Researchers have identified a single gene that when mutated may trigger premature menopause. The scientists found the mutant gene in men and women with blepharophimosis, an inherited disorder characterized by droopy eyelids. Women with this disorder are infertile.
In an example of Mother Nature’s often puzzling sense of organization, the normal form of the gene, dubbed FOXL2, orchestrates both ovary and eyelid development. The research group, with members from France, Belgium, and the United States, published its discovery in the February Nature Genetics.
About 1 in 100 women enter menopause early, before age 40. Most cases of early menopause have a genetic basis. The condition, also known as premature ovarian failure, can also result from radiation, chemotherapy, and autoimmunity, in which the immune system mistakenly attacks its own tissues.
Sorting out the importance of any one gene behind early menopause has proven difficult because several genes seem to be involved, explains researcher Guiseppe Pilia of the Universit degli Studi di Cagliari in Italy. The pattern of blepharophimosis inheritance, however, indicated that this condition was probably caused by a mutation in a single dominant gene. Pilia’s research group made it its task to find that mutated gene.
To do that, the researchers used a technique called positional cloning to identify genes having mutations in people with the eyelid abnormality. Further analysis revealed one of these genes that is active specifically in ovary and eyelid tissue. The gene turned out to activate a series of other genes involved in eyelid and ovary development.
The discovery is only the first step, says Pilia, “but in the next few months we should know whether or not FOXL2 is involved in [early menopause].” In any case, Pilia’s group says, knowledge about the genes that FOXL2 activates ought to help researchers better diagnose and understand early menopause.