A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.
Hallervorden-Spatz syndrome (HSS) is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals iron deposits in the basal ganglia. In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, Huntington disease and human immunodeficiency virus (HIV) encephalopathy, in which pathologic accumulation of iron in the brain is also observed. Thus, understanding the biochemical defect in HSS may provide key insights into the regulation of iron metabolism and its perturbation in this and other neurodegenerative diseases. Here we show that HSS is caused by a defect in a novel pantothenate kinase gene and propose a mechanism for oxidative stress in the pathophysiology of the disease.
Zhou
B
B
Howard Hughes Medical Institute and Departments of Medicine and Pediatrics, University of California, Parnassus & Third Avenues, U-426, San Francisco, California 94143, USA.
Westaway
S K
SK
Levinson
B
B
Johnson
M A
MA
Gitschier
J
J
Hayflick
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D017173:Caenorhabditis elegans; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D018387:Codon, Initiator / Q000235:genetics; D004252:DNA Mutational Analysis; D004331:Drosophila melanogaster; D005808:Genes, Recessive; D006801:Humans; D007501:Iron / Q000378:metabolism; D051379:Mice; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009928:Organ Specificity; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000201:enzymology* / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D020161:Physical Chromosome Mapping; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D009626:Terminology as Topic
D018387:Codon, Initiator; D007501:Iron; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase