An international consortium has reported the discovery of a new gene responsible for rigid spine syndrome (RSS):
- several families with an RSS phenotype but no mutation in the SELENON gene have been studied, either in whole exome or whole genome,
- bi-allelic variants of the HMGCS1 gene were identified in five patients from four unrelated families,
- phenotypically, in addition to SSR, they all shared scoliosis and sometimes severe respiratory insufficiency,
- this gene encodes an enzyme in the mevalonic acid pathway, in the same way as HMGCR and GGPS1,
- functional studies in zebrafish have shown that mevalonic acid supplementation can restore a normal phenotype.