQ). A prevalência de problemas de saúde mental foi de 32% (IC95%: 31-33). Na análise ajustada, os 291 (6,7%) recém-nascidos com escorez de peso/idade e os 268 (6,2%) com índice de massa corporal (IMC)/idade < -2 DP tiveram, respectivamente, 27% (IC95%: 7-49) e 29% (IC95%: 10-51) maior risco de apresentar problemas de saúde mental aos 11 anos quando comparados com aqueles com escore normal. Os 102 (2,43%) recém-nascidos com escorez de IMC e os 279 (6,4%) com perímetro cefálico/idade > +2 DP tiveram, respectivamente, 34% (IC95%: 6-71) e 19% (IC95%: 1-40) maior risco de apresentar esses problemas se comparados com aqueles com escore normal. Os resultados sugerem que fatores ocorridos na gestação e refletidos nas medidas de tamanho ao nascer podem ocasionar problemas de saúde mental em etapas tardias