Barker WA

Bates D

Bindoff LA

Burn J

Chinnery PF

Coulthard A

Curtis A

Curtis ARJ

Fey C

Hay D

Ince PG

Jackson AP

Jackson MJ

Markham AF

McHale DP

Morris CM

We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington\u27s disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases in which it correlates with visible pathology, possibly by its involvement in toxic free-radical reactions. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name \u27neuroferritinopathy\u27

Newcastle University E-Prints

Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease

Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease

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