Authors
I. M. Krzyzewska, Universiteit van Amsterdam
S. M. Maas, Universiteit van Amsterdam
P. Henneman, Universiteit van Amsterdam
K. V.D. Lip, Universiteit van Amsterdam
A. Venema, Universiteit van Amsterdam
K. Baranano, Kennedy Krieger Institute
A. Chassevent, Kennedy Krieger Institute
E. Aref-Eshghi, Western University
A. J. Van Essen, Universitair Medisch Centrum Groningen
T. Fukuda, Hamamatsu University School of Medicine
H. Ikeda, National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders
M. Jacquemont, CHU la Reunion-Groupe Hospitalier Sud Reunion
H. G. Kim, Qatar Biomedical Research Institute
A. Labalme, CHU de Lyon
S. M.E. Lewis, Children's and Women's Health Centre of British Columbia
G. Lesca, CHU de Lyon
I. Madrigal, Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS
S. Mahida, Kennedy Krieger Institute
N. Matsumoto, School of Medicine
R. Rabionet, Universitat de Barcelona
E. Rajcan-Separovic, Children's and Women's Health Centre of British Columbia
Y. Qiao, Children's and Women's Health Centre of British Columbia
B. Sadikovic, Western UniversityFollow
H. Saitsu, Hamamatsu University School of Medicine
D. A. Sweetser, Massachusetts General
M. Alders, Universiteit van Amsterdam
Publication Date
11-4-2019
Journal
Clinical Epigenetics
URL with Digital Object Identifier
10.1186/s13148-019-0749-3
Abstract
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.
