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 mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…). 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 enzymeProtéine capable d’activer une réaction biochimique précise. 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.