The discovery of Genetic Mutation in TTLL11 Gene (which leads to ciliary defects and is associated with idiopathic scoliosis in a five-generation UK Family) will allow us to screen children of a scoliosis parent, to identify those who have inherited this gene and are therefore at risk of developing scoliosis.
Genetic mutation in TTLL11 Gene leads to ciliary defects and is associated with idiopathic scoliosis in a five-generation UK family. See Chart B
Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional spinal curvature which affects about 3% of the general population. There is a strong genetic component. The Marfan Trust funded Louise Ocaka in her laboratory research supervised by Dr Aragon-Martin and Dr. Anne Child, to study a large UK family with dominantly inherited scoliosis. Louise found the location of the gene on chromosome 9 and successfully submitted this as her PhD thesis. Several years later, the project was taken up again by another PhD student, Miss Hélène Mathieu who is working between our research unit and the University of Montreal, supervised there by Professor Florina Moldovan. She has successfully pursued this gene and discovered that a mutation in TTLL11 contributes to the scoliosis in affected members of this family.
The University of Montreal research unit managed to introduce this gene into a zebrafish model and produced scoliosis in the zebrafish. This confirms that this gene can cause scoliosis.
How Does it Work
In the embryonic period, cilia which are small hair-like attachments on specialised cells, have a role in wafting fluid flow which provides a nourishment to developing bones especially growth plates in the spine. They also have a role in patterning left-right development, which is impaired in scoliosis patients. Moreover, another ciliary gene POC5 can cause scoliosis in humans.
The mutation in TTLL11 in this family leads to abnormal ciliary development which results in shorter cilia, which are ineffective. Moreover, spinal deformity was observed in zebrafish model, once a mutation in the zebrafish TTLL11 was introduced.
The impact of this finding will allow us to screen children of a scoliosis parent, to identify those who have inherited this gene and therefore are at risk of developing scoliosis. They should be observed at frequent intervals especially during the rapid adolescent growth phase when the curve usually develops. Thus, treatment with bracing or spinal surgery when necessary can be offered at the optimal time.
In future, further work may lead us to discover medication or gene therapy which can halt this abnormal development of the spine.
Photo by Holger Link on Unsplash