A5007159639- Otitis Media and Relapsing Polychondritis
- Immunodeficiency and Autoimmune Disorders
- Histiocytic Disorders and Treatments
- Vascular Anomalies and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Inflammasome and immune disorders
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Autoimmune Bullous Skin Diseases
- interferon and immune responses
- Atherosclerosis and Cardiovascular Diseases
- Congenital Ear and Nasal Anomalies
- Autoimmune and Inflammatory Disorders Research
- Systemic Lupus Erythematosus Research
Center for Human Genetics
2022-2024
New York University
2022-2024
National Institutes of Health
2021-2023
National Human Genome Research Institute
2020-2023
Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated autoinflammatory disease, may define new disorders.We analyzed peripheral-blood exome sequence data independent of phenotype and inheritance pattern to identify deleterious mutations genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, transcriptome cytokine profiling were performed. CRISPR-Cas9-edited zebrafish...
Objective Somatic mutations in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified having met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize within cohort with RP have not been defined. We undertook this study to define the prevalence and create an algorithm identify genetically confirmed among those RP. Methods Exome targeted...
Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations unique bone marrow (BM) features 16 VEXAS. All were male had a history of severe autoinflammatory rheumatologic somatic mutation (p.Met41). Ten disorders: myelodysplastic syndrome (MDS; 6 16), multiple myeloma (2 monoclonal gammopathy...
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VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a pleiotropic, severe autoinflammatory disease caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. To elucidate pathophysiology, we performed transcriptome sequencing of single bone marrow mononuclear cells and hematopoietic stem progenitor (HSPCs) from patients. HSPCs are biased toward myeloid (granulocytic) differentiation, against lymphoid differentiation VEXAS. Activation...
Abstract Objective Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a complex immune disorder consequence of UBA1 variants. Most reported pathogenic variants are missense or splice site mutations directly impairing the translational start at p.Met41, with recent studies showing that these frequent causes recurrent inflammation in older individuals. Here we aimed to characterize novel variant found two patients clinically presenting VEXAS syndrome. Methods...
Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 and identified a genotype-driven method. This condition affects unrelated men with adultonset inflammatory syndromes association hematologic manifestations of peripheral cytopenia bone marrow myeloid dysplasia. Although vacuolization restricted to erythroid precursors has been patients VEXAS, the detailed clinical histopathological features blood marrows remain unclear....
Background: Somatic mutations in ubiquitin activating enzyme 1 ( UBA1 ) cause a newly defined syndrome known as VEXAS. [1] More than fifty percent of patients currently identified with VEXAS meet diagnostic criteria for relapsing polychondritis (RP). Objectives: To determine the prevalence within cohort RP, to compare their clinical, laboratory, and immunologic features develop clinical algorithm inform genetic screening among RP. Methods: Exome targeted sequencing gene was performed...