Neuroferritinopathy

In the Advance Online issue of Nature Genetics, Andrew Curtis and colleagues from the Institute of Human Genetics in Newcastle, UK, describe a new genetic disease that they have named 'neuroferritinopathy'. The neurological disease is characterized by adult-onset degeneration of the basal ganglia and extrapyramidal dysfunction. Affected individuals live within a 40km radius of the home of the earliest founder, a member of a local family from Cumbria, UK. Curtis et al. performed linkage analysis to map the disease gene to chromosome 19q13.3. The disease locus contains the gene encoding ferritin light polypeptide (FTL). In six local patients they found a mutation causing an adenine insertion at position 460, which changes the carboxy-terminal residues of the protein. They found that patients had low serum ferritin levels and ferritin-positive inclusions in the basal ganglia and the brain. Mutations in the iron-responsive element of the FTL gene have been described in hereditary hyperferritemia cataract syndrome and iron metabolism has been linked to neurodegenerative disease in mice.