STARS

We have performed an exome sequencing of a family of patients with an aggregation of very severe forms of ankylosing spondylitis. We identified a rare missense variant of the BbSp gene carried by all family members with a severe form of the disease. The corresponding amino acid is highly conserved across mammals, attesting its functional importance. This gene is involved in bone metabolism and we wish to confirm its causal role in the ossifications of AS by i) exome sequencing of 200 patients with a severe form of SA ii) phenotypic study in CT and histology of an animal mouse model carrying the same mutation of the murine BbSp gene; we will look for ossifications of the spine and entheses iii) the use of a cell culture model of chondrocytes and osteoblasts from these mice to understand the functional consequences of this mutation on their maturation and cellular functions.