Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

ABSTRACT: SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four pathogenic variants of SOX9 identified in a cohort of patients with congenital vertebral malformations. We report a pathogenic missense variant in the transactivation middle (TAM) domain of SOX9 associated with mild skeletal dysplasia and scoliosis. We isolated a Sox9 mutant mouse with an in-frame microdeletion in the TAM domain (Sox9^Asp272del), which exhibits skeletal dyspla

SUBMITTER: Wang L 

PROVIDER: S-EPMC11789016 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature