Andrew Robson, Svetlana Z Makova, Syndi Barish, Samir Zaidi, Sameet Mehta, Jeffrey Drozd, Sheng Chih Jin, Bruce D Gelb, Christine E Seidman, Wendy K Chung, Richard P Lifton, Mustafa K Khokha, Martina Brueckner
Genomic analyses of patients with congenital heart disease (CHD) have identified significant contribution from mutations affecting cilia genes and chromatin remodeling genes; however, the mechanism(s) connecting chromatin remodeling to CHD is unknown. Histone H2B monoubiquitination (H2Bub1) is catalyzed by the RNF20 complex consisting of RNF20, RNF40, and UBE2B. Here, we show significant enrichment of loss-of-function mutations affecting H2Bub1 in CHD patients (enrichment 6.01, P = 1.67 × 10-03 ), some of whom had abnormal laterality associated with ciliary dysfunction...
July 9, 2019: Proceedings of the National Academy of Sciences of the United States of America