Public Release: 

Genes Found For Two Syndromes Involving Skin-Color Disorders

University of Wisconsin Health Science

MADISON, Wis. -- With luck, hard work and the latest technology, researchers at the University of Wisconsin Medical School found genes for two diseases on consecutive days.

The double find is reported in back-to-back papers appearing in the November issue of the journal Nature Genetics.

Involving two relatively rare but often devastating genetic disorders that include abnormal pigmentation, the discoveries are the latest in a series of successful searches for genes producing skin-color problems by UW Medical School Professor of Medical Genetics and Pediatrics Dr. Richard A. Spritz. He and his team previously found genes for the two most common forms of albinism and three other disorders associated with pigmentation abnormalities.

The current discoveries, pertaining to Hermansky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS), will allow Spritz and his colleagues to determine how the genes work, which should point the way to treatment for the illnesses.

Rare in most parts of the world, HPS appears with unusually high frequency in Puerto Rico, afflicting one in every 1,800 individuals there. Although albinism is a key feature of the disease, other life-threatening characteristics--potentially lethal lung, kidney, heart and colon problems--make it a serious concern for clinicians.

CHS produces severe immune deficiency that in its worst form can resemble the cancer lymphoma. Bleeding and neurologic abnormalities are also common, as are the skin-color problems which typically are accompanied by extremely poor vision, abnormal eye movements and sun sensitivity that can lead to high rates of cancer. The rare disorder is not restricted to any particular group; it strikes randomly and usually is fatal.

"We found one mutation on the HPS gene that appears to be common to most or all Puerto Ricans with the disease," said Spritz. "This mutation is easily detected by simple testing, which should pave the way for genetic testing to identify HPS patients and carriers in this high-risk group."

The UW team's search for the CHS gene was made easier by their collaborators' work, which identified the mouse equivalent of the gene. The human CHS gene was found to be extremely large, containing a number of mutations. Further studies surely will identify more defects, he noted.

"Both genes are unique; they produce proteins that are unlike anything we've ever seen before," he said. "This gives us few clues as to how the genes work or the cellular basis of these enigmatic disorders, but makes it all the more likely that they will open up new areas of biology."

Spritz speculated that the proteins produced by the genes may be important components of membranes that surround melanosomes, cellular machinery responsible for pigmentation.


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