Paediatrics Publications
Document Type
Article
Publication Date
11-20-2018
Journal
Nature Communications
Volume
9
Issue
1
First Page
4885
Last Page
4885
URL with Digital Object Identifier
https://doi.org/10.1038/s41467-018-07193-y
Abstract
Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Notes
Originally published in Nature Communications, Vol. 9(1)
https://doi.org/10.1038/s41467-018-07193-y
© 2018 The Author(s)