Etude in silico des mutations du gène POC5 impliquées dans la maladie de la scoliose

Abstract

Idiopathic scoliosis, a lateral deformity of the spine, remains a major medical concern. Recent research has focused on mutations in the POC5 protein, implicated in this disease. POC5 is a centrosomal protein, which plays an essential role in regulating cell division and tissue morphogenesis. Recently, it was reported that variants (A446T, A455V, A429V, T413A) of POC5 were associated with SIA susceptibility with overexpression of POC5 mRNA in the muscles of scoliotic patients. Accordingly, the aim of our work is to study in silico the impact of these four mutations in the POC5 gene on the protein, using various prediction software programs: I Mutant2.0, Polyphen-2, SIFT, Project HOPE. Mutations in this protein can alter its structure and/or function, thus disrupting the biological processes regulating normal spinal development. Indeed, our analysis revealed a destabilizing effect of the A446T mutation on the protein, while the other three mutations A455V, A429V, T413A were predicted to stabilize POC5. Similarly, all four mutations were predicted to be benign and tolerant, meaning that these substitutions have no impact on protein function, despite physico-chemical changes between some wild-type and mutated amino acids. Variations in the POC5 protein studied may be involved in its interaction with other proteins, or the existence of modifier alleles that could be involved in the expression of scoliosis disease.