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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

DNA methylation fingerprint of monozygotic twins and their singleton sibling with intellectual disability carrying a novel KDM5C mutation

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Autor(es):
Guerra, Joao V. S. [1, 2] ; Oliveira-Santos, Jose [3] ; Oliveira, Danyllo F. [4, 5, 3] ; Leal, Gabriela F. [6, 7] ; Oliveira, Joao Ricardo M. [4, 5] ; Costa, Silvia S. [3] ; Krepischi, V, Ana C. ; Vianna-Morgante, Angela M. [8] ; Maschietto, Mariana [1, 9]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Inst Biol, Postgrad Program Biosci & Technol Bioact Prod, Campinas, SP - Brazil
[3] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Sao Paulo, SP - Brazil
[4] Univ Fed Pernambuco, Dept Neuropsychiat, Recife, PE - Brazil
[5] Univ Fed Pernambuco, Keizo Asami Lab, Recife, PE - Brazil
[6] Univ Pernambuco, Recife, PE - Brazil
[7] Prof Fernando Figueira Integral Med Inst, Recife, PE - Brazil
[8] Krepischi, Ana C., V, Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Sao Paulo, SP - Brazil
[9] Boldrini Childrens Hosp, Rua Dr Gabriel Porto 1270, Cidade Univ, BR-13083210 Campinas, SP - Brazil
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: EUROPEAN JOURNAL OF MEDICAL GENETICS; v. 63, n. 3 MAR 2020.
Citações Web of Science: 1
Resumo

Mutations in KDM5C (lysine (K)-specific demethylase 5C) were causally associated with up to 3% of X-linked intellectual disability (ID) in males. By exome and Sanger sequencing, a novel frameshift KDM5C variant, predicted to eliminate the JmjC catalytic domain from the protein, was identified in two monozygotic twins and their older brother, which was inherited from their clinically normal mother, who had completely skewed X-inactivation. DNA methylation (DNAm) data were evaluated using the Illumina 450 K Methylation Beadchip arrays. Comparison of methylation levels between the three patients and male controls identified 399 differentially methylated CpG sites, which were enriched among those CpG sites modulated during brain development. Most of them were hypomethylated (72%), and located mainly in shores, whereas the hypermethylated CpGs were more represented in open sea regions. The DNAm changes did not differ between the monozygotic twins nor between them and their older sibling, all presenting a global hypomethylation, similar to other studies that associated DNA methylation changes to different KDM5C mutations. The 38 differentially methylated regions (DMRs) were enriched for H3K4me3 marks identified in developing brains. The remarkable similarity between the methylation changes in the monozygotic twins and their older brother is indicative that these epigenetic changes were mostly driven by the KDM5C mutation. (AU)

Processo FAPESP: 15/06281-7 - Investigação da regulação epigenética em tumores sólidos pediátricos
Beneficiário:Mariana Camargo Maschietto
Linha de fomento: Bolsas no Brasil - Apoio a Jovens Pesquisadores
Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
Beneficiário:Mayana Zatz
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 15/22758-8 - Caracterização dos padrões de metilação durante a progressão tumoral de Tumores de Wilms
Beneficiário:João Victor da Silva Guerra
Linha de fomento: Bolsas no Brasil - Iniciação Científica