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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 9
[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
Total Affiliations: 9
Document type: Journal article
Web of Science Citations: 1

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)

FAPESP's process: 15/22758-8 - Characterization of methylation profile during tumor progression of Wilms tumors
Grantee:João Victor da Silva Guerra
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/06281-7 - Characterization of the epigenetic regulation in human solid paediatric tumours
Grantee:Mariana Camargo Maschietto
Support type: Scholarships in Brazil - Young Researchers