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De novo protein-truncating mutations in\n                    <jats:italic>ASXL1<\/jats:italic>\n                    cause Bohring-Opitz syndrome (BOS; OMIM #605039), a rare neurodevelopmental condition characterized by severe intellectual disabilities, distinctive facial features, hypertrichosis, increased risk of Wilms tumor, and variable congenital anomalies, including heart defects and severe skeletal defects giving rise to a typical BOS posture. These BOS-causing\n                    <jats:italic>ASXL1<\/jats:italic>\n                    variants are also high-prevalence somatic driver mutations in acute myeloid leukemia. We used primary cells from individuals with BOS (\n                    <jats:italic>n<\/jats:italic>\n                    = 18) and controls (\n                    <jats:italic>n<\/jats:italic>\n                    = 49) to dissect gene regulatory changes caused by\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations using comprehensive multiomics assays for chromatin accessibility (ATAC-seq), DNA methylation, histone methylation binding, and transcriptome in peripheral blood and skin fibroblasts. Our data show that regardless of cell type,\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations drive strong cross-tissue effects that disrupt multiple layers of the epigenome. The data showed a broad activation of canonical Wnt signaling at the transcriptional and protein levels and upregulation of\n                    <jats:italic>VANGL2<\/jats:italic>\n                    , which encodes a planar cell polarity pathway protein that acts through noncanonical Wnt signaling to direct tissue patterning and cell migration. This multiomics approach identifies the core impact of\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations and therapeutic targets for BOS and myeloid leukemias.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.167744","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T12:00:58Z","timestamp":1681387258000},"source":"Crossref","is-referenced-by-count":15,"title":["Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-6879","authenticated-orcid":true,"given":"Isabella","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Human Genetics,"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA."},{"name":"Department of Computational Medicine, UCLA, Los Angeles, 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