A new gene, HMGCS1, causes stiff spine syndrome

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.

 

HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model. Dofash LNH, Miles LB, Saito Y, et al. Brain. 2024 Nov.