Expert Rev Clin Immunol. 2025 Oct 28. doi: 10.1080/1744666X.2025.2582490. Online ahead of print.
ABSTRACT
BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease characterized by sterile bone inflammation. While monogenic causes are rare and typically present with early-onset, distinct skin or lytic bone lesions, the contribution of COX-pathway genes remains underexplored. TBXAS1 gene variants are classically associated with Ghosal hematodiaphyseal dysplasia (GHDD), which causes osteosclerosis and hematologic abnormalities.
RESEARCH DESIGN AND METHODS: In this single-center, cross-sectional study, whole exome sequencing first revealed the TBXAS1 variants in the index case, a 6-year-old boy with multifocal CNO and good clinical response to NSAIDs. Afterward, we performed next generation sequencing (NGS) of TBXAS1 gene in a single center CNO cohort.
RESULTS: Among 16 patients within CNO cohort, NGS revealed two siblings with the same variants who also presented with CNO, but without signs of osteosclerosis or hematologic involvement.
CONCLUSIONS: These findings suggest a potential link between TBXAS1 deficiency and a distinct, milder CNO phenotype potentially mediated by the COX pathway. However, it remains uncertain whether TBXAS1 mutations define a new CNO subtype or represent an attenuated form of GHDD. Further functional and genetic studies targeting COX-pathway-related genes are needed to clarify the role of TBXAS1 in the pathogenesis of CNO and to identify novel disease mechanisms.
PMID:41148195 | DOI:10.1080/1744666X.2025.2582490
