A novel mutation in SLC39A14 causing hypermanganesemia associated with infantile onset dystonia

BACKGROUND: Mutations in SLC39A14 cause a recessive disorder of manganese (Mn) metabolism that manifests as childhood onset progressive neurodegeneration characterized by parkinsonism and dystonia. METHODS: The present study genetically investigated a case of hypermanganesemia. We describe a family where an affected child with a history of progressive neurodegeneration showed symptoms of dystonia with increased levels of blood Mn and altered signal intensities in globus pallidus and dentate nucleus. Whole exome sequencing was conducted to genetically investigate the pathology in the child, which allowed us to identify a novel homozygous causal mutation in SLC39A14. RESULTS: Insilico modeling of the novel homozygous causal mutation in SLC39A14 predicted that it was deleterious, affecting Mn binding and transportation of metal by transmembrane instability of the protein structure. The clinical features of other reported mutations in SLC39A14 were also reviewed and the clinical spectrum in our case conforms to the described neurological abnormalities. CONCLUSIONS: We conclude that the mutation identified in SLC39A14 in our case is a novel variation linked to recessive disorders of hypermaganesemia and dystonia.