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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 course1. Histologic study reveals iron deposits in the basal ganglia2. In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease3, Alzheimer disease4, Huntington disease5 and human immunodeficiency virus (HIV) encephalopathy6, 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.

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Figure 1: Localization of the HSS gene region.
Figure 2: Sequence of PANK2 and comparison with other eukaryotic pantothenate kinase genes.
Figure 3: Expression and function of PANK2.

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We are grateful to the many individuals, families and clinicians (J.P. Harpey, M. Shevell, M. Piñeda, G. Kurlemann, J. Coppeto, J. Jankovic, S. Davis, H. Hattori, K. Sethi, M. Pandolfo, L. Angelini, N. Nardocci, A. Malandrini, J. Penzien, G. Mortier, M. Hoeltzenbein, J.A.Urtizberea, M.A.M. Salih, D. Buckley, C. Haenggeli, A. Bottani, B. Beinlich, J. Østergaard, S. Bundey, F. Stogbauer, K. Nørgaard Hansen, J. Guimarães, C. Yalcinkaya, A. Feigenbaum, Z. Liptai, J. Carlo, P. Blasco, A. Zimmerman, R. Cilio, E. Bertini, G. Worley, U. Thyen, J. Molineuvo, M. Melis, G. Cossu, J. Menkes, K. Hollódy, A. Barrett, S. Simpson, C. Schrander-Stumpel, H. Chaabouni, R. Gatti, H. Topaloglu, M. Nigro, F. Hisama, N.R.M. Buist, B. Ben-Ze'ev, A. Macaya, B. Korf, P. Heydemann, S. Abbs, R. Robinson, L. Shinobu, E. Dooling, P. Wheeler, P. Rosman, W. Wasiewski, P. Castelnau, P. Evrard, R. Haslam, M. Filocamo, M. Karwacki, T. Kmieæ, S. Frucht, T. Konishi, M. Regina Reyes, M. Al-Mateen, K. Weidenheim, M. Delgado, S. Johnsen, S. Golembowski, W. Ondo, S. Bohlega, R. Bustamante, O. Fernandez, M. Wiznitzer, H. Morgan, I. Butler, T. Babb, D. Sanderson, M. Williams, C. Harding, R. Steiner, S. Toor, E. Thompson, J. MacKenzie, J. Clyman and D. Fornoff) who contributed to this study. We thank T. Taylor, H. Payami, M. Litt, A. Malone, S. Bae, M. Gunthorpe, H. Consencgo, E. Stewart, S. Packman, the Oregon Health and Science University MMI Sequencing Core, and the Hallervorden–Spatz Syndrome Association. This work was supported by a grant from the National Eye Institute and the Sandler Neurogenetics Center at the University of California, San Francisco. J.G. is an investigator with the Howard Hughes Medical Institute.

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Correspondence to Susan J. Hayflick.

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Zhou, B., Westaway, S., Levinson, B. et al. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 28, 345–349 (2001).

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