Endless POFibilities -- April 2001

Scientists Isolate Premature Ovarian Failure Gene

National Institutes of Health (NIH)
National Institute on Aging (NIA)
NIH NEWS RELEASE
Tuesday, January 30, 2001

A genetic mutation appears to produce eyelid defects in newborns and trigger POF decades later. The finding could help researchers decipher how genetic processes during fetal development can have immediate manifestations at birth and also lead to certain age-associated changes later in life. The newly identified gene, called FOXL2, is required for the normal eyelid development in newborns. In women, FOXL2 is also needed to form a full complement of eggs in the ovaries before birth. FOXL2 was isolated from a region of chromosome 3 that had been implicated in families with a history of blepharophimosis and premature ovarian failure. If it is mutated, babies may be born with a drooping eyelid condition called lepharophimosis, and certain women born with this condition may also experience POF.The discovery also may shed light on certain aspects of aging, which may be driven by genetic processes that begin soon after conception. FOXL2 is a transcription factor, meaning it stimulates other genes to turn "on" or "off" in the eyelids and ovaries at appropriate times. A mutation in one of the two copies of this gene disrupts this process, so genes that would normally be activated by FOXL2 remain dormant, inactive genes might be inappropriately activated, or both. As a consequence, affected women may be born with blepharophimosis and may have fewer egg follicles than necessary to sustain a normal reproductive lifespan. In the next phase of research, investigators will likely look for the underlying mechanisms that cause women with this genetic mutation to produce fewer eggs. The mutation, for instance, may arrest normal egg follicle development so that fewer of them form in the ovaries. It’s also possible that egg follicles develop normally, but some action triggered by the mutant FOXL2 unnecessarily destroys many of them. The discovery is the first to pinpoint a gene responsible for POF, said David Schlessinger, Ph.D., chief of the NIA’s Laboratory of Genetics in Baltimore.The gene was cloned by Italian scientists led by Giuseppe Pilia of the University of Cagliari, with the assistance of French researchers and NIA investigators.

>>read complete release at NIH's website

IPOFA Support Group Conference 2001