The compound inheritance of TBX6 causing congenital scoliosis was discovered
A genomewide analysis of copy-number variants was performed in 20 trios (consisting of a person with sporadic congenital scoliosis and two healthy parents). We identified recurrent deletions in proximal 16p11.2 in two persons (Patient XH004 and Patient XH042). Both of these heterozygous deletions were de novo (i.e., absent in the patient’s parents). The association of the 16p11.2 deletion with congenital scoliosis suggested that a gene related to the disorder may be located in the segment of DNA that is deleted: of these genes, TBX6 was considered to be the best candidate. We also analyzed two pedigrees with an affected member and unaffected members who had the same 16p11.2 deletion. In Pedigree SE1, the proband had congenital scoliosis with hemivertebra, whereas the father and sibling had the same deletion but did not have congenital scoliosis. In Pedigree SE2, the deletion in the proband was paternally inherited.