Is a curved spine (called "scoliosis") found more frequently in people with the 16p11.2 deletion? If it is found more often, how is the TBX6 gene involved?

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There is an higher chance for a curved spine (scoliosis) in children with the 16p11.2 deletion than children without the 16p11.2 deletion.

The 16p11.2 region includes a gene called TBX6. Since 16p11.2 deletion means that this region is missing, a person with a 16p11.2 deletion is also missing a TBX6 gene. However, since we have two of each of our chromosomes, there is still a TBX6 gene on the chromosome 16 which does not have a deletion.  There is a genetic change that can occur in the TBX6 gene, which alone has no effects on health, but if found in a person with 16p11.2 deletion can increase the chance for scoliosis even more.

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What is the TBX6 gene and what does it do? The TBX6 gene is part of the typical 16p11.2 deletion. People with the 16p11.2 deletion have only one copy of the TBX6 gene because the second copy is deleted. In other words, there should be two copies of the TBX6 gene to provide instructions to the body, but people with the deletion are missing one set of instructions.

The TBX6 gene is important for early development of the spine and skeletal muscle, and therefore was thought to be most likely related to scoliosis in children with the deletion.

How is TBX6 involved? To understand if scoliosis is a feature of the deletion, the researchers reviewed genetic testing in 161 children with congenital scoliosis (caused by incorrectly formed vertebrae that are present from birth) to see how many had the deletion 16p11.2. They found that 12 of the 161 children had the deletion (this is about 7.5%).

Interestingly, not everyone with the deletion is found to have scoliosis. In fact, most people with the deletion do not have scoliosis or other problems with the way the spine is formed.  So, why do some people with the deletion have scoliosis and not others? The reason for this is likely due to a certain genetic change on the other TBX6 gene on chromosome 16. This genetic change is natural variation, meaning in most circumstances, it has absolutely no noticeable effect on a person’s health. However, this certain genetic change on one copy of chromosome 16 in combination with the deletion on the other copy seems to greatly increase the chance for scoliosis.

For healthcare providers and researchers

“Our data show that TBX6 null mutations are associated with sporadic congenital scoliosis, and in conjunction with the TBX6 haplotype of T-C-A, these mutations accounted for 9 – 11% of congenital scoliosis cases in the study population with the disorder. TBX6 null mutations and noncoding variants therefore contribute substantively to the complex trait of sporadic congenital scoliosis (Wu, et al., 2015).”