The researchers discovered a rare change in the DNA of two eastern Missouri families with a history of a condition called X-linked recessive idiopathic hypoparathyroidism (XLHPT): a portion of the X chromosome, a human sex chromosome, has been removed and replaced by a copy of a much larger section of genetic material from chromosome 2. Alterations of such large regions of genetic code that stably pass from one generation to the next are generally rare and have never before been observed in the human X chromosome.
The study was led by scientists at Oxford University in England and included researchers from Washington University School of Medicine and Shriners Hospital for Children in St. Louis.
In the long term, the disorder's links to blood calcium levels and parathyroid hormone secretion may someday help scientists seeking to develop new treatments for osteoporosis. For now, though, the findings almost bring to a close a decades-long investigation into the disorder that has plagued two Missouri families for generations.
"So far, XLHPT has only been observed in these two eastern Missouri families and it only affects males--the females are carriers," says Michael Whyte, M.D., professor of medicine, pediatrics and of genetics at Washington University School of Medicine. "Seizures and death within a month of birth is a dramatic set of symptoms, so if this problem had ever developed anywhere else in the world, it seems likely that it would have been reported."
The findings appear in the October issue of The Journal of Clinical Investigation.
XLHPT has likely affected family members at least since the 19th century and was initially described in 1960 by Virginia Peden, a faculty member at Saint Louis University. Although there initially
Contact: Michael C. Purdy
Washington University School of Medicine