Macrocephaly frequently occurs in single-gene disorders affecting the PI3K-AKT-MTOR pathway; however, epigenetic mutations, mosaicism, and copy number variations (CNVs) are emerging relevant causative factors, revealing a higher genetic heterogeneity than previously expected. The aim of this study was to investigate the role of rare CNVs in patients with macrocephaly and review genomic loci and known genes. We retrieved from the DECIPHER database de novo <500 kb CNVs reported on patients with macrocephaly; in four cases, a candidate gene for macrocephaly could be pinpointed: a known microcephaly gene –TRAPPC9, and three genes based on their functional roles – RALGAPB, RBMS3, and ZDHHC14. From the literature review, 28 pathogenic CNV genomic loci and over 300 known genes linked to macrocephaly were gathered. Among the genomic regions, 17 CNV loci (~61%) exhibited mirror phenotypes, that is, deletions and duplications having opposite effects on head size. Identifying structural variants affecting head size can be a preeminent source of information about pathways underlying brain development. In this study, we reviewed these genes and recurrent CNV loci associated with macrocephaly, as well as suggested novel potential candidate genes deserving further studies to endorse their involvement with this phenotype.
O Ensino por Investigação é uma importante ferramenta para criação de situações pedagógi-cas em que os estudantes aprendem e exercitam habilidades próprias da atividade científica. Os cetáceos são um grupo de mamíferos aquáticos cujo registro fóssil documenta a passa-gem de um ancestral terrestre para o ambiente marinho de forma gradual. O presente artigo apresenta uma proposta de sequência didática investigativa, na qual os alunos devem utilizar filogenias, análises morfológicas e seus conhecimentos sobre classificação biológica para re-solver uma questão-problema sobre a ancestralidade dos cetáceos. Além disso, relatamos a experiência de aplicação desta sequência didática em uma escola pública, em turmas do 7⁰ ano em São Paulo.
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