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UW researchers discover gene mutation associated with a form of Charcot-Marie-Tooth disease

Mutation linked to inherited nerve disorder

University of Washington

University of Washington (UW) researchers have found a genetic mutation underlying one of the Charcot-Marie-Tooth disorders. Their results appear in the Jan. 14 edition of Neurology, a journal of the American Academy of Neurology.

Charcot-Marie-Tooth disorders are characterized by nerve degeneration in the hands and lower arms and in the feet and lower legs. The nerve damage leads to muscle weakness and loss of sensation in these parts of the body.

Affecting about 1 in 2,000 people, Charcot-Marie-Tooth disorders are the most common inherited neurological diseases. Different forms of the disease appear as the result of different genetic abnormalities. Charcot-Marie-Tooth-related abnormalities have been located on a number of human chromosomes.

UW researchers decided to study a type of Charcot-Marie-Tooth, known as CMT1C, for which an associated gene or chromosomal defect had not yet been identified. They studied families who had immediate relatives with CMT1C in four or more generations. Blood samples for DNA analysis were taken from affected family members.

In these samples, the researchers found mutations in the LITAF gene (lipopolysaccharide-induced tumor necrosis factor-alpha factor), a gene also referred to as SIMPLE (small integrated membrane proteins of the lysosome/late endosome). This widely expressed gene encodes a protein that may play a part in degrading other proteins. The disease role of the mutated gene in the 1C form of Charcot-Marie-Tooth is unknown. Researchers suspect that the normal LITAF gene may be significant in the degradation of proteins critical to peripheral nerve function, and that the mutated gene may not be able to carry out this function efficiently. Further studies of the mutated LITAF gene may lead to new understandings of peripheral nerve damage.

The discovery of the LITAF mutations could provide a molecular marker for the 1C form of Charcot-Marie Tooth. The researchers also hope the findings will lead to greater understanding of how the LITAF gene functions.


The authors of this study were: Drs. Valerie Street and Bruce Tempel from the UW's Virginia Merrill Bloedel Hearing Research Center and Department of Otolaryngology-Head and Neck Surgery; Drs. Craig Bennett and Phillip Chance, and J.D. Goldy and Andrew Shirk, all from the UW Department of Pediatrics; Drs. K.A. Kleopa and S.S. Scherer from the University of Pennsylvania Department of Neurology, Dr. Thomas Bird from the UW Department of Neurology, and H. Hipe from the Veterans Affairs Puget Sound Health Care System.

The study volunteers were UW Medicine patients and family members of UW patients.

The study was funded by the Muscular Dystrophy Association, the National Institutes of Health, and the Charcot-Marie-Tooth Association, and research funds from the Veterans Affairs Puget Sound Health Care System.

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