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

Authors
  • Guerra, João V S1
  • Oliveira-Santos, José2
  • Oliveira, Danyllo F3
  • Leal, Gabriela F4
  • Oliveira, João Ricardo M5
  • Costa, Silvia S6
  • Krepischi, Ana C V7
  • Vianna-Morgante, Angela M8
  • Maschietto, Mariana9
  • 1 Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Postgraduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, University of Campinas, Campinas, SP, Brazil. Electronic address: [email protected] , (Brazil)
  • 2 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, SP, Brazil. Electronic address: [email protected] , (Brazil)
  • 3 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, SP, Brazil; Department of Neuropsychiatry and Keizo Asami Laboratory, Federal University of Pernambuco, Recife, PE, Brazil. Electronic address: [email protected] , (Brazil)
  • 4 University of Pernambuco and Professor Fernando Figueira Integral Medicine Institute, Recife, PE, Brazil. Electronic address: [email protected] , (Brazil)
  • 5 Department of Neuropsychiatry and Keizo Asami Laboratory, Federal University of Pernambuco, Recife, PE, Brazil. Electronic address: [email protected] , (Brazil)
  • 6 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, SP, Brazil. Electronic address: [email protected] , (Brazil)
  • 7 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, SP, Brazil. Electronic address: [email protected] , (Brazil)
  • 8 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, SP, Brazil. Electronic address: [email protected] , (Brazil)
  • 9 Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil; Boldrini Children's Hospital, Campinas, SP, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Mar 01, 2020
Volume
63
Issue
3
Pages
103737–103737
Identifiers
DOI: 10.1016/j.ejmg.2019.103737
PMID: 31419599
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2019 Elsevier Masson SAS. All rights reserved.

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