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

• Published in: Clinical epigenetics Vol. 11; no. 1; p. 156
• Main Authors: Krzyzewska, I. M., Maas, S. M., Henneman, P., Lip, K. v. d., Venema, A., Baranano, K., Chassevent, A., Aref-Eshghi, E., van Essen, A. J., Fukuda, T., Ikeda, H., Jacquemont, M., Kim, H.-G., Labalme, A., Lewis, S. M. E., Lesca, G., Madrigal, I., Mahida, S., Matsumoto, N., Rabionet, R., Rajcan-Separovic, E., Qiao, Y., Sadikovic, B., Saitsu, H., Sweetser, D. A., Alders, M., Mannens, M. M. A. M.
• Format: Journal Article
• Language: English
• Published: Germany BioMed Central Ltd 04.11.2019; BioMed Central
• Subjects: B cells; Biochemistry; Chromatin; Disabilities; DNA; Epigenetic inheritance; Gene expression; Genes; Genetic aspects; Genomes; Genomics; Histones; Methylation; Methyltransferases; Transferases
• ISSN: 1868-7075; 1868-7083; 1868-7083
• 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.