Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature: Clinical Epigenetics

A. Ciolfi, E. Aref-Eshghi, S. Pizzi, L. Pedace, E. Miele, J. Kerkhof, E. Flex, S. Martinelli, F.C. Radio, C.A.L. Ruivenkamp, G.W.E. Santen, E. Bijlsma, D. Barge-Schaapveld, K. Ounap, V.M. Siu, R.F. Kooy, B. Dallapiccola, B. Sadikovic, M. Tartaglia

Research output: Contribution to journalArticlepeer-review


Background : We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. Results: Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. Conclusions: We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis. © 2020 The Author(s).
Original languageEnglish
JournalClin. Epigenetics
Issue number1
Publication statusPublished - 2020


  • Accelerated aging
  • Chromatin remodeling
  • DNA methylation
  • Episignature
  • HIST1H1E
  • Intellectual disability
  • Rahman syndrome
  • Replicative senescence
  • Article
  • behavior disorder
  • blood sampling
  • bone disease
  • carboxy terminal sequence
  • case report
  • cell function
  • child
  • clinical article
  • congenital skin disease
  • controlled study
  • cutis laxa
  • developmental delay
  • developmental disorder
  • face malformation
  • frameshift mutation
  • gene
  • gene expression profiling
  • genetic screening
  • HIST1H1E gene
  • human
  • human cell
  • hypotrichosis
  • intellectual impairment
  • male
  • mutational analysis
  • nerve cell
  • nervous system development
  • preschool child
  • priority journal
  • promoter region
  • sensitivity and specificity
  • sequence analysis
  • single nucleotide polymorphism


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