A genome-wide DNA methylation signature for SETD1B-related syndrome.
Por:
Krzyzewska IM, Maas SM, Henneman P, Lip KVD, Venema A, Baranano K, Chassevent A, Aref-Eshghi E, van Essen AJ, Fukuda T, Ikeda H, Jacquemont M, Kim HG, Labalme A, Lewis SME, Lesca G, Madrigal I, Mahida S, Matsumoto N, Rabionet-Janssen R, Rajcan-Separovic E, Qiao Y, Sadikovic B, Saitsu H, Sweetser DA, Alders M and Mannens MMAM
Publicada:
4 nov 2019
Resumen:
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.
Filiaciones:
Krzyzewska IM:
Amsterdam UMC, Department of Clinical Genetics, Genome Diagnostics laboratory Amsterdam, Reproduction & Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Maas SM:
Amsterdam UMC, Department of Pediatrics, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Henneman P:
Amsterdam UMC, Department of Clinical Genetics, Genome Diagnostics laboratory Amsterdam, Reproduction & Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Lip KVD:
Amsterdam UMC, Department of Clinical Genetics, Genome Diagnostics laboratory Amsterdam, Reproduction & Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Venema A:
Amsterdam UMC, Department of Clinical Genetics, Genome Diagnostics laboratory Amsterdam, Reproduction & Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Baranano K:
Kennedy Krieger Institute, Department of Neurogenetics, 801 N. Broadway, Rm 564, Baltimore, MD, 21205, USA
Chassevent A:
Kennedy Krieger Institute, Department of Neurogenetics, 801 N. Broadway, Rm 564, Baltimore, MD, 21205, USA
Aref-Eshghi E:
Department of Pathology and Laboratory Medicine, Western University, 800 Commissioner's Road E, London, ON, N6A 5W9, Canada
van Essen AJ:
University Medical Centre Groningen, University of Groningen, Department of Medical Genetics, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
Fukuda T:
Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan
Ikeda H:
National Epilepsy Centre, NHO, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan
Jacquemont M:
Department of medical genetics, CHU La Reunion-Groupe Hospitalier Sud Reunion, La Reunion, France
Kim HG:
Neurological Disorder Center Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar
Labalme A:
Department of medical genetics, Hospices Civils de Lyon, Bron, France
Lewis SME:
Department of Medical Genetics, Children's & Women's Health Centre of British Columbia University of British Columbia, C234-4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada
Lesca G:
Department of medical genetics, Hospices Civils de Lyon, Bron, France
Madrigal I:
Biochemistry and Molecular Genetics Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Center for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain
Mahida S:
Kennedy Krieger Institute, Department of Neurogenetics, 801 N. Broadway, Rm 564, Baltimore, MD, 21205, USA
Matsumoto N:
Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004, Japan
Rabionet-Janssen R:
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, av diagonal 643, 08028, Barcelona, Spain
Rajcan-Separovic E:
Department of Medical Genetics, Children's & Women's Health Centre of British Columbia University of British Columbia, C234-4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada
Qiao Y:
Department of Medical Genetics, Children's & Women's Health Centre of British Columbia University of British Columbia, C234-4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada
Sadikovic B:
Department of Pathology and Laboratory Medicine, Western University, 800 Commissioner's Road E, London, ON, N6A 5W9, Canada
Saitsu H:
Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan
Sweetser DA:
MassGeneral Hospital, Division of Medical Genetics and Metabolism, 175 Cambridge St, Suite 500, Boston, Massachusetts, 02114, USA
Alders M:
Amsterdam UMC, Department of Clinical Genetics, Genome Diagnostics laboratory Amsterdam, Reproduction & Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Mannens MMAM:
Amsterdam UMC, Department of Clinical Genetics, Genome Diagnostics laboratory Amsterdam, Reproduction & Development, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Open Access
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