A genome-wide DNA methylation signature for SETD1B-related syndrome

Clin Epigenetics. 2019 Nov 4;11(1):156. doi: 10.1186/s13148-019-0749-3.


SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anxiety / genetics*
  • Autism Spectrum Disorder / genetics*
  • Child
  • Child, Preschool
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Epilepsy / genetics*
  • F-Box Proteins / genetics
  • Female
  • Genetic Markers
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Infant, Newborn
  • Intellectual Disability / genetics*
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Loss of Function Mutation*
  • Male


  • F-Box Proteins
  • Genetic Markers
  • Jumonji Domain-Containing Histone Demethylases
  • KDM2A protein, human
  • Histone-Lysine N-Methyltransferase
  • SETD1B protein, human