New gene for rare inherited paralysis may aid other spinal cord res...( Fink has no direct financial interest ...)

Fink and Rainier have been looking at chromosome 15 for nearly eight years, after discovering that this region contained a mutant HSP gene. Rainier had narrowed the search to a very small region of chromosome 15, and carefully analyzed genes in this region as potential candidates. Meanwhile, Nicholls and his lab had been searching for genes in the same stretch of DNA.

Sharing of information and materials between the two laboratories resulted in the discovery that NIPA1 mutations cause this particularly severe form of HSP. In their paper, the researchers describe the gene and its encoded protein, as well as clinical analysis of affected subjects. The participation of 105 elderly men and women from a U-M Institute of Gerontology registry enabled this study, allowing the investigators to determine the range of normal variations of the new gene.

The affected members of the Iraqi family living in Michigan and the family from Arkansas are among the nearly 400 HSP patients that Fink and his U-M colleagues see each year. The U-M Neurogenetic Disorders Clinic is the largest clinical and research program for HSP and related disorders in the nation, and one of few that offer comprehensive evaluation, including genetic counseling.

The two families are not related, so the researchers believe that the same mutation occurred spontaneously in both, and likely causes the disease in other families and even in patients who have no family history of the disease.

Although more study is needed to understand exactly how the single-nucleotide mutation leads to a dysfunctional protein and thereby to the disabling symptoms of HSP, Fink and his colleagues feel that they have a good chance of unraveling the mystery. They're working to develop a mouse model of this form of HSP, which will enable further studies of potential drug- and cell-based therapies.

Until this research yields n
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
25-Sep-2003