Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13

T. D. Taylor, M. Litt, P. Kramer, M. Pandolfo, L. Angelini, N. Nardocci, S. Davis, M. Pineda, H. Hattori, P. J. Flett, M. R. Cilio, E. Bertini, S. J. Hayflick

Research output: Contribution to journalArticle

Abstract

Hallervorden-Spatz syndrome (HSS) (OMIM 234200) is a rare, autosomal recessive neurodegenerative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.

Original languageEnglish
Pages (from-to)479-481
Number of pages3
JournalNature Genetics
Volume14
Issue number4
DOIs
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    Taylor, T. D., Litt, M., Kramer, P., Pandolfo, M., Angelini, L., Nardocci, N., Davis, S., Pineda, M., Hattori, H., Flett, P. J., Cilio, M. R., Bertini, E., & Hayflick, S. J. (1996). Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. Nature Genetics, 14(4), 479-481. https://doi.org/10.1038/ng1296-479