Sequencing of the TBX6 Gene in Families With Familial Idiopathic Scoliosis

Study DesignA hypothesis-driven study was conducted in a familial cohort to determine the potential association between variants within the T-box 6 (TBX6) gene and familial idiopathic scoliosis (FIS).ObjectiveTo determine whether variants within exons of the TBX6 gene segregate with the FIS phenotype within a sample of families with FIS.Summary of Background DataIdiopathic scoliosis is a structural curvature of the spine whose underlying genetic etiology has not been established. Idiopathic scoliosis has been reported to occur at a higher rate than expected in family members of individuals with congenital scoliosis, which suggests that the 2 diseases might have a shared etiology. The TBX6 gene on chromosome 16p, essential to somite development, has been associated with congenital scoliosis in a Chinese population. Previous studies have identified linkage to this locus in families with FIS, and specifically with rs8060511, located in an intron of the TBX6 gene.MethodsParent-offspring trios from 11 families (13 trios; 42 individuals) with FIS were selected for Sanger sequencing of the TBX6 gene. Trios were selected from a large population of families with FIS in which a genome-wide scan had resulted in linkage to 16p.ResultsSequencing analyses of the subset of families resulted in the identification of 5 coding variants. Three of the five variants were novel; the remaining 2 variants had previously been characterized and they account for 90% of the observed variants in these trios. In all cases, there was no correlation between transmission of the TBX6 variant allele and FIS phenotype. However, an analysis of regulatory markers in osteoblasts showed that rs8060511 is in a putative enhancer element.ConclusionsAlthough this study did not identify any TBX6 coding variants that segregate with FIS, we identified a variant that is located in a potential TBX6 enhancer element. Therefore, further investigation of the region is needed.