Genomic sequencing helps find treatment for rare genetic skin disorder
2023
University of California, San Diego, USA
Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high. The researchers evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 (STAT4). Primary skin fibroblast and cell-line assays were used to define the functional nature of the genetic defect. The researchers also assayed gene expression using single-cell RNA sequencing of peripheral-blood mononuclear cells to identify inflammatory pathways that may be affected in DPM and that may respond to therapy. Gain-of-function variants in STAT4 caused DPM in the studied families. The JAK inhibitor ruxolitinib attenuated the dermatologic and inflammatory phenotype in vitro and in the affected family members.
Variant STAT4 and response to ruxolitinib in an autoinflammatory syndrome
Lori Broderick
Added on: 09-14-2023
[1] https://www.nejm.org/doi/10.1056/NEJMoa2202318[2] https://www.drugtargetreview.com/news/110105/genomic-sequencing-helps-find-treatment-for-rare-genetic-skin-disorder/?utm_source=Email+marketing&utm_medium=email&utm_campaign=DTR+-+Industry+Insight+-+Quantum+-+01.09.2023&utm_term=Computational+tool+gets+more+out+of+multi-omics+data&utm_content=https%3a%2f%2femails.drugtargetreview.com%2frussellpublishinglz%2f&gator_td=mIEcIc9i81kCKVEhzhGoua2AdBgsh3MXlma4DaxbM%2bxK7rKyR%2fQcxk8ybkHB1l%2bRXEvytgBCnnivdmqswbwYTxn4iGykbFmGXXK7dz8FnJzV82Okhr4PBfh1smePTncFC5cYRgtu%2f2Az8umlaHaYwOrkQf3awJMA0VuCviYYObU2xCPqj4rl%2b6sSM5T5exVI%2fzk%2b0uf1Z1EzIpnMw8X8kEumOE8bMB8%2f1hAmVz6Yx%2fw%3d
