Biomedical Frontiers: Winter 1994, Vol.1, No.2
The Wilson's Disease Gene

A recent payoff from the CPMC Chromosome 13 Genome Project Team has been the identification of the gene causing Wilson's disease, a disorder in which patients cannot excrete copper. Though Wilson's disease is rare, the gene provides clues to normal human copper metabolism, a subject about which little is known and now finally can be investigated. Dr. T. Conrad Gilliam, associate professor of genetics & development in psychiatry at the New York State Psychiatric Institute at CPMC, led the gene hunt. People with the recessively inherited Wilson's disease, which affects 1 in 100,000 live births, accumulate copper in many organs. The build-up causes neurological damage that can seem like schizophrenia. In the liver, the copper toxicity necessitates a liver transplant or death occurs by early adolescence.

The gene, to be reported in Nature Genetics (in press), appears to code for a protein that transports copper across cell membranes. In addition to chromosome walking and polymorphism studies in 115 American, Sardinian, and Russian families, the gene was found by homology studies. The gene was fished from chromosome 13 because it was homologous to a metal binding gene--studied by Dr. Rudolph Tanzi at Massachusetts General Hospital--and to the X-chromosome linked Menkes' Syndrome gene found in January 1993. The Menkes' gene also codes for a copper transport protein which, when mutant in patients causes copper-dependent enzymes to shut down because they lack the metal.