Researchers Find Gene For Hair, Tooth And Sweat Gland Development

July 22, 1996

Researchers Find Gene for Hair, Tooth and Sweat Gland Development
(EMBARGOED UNTIL 5 P.M. EASTERN TIME, MONDAY, JULY 29)

Contact: Linda Sage, 314-286-0119

Researchers Find Gene for Hair, Tooth and Sweat Gland Development

St. Louis, July 29, 1996 -- An international research team has isolated a gene involved in hair growth. When faulty, the gene causes an inherited disorder called anhidrotic ectodermal dysplasia (ED). Children and adults with ED have little hair and missing teeth. They also cannot perspire. The gene codes for a new type of protein whose function, when uncovered, may shed light on hair production and tooth development.

The findings are reported in the August issue of Nature Genetics. An accompanying News & Views article notes that the ED gene is "the first cloned gene that is directly associated with human baldness."

There are about 150 ectodermal dysplasia syndromes (EDs). "Because this is the first one for which a gene has been isolated, we hope it will provide an entree into the entire field" says David Schlessinger, Ph.D., head of one of the research groups. Schlessinger is a professor of molecular microbiology, of genetics and of medicine at Washington University School of Medicine in St. Louis, where he directs the Center for Genetics in Medicine. The center has completed a detailed map of the X chromosome.

About 125,000 Americans have ectodermal dysplasia, involving abnormalities in the structure and appearance of the skin and related structures. According to the National Foundation for Ectodermal Dysplasias in Mascoutah, Ill., children with the disorder lead near-normal lives. But they have to be fitted with dentures by about age 3, and those with anhidrotic (lacking sweat glands) ED must take special precautions during hot weather to prevent overheating. The lead authors of the paper are Juha Kere, M.D., Ph.D., now acting professor of medical genetics at the University of Helsinki, Finland, and Anand K. Srivastava, Ph.D., now a scientist at the J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center in South Carolina. Kere and Srivastava performed much of this research while they were in Schlessinger's lab at Washington University.

ED first was reported in 1848. In 1875, Charles Darwin described 10 members of a family in India who had missing teeth, very little hair and dry skin in hot weather. He noted that the tendency to develop the disorder was transmitted from mothers to sons and that women in that family were not affected.

Such an inheritance pattern suggests the gene lies on the X chromosome, of which men have only one copy. The gene later became the first one on chromosome X to be localized by the position of a gross genetic defect called a translocation. In 1986, several research groups confirmed the gene's position on the long arm of X by genetic studies.

Kere moved the research to the molecular level in 1992 by cloning DNA from the ED gene region. The gene itself proved to be unusually difficult to isolate, however.

Srivastava made a breakthrough at Washington University in 1995 when he precisely mapped the starting point of the gene. This led to the isolation of the working parts of the gene by Kere, who had returned to the University of Helsinki in 1993.

Srivastava and two collaborators showed that this gene is faulty in some anhidrotic ED patients. Jonathan Zonana, M.D., at Oregon Health Sciences University in Portland, Ore., and Nick Thomas, Ph.D., at the University of Wales College of Medicine in Cardiff, U.K., confirmed the gene's identity by finding that it contained mutations or deletions in about 10 percent of the DNA samples they had collected from more than 100 ED patients.

Kere also determined where the gene is active in adults. "We found that it is expressed in hair follicles and in the skin cells that make keratin," he says. "It is expressed at lower levels in sweat glands and sebaceous glands, which secrete oil."

The researchers have no clues about the function of the gene, which bears little resemblance to any that has been isolated from any organism. But its structure suggests that it codes for a membrane protein.

"Further work with a mouse model will help explain how this single gene affects these various tissues," Srivastava says.

"The gene clearly operates at an early stage of embryological development of the skin," Schlessinger adds. "We also speculate that it may be necessary throughout life for the continuing health of these skin organelles. So naturally we hope it holds the secret to hair growth."

The research at Washington University was funded by the National Center for Human Genome Research at the National Institutes of Health and by the Juselius Foundation in Finland.
Kere J, Srivastava AK, Montonen O, Zonana J, Thomas N, Ferguson B, Munoz F, Morgan D, Clarke A, Baybayan P, Chen EY, Ezer S, Saarialho-Kere U, de la Chapelle A, Schlessinger D. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein.
Nature Genetics 13(4), 409-416 (1996).

Photographs of children with ED are available from Linda Sage at 314-286-0119.

Juha Kere can be reached at 011-3580-434-6677 or juha.kere@helsinki.fi
(7-hour time difference from U.S. Eastern Time).
Anand Srivastava can be reached at 864-388-1806 or anand@ggc.org
Jonathan Zonana can be reached at 503-494-4448 or zonanaj@ohsu.edu
Nick Thomas can be reached at 011-44-1222-745104 or thomasns@cardiff.ac.uk (5-hour difference).

David Schlessinger will be available after July 30 at 314-362-2744 or 314-362-1199, or call Linda Sage at 314-286-0119 for help with setting up interviews.


Washington University School of Medicine

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