Congenital vertebral malformation is a series of significant health problems affecting a large number of populations. It may present as an isolated condition or as a part of an underlying syndromes occurring with other malformations and/or clinical features. Disruption of the genesis of paraxial mesoderm, somites or axial bones can result in spinal deformity. In the course of somitogenesis, the segmentation clock and the wavefront are the leading factors during the entire process in which TBX6 gene plays an important role. TBX6 is a member of the T-box gene family, and its important pathogenicity in spinal deformity has been confirmed. Several TBX6 gene variants and novel pathogenic mechanisms have been recently revealed, and will likely have significant impact in understanding the genetic basis for CVM. In this review, we describe the role which TBX6 plays during human spine development including its interaction with other key elements during the process of somitogenesis. We then systematically review the association between TBX6 gene variants and CVM associated phenotypes, highlighting an important and emerging role for TBX6 and human malformations.
Keywords: TBX6; congenital scoliosis; congenital vertebral malformation; somitogenesis; vertebrate segmentation.