title: Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease.
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'.
authors: Institute of Human Genetics, 19/20 Claremont Place, Newcastle upon Tyne, NE2 4AA, UK.
authors: A R
authors: AR
authors: Curtis
authors: C
authors: C
authors: Fey
authors: C M
authors: CM
authors: Morris
authors: L A
authors: LA
authors: Bindoff
authors: P G
authors: PG
authors: Ince
authors: P F
authors: PF
authors: Chinnery
authors: A
authors: A
authors: Coulthard
authors: M J
authors: MJ
authors: Jackson
authors: A P
authors: AP
authors: Jackson
authors: D P
authors: DP
authors: McHale
authors: D
authors: D
authors: Hay
authors: W A
authors: WA
authors: Barker
authors: A F
authors: AF
authors: Markham
authors: D
authors: D
authors: Bates
authors: A
authors: A
authors: Curtis
authors: J
authors: J
authors: Burn
mesh_terms: D000328:Adult; D017668:Age of Onset; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D018703:Founder Effect; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage; D005917:Globus Pallidus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D009626:Terminology as Topic
chemical_list: D021122:Protein Subunits; D005293:Ferritins; D007501:Iron