FOR IMMEDIATE RELEASE
May 7, 1997
UCSF RESEARCHERS FIND GENE LINKED
TO CONNECTIVE TISSUE DEFECT IN EHLERS-DANLOS SYNDROME
Ehlers-Danlos Syndrome, or EDS, is not a commonly known disorder,
even though several types are listed in the medical books and one in 20,000
people have the disease. Some cases may not be diagnosed because of the
variability in symptoms.
UCSF researchers have discovered that a deficiency in the gene
producing the protein tenascin-X, or TNX, is a cause of EDS. It appears
that this protein has unique functions in the development and strength of
connective tissue.
The UCSF study results were reported Saturday, May 3, at the
combined annual meeting of the American Pediatric Society, Society for
Pediatric Research, and Ambulatory Pediatrics Association in Washington,
DC.
The research finding was based on the results of a skin biopsy from
a 26-year-old man whose symptoms included elastic skin, excessively mobile
joints, easy bruising and poor wound healing--findings typical of EDS. The
patient also had a disorder called congenital adrenal hyperplasia, which is
caused by deficiency of another gene and results in problems in steroid
hormone production.
The TNX gene is a large gene located on chromosome 6. It has been
found to overlap the gene for the 21-hydroxylase gene, whose deficiency
causes congenital adrenal hyperplasia.
"The patient is unique in that he has both TNX deficiency and
21-hydroxylase deficiency. This allowed us to make the connection between
his EDS and the lack of tenascin-X protein production," said James D.
Bristow, MD, assistant professor in the UCSF Department of Pediatrics and
principal investigator of the study.
To understand the genetic links of the disorder, the research team
grew cell cultures from the patient's skin biopsy. They then determined
that these cells did not produce the TNX protein. The same testing
procedures conducted on the young man's parents and sisters found no such
deficiency, however.
"EDS patients often can bend their thumbs back to their wrist bones
and many have frequent dislocations that require surgery. Joint pain is
also common," noted Bristow. In addition, some have skin that appears
"doughy."
Most people with EDS have no recourse for treatment except for
supportive therapy, according to Bristow. Some patients with the common
forms of EDS find they cannot work, and others with more serious forms show
effects such as artery and uterine rupture or eye problems. "Previously
reported types of EDS have been related to mutations in the collagen genes.
TNX deficiency suggests a new mechanism of disease for EDS," he said.
The importance of the UCSF finding is that it provides a new
candidate gene for evaluation in EDS patients. It may also uncover new
clues about the mechanism of the disorder, according to the researchers.
"This research provides the first unequivocal evidence of a
specific function for one of the proteins known as tenascins," said
Bristow.
Co-investigators on the study included Grant H. Burch, MD, first
author and currently assistant professor of pediatrics at the Oregon Health
Science Center in Portland; Yan Gong, MD; Wenbui Liu, MD; Robert Dettman,
PhD; and Walter L. Miller, MD, all of the UCSF Department of Pediatrics.
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