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

Lookup NU author(s): Andrew Curtis, Constanze Fey, Dr Christopher Morris, Professor Laurence Bindoff, Professor Patrick Chinnery, Dr Margaret Jackson, Dr William Barker, Emeritus Professor David Bates, Dr Ann Curtis, Professor Sir John Burn

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Abstract

We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's 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 'neuroferritinopathy'.


Publication metadata

Author(s): Curtis ARJ, Fey C, Morris CM, Bindoff LA, Ince PG, Chinnery PF, Coulthard A, Jackson MJ, Jackson AP, McHale DP, Hay D, Barker WA, Markham AF, Bates D, Curtis A, Burn J

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2001

Volume: 28

Issue: 4

Pages: 350-354

Print publication date: 01/01/2001

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng571

DOI: 10.1038/ng571

PubMed id: 11438811


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