C19orf12 mutation leads to a pallido-pyramidal syndrome

• Autosomal recessive pallido-pyramidal syndromes are genetically heterogeneous.
• We report a novel C19orf12 mutation leading to pallido-pyramidal syndrome.
• The mutation disrupts a glycine zipper motif crucial for protein-lipid interactions.

Pallido-pyramidal syndromes combine dystonia with or without parkinsonism and spasticity as part of a mixed neurodegenerative disorder. Several causative genes have been shown to lead to pallido-pyramidal syndromes, including FBXO7, ATP13A2, PLA2G6, PRKN and SPG11. Among these, ATP13A2 and PLA2G6 are inconsistently associated with brain iron deposition. Using homozygosity mapping and direct sequencing in a multiplex consanguineous Saudi Arabian family with a pallido-pyramidal syndrome, iron deposition and cerebellar atrophy, we identified a homozygous p.G53R mutation in C19orf12. Our findings add to the phenotypic spectrum associated with C19orf12 mutations.