Scientists identify the gene for familial dysautonomia, a degenerative neurological disorder

January 10, 2001

In the March issue of The American Journal of Human Genetics, two groups report that mutations in the IKBKAP gene, encoding the protein IKAP, cause Familial Dysautonomia (FD). Two single base pair mutations in this gene account for nearly 100% of FD cases, and this finding will revolutionize genetic testing for this devastating disorder.

FD is almost exclusively found in people of Ashkenazi Jewish origin, and it is estimated that 1 out of every 32 people in this population carry an FD mutation. People with two mutant copies of the IKBKAP gene show poor development of and degeneration of the sensory and autonomic nervous systems. The symptoms in these affected individuals include: abnormal sweating, hypertension, difficulty feeding and sucking, gastrointestinal dysfunction, and insensitivity to pain. FD is fatal; only 50% of patients reach age 30 years.

The major FD mutation, which accounts for 99.5% of disease chromosomes, results in aberrant splicing of the IKBKAP RNA and thus the loss of one of the coding regions for the IKAP protein. A second, much less common mutation was found to cause a single amino acid change in a putative regulatory region of the protein. Together, these mutations are believed to account for all of the Ashkenazi Jewish cases of FD. With this finding, genetic testing for FD will become very effective and much less expensive.

The function of IKAP is not well understood, but the discovery that IKBKAP is involved in FD opens wide the doors for experimentation that will hopefully someday provide a cure.
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For the full text of these articles, "Tissue-specific expression of a splicing mutation in the IKBKAP gene causes Familial Dysautonomia" by Susan Slaugenhaupt et al. and "Familial Dysautonomia is caused by mutations of the IKAP gene" by Sylvia Anderson et al., please contact The American Journal of Human Genetics at http://www.ajhg.org.

For further information, contact the corresponding authors of these articles: Dr. James Gusella, Dept. of Molecular Neurogenetics, MGH East, Room 6214, 149 13th St., Charlestown, MA 02129, Phone 617-726-5724, Fax 617-726-5736, Email gusella@helix.mgh.harvard.edu.

Dr. Berish Rubin, Dept. of Biological Sciences, Larkin Hall 160, Fordham University, Bronx, NY 10458, Phone 718-817-3642, Fax 718-817-3645, rubin@fordham.edu.

Much of the work that led to the discovery of the gene for FD was supported by the Dysautonomia Foundation, Inc., 633 Third Ave. 12th floor, New York, NY 10017. Phone 212-949-6644.

This research was also funded by Dor Yeshorim, The Committee for Prevention of Jewish Diseases.

Contributed by: Kate Beauregard, The American Journal of Human Genetics. Phone: (404)712-9985, Email: kbeaure@emory.edu

The American Journal of Human Genetics

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