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

Clin Epigenetics. 2020 Jan 7;12(1):7. doi: 10.1186/s13148-019-0804-0.


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.

Keywords: Accelerated aging; Chromatin remodeling; DNA methylation; Episignature; HIST1H1E; Intellectual disability; Rahman syndrome; Replicative senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism
  • DNA Methylation*
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / metabolism
  • Epigenesis, Genetic
  • Frameshift Mutation*
  • Histones / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / metabolism
  • Neurons / metabolism
  • Signal Transduction / genetics
  • Syndrome


  • H1-4 protein, human
  • Histones