TY  - JOUR
AU  - Aref-Eshghi, E
AU  - Bend, EG
AU  - Hood, RL
AU  - Schenkel, LC
AU  - Carere, DA
AU  - Chakrabarti, R
AU  - Nagamani, SCS
AU  - Cheung, SW
AU  - Campeau, PM
AU  - Prasad, C
AU  - Siu, VM
AU  - Brady, L
AU  - Tarnopolsky, MA
AU  - Callen, DJ
AU  - Innes, AM
AU  - White, SM
AU  - Meschino, WS
AU  - Shuen, AY
AU  - Pare, G
AU  - Bulman, DE
AU  - Ainsworth, PJ
AU  - Lin, H
AU  - Rodenhiser, DI
AU  - Hennekam, RC
AU  - Boycott, KM
AU  - Schwartz, CE
AU  - Sadikovic, B
Y2  - 2020/12/09
Y1  - 2018/11/20
SN  - 2041-1723
UR  - http://hdl.handle.net/11343/253264
AB  - 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.
LA  - English
PB  - NATURE PUBLISHING GROUP
T1  - BAFopathies' DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes
DO  - 10.1038/s41467-018-07193-y
IS  - Nature Communications
VL  - 9
IS  - 1
L1  - /bitstream/handle/11343/253264/PMC6244416.pdf?sequence=1&isAllowed=y
ER  -