title: The defining DNA methylation signature of Floating-Harbor Syndrome.
abstract: 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.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5, Canada.|Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, 401 Smyth Road, Ottawa, K1H 5B2, Canada.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hood
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, 1151 Richmond Street, London, N6A 3K7, Canada.
authors.forename: Laila C
authors.initials: LC
authors.lastname: Schenkel
authors.affiliation: Provincial Medical Genetics Program, BC Women's Hospital and Health Centre, 4500 Oak Street, Vancouver, V6H 3N1, Canada.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Nikkel
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, 1151 Richmond Street, London, N6A 3K7, Canada.|Lawson Research Institute, London Health Sciences Centre, 750 Base Line Road East, London, N6A 5W9, Canada.|Molecular Genetics Laboratory, London Health Sciences Centre, 800 Commissioners Road East, London, N6A 5W9, Canada.|Children's Health Research Institute, 800 Commissioners Road East, London, N6A 5W9, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ainsworth
authors.affiliation: Department of Pathology and Molecular Medicine and Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, L8S 4L8, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, 401 Smyth Road, Ottawa, K1H 5B2, Canada.|Department of Pediatrics, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8L1, Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, 401 Smyth Road, Ottawa, K1H 5B2, Canada.|Department of Pediatrics, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8L1, Canada.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, 1151 Richmond Street, London, N6A 3K7, Canada.|Molecular Genetics Laboratory, London Health Sciences Centre, 800 Commissioners Road East, London, N6A 5W9, Canada.|Children's Health Research Institute, 800 Commissioners Road East, London, N6A 5W9, Canada.
authors.forename: Bekim
authors.initials: B
authors.lastname: Sadikovic
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities / Q000235:genetics; D000015:Abnormalities, Multiple / Q000097:blood / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000097:blood / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D042002:Chromatin Assembly and Disassembly; D018389:Codon, Nonsense; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D004392:Dwarfism / Q000097:blood / Q000235:genetics*; D005145:Face / Q000002:abnormalities*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007805:Language Development Disorders / Q000097:blood / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D024461:Myosin Type I / Q000235:genetics; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D047908:Intracellular Signaling Peptides and Proteins; C562136:MYO1F protein, human; D008869:Microtubule-Associated Proteins; C487329:RASIP1 protein, human; D004247:DNA; D000251:Adenosine Triphosphatases; D024461:Myosin Type I; D000074183:ATPases Associated with Diverse Cellular Activities; C000613810:FIGN protein, human; C119652:SRCAP protein, human