The defining DNA methylation signature of Floating-Harbor Syndrome

Sci Rep. 2016 Dec 9;6:38803. doi: 10.1038/srep38803.


Floating-Harbor syndrome (FHS) is an autosomal dominant genetic condition characterized by short stature, delayed osseous maturation, expressive language impairment, and unique facial dysmorphology. We previously identified mutations in the chromatin remodeling protein SRCAP (SNF2-related CBP Activator Protein) as the cause of FHS. SRCAP has multiple roles in chromatin and transcriptional regulation; however, specific epigenetic consequences of SRCAP mutations remain to be described. Using high resolution genome-wide DNA methylation analysis, we identified a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of individuals with FHS. Both hyper and hypomethylated loci are distributed across the genome, preferentially occurring in CpG islands. Clonal bisulfite sequencing of two hypermethylated (FIGN and STPG2) and two hypomethylated (MYO1F and RASIP1) genes confirmed these findings. The identification of a unique methylation signature in FHS provides further insight into the biological function of SRCAP and provides a unique biomarker for this disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • Abnormalities, Multiple / blood
  • Abnormalities, Multiple / genetics*
  • Adenosine Triphosphatases / blood
  • Adenosine Triphosphatases / deficiency
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / physiology
  • Adolescent
  • Adult
  • Bone Diseases, Developmental / genetics*
  • Child
  • Child, Preschool
  • Chromatin Assembly and Disassembly
  • Codon, Nonsense
  • CpG Islands / genetics
  • DNA / blood
  • DNA / genetics
  • DNA Methylation*
  • Dwarfism / blood
  • Dwarfism / genetics*
  • Face / abnormalities*
  • Female
  • Genes, Dominant
  • Humans
  • Infant
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / genetics
  • Language Development Disorders / blood
  • Language Development Disorders / genetics*
  • Male
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Myosin Type I / genetics
  • Syndrome


  • Codon, Nonsense
  • Intracellular Signaling Peptides and Proteins
  • MYO1F protein, human
  • Microtubule-Associated Proteins
  • RASIP1 protein, human
  • DNA
  • Adenosine Triphosphatases
  • Myosin Type I
  • ATPases Associated with Diverse Cellular Activities
  • FIGN protein, human
  • SRCAP protein, human

Grant support