Genetic approach

One of the major discoveries of the researchers supported by the Foundation, the outcome of an unprecedented collaboration between two teams (Professor Patrick Edery in Lyon and Professor Florina Moldovan in Montreal), is the identification of a familial variant of idiopathic scoliosis, in particular the mutation of the POC 5 gene. This work has made it possible to :

• Identify a familial variant
• Codify a centriolar protein
• Highlight the important role of cilia

In a zebrafish model, the expression of this gene has produced fish with scoliotic deformities (albeit without alterations to bone elements).
These results have validated the role of POC5 in the development of idiopathic scoliosis.

Dr Guillaume Dugué’s work (CNRS Paris) began with the mutation of the Poc5 gene, in order to study neurodevelopmental disturbances and determine whether they were at the root of idiopathic scoliosis. This research, carried out on mice with the POC5 gene alteration, established that POC5 is probably essential for cilia formation.
They showed : 

• Tissue disorganization in the lung and retina.
• At cellular level: the presence of the mutant POC5 gene induces a reduction in osteoblast cell proliferation (i.e. cells responsible for bone formation) and mineralization.

In the Netherlands, work is in progress by Prof. René Castelein and Steven de Reuver (UCM Utrecht). It focuses on the 22q11.2 deletion syndrome as a new human genetic model for idiopathic scoliosis.
It is based on the fact that the deformation takes place in the intervertebral disc and that this plays an essential role in the initiation and progression of scoliosis.
The team’s hypothesis is that children who develop scoliosis have pre-existing alterations to the intervertebral disc. 50% of patients with 22q deletion syndrome develop scoliosis.
40 children will take part in the study, the results of which are expected in 2028.

Prof. Serge Zakine (Paris Hospitals) and Dr. Laura Marie-Hardy (La Pitié – Salpétrière) are conducting a comprehensive exome analysis of families with idiopathic scoliosis. In other words, the team will study the genetic code of scoliosis patients from the same family.

In Montreal (CHU Sainte Justine, Montreal, Canada), Prof. Alain Moreau’s team is leading an epigenetics project aimed at detecting RNA molecules (microRNA) that can predict the risk of scoliosis progression via blood analysis.
As a result of his work, miR-NORα2 expression is higher in patients with a high risk of deviation progression.