A teenage girl who came to the Hadassah University Medical Center for help when she did not go through puberty, led to the discovery of a gene that plays a major role in ovarian development. The three-year investigation was conducted by a joint team from Hadassah and Shaare Zedek Medical Center, led by Dr. David Zangen, head of Hadassah's Pediatric Endocrinology Unit, and Prof. Ephrat Levy-Lahad, head of the Medical Genetics Institute at Shaare Zedek.
The study results, published in the October issue of the American Journal of Human Genetics, highlighted the discovery's important contribution to existing knowledge of genes that affect sexual development and the ovulation process.
A preliminary examination of the teenager and family members three years ago revealed that she did have the female chromosome structure, yet she and many of her female relatives suffered from the same condition. In an attempt to locate the defective gene causing the abnormality, researchers conducted a detailed analysis of the girl's DNA and a full genetic mapping of two of her family members. The test results pinpointed a mutation found only in the specific gene.
"When this gene is defective, the estrogen activity is affected," Dr. Zangen says. He further explains: "Estrogen is pivotal in female sexual development; any irregularities in the production of the hormone can harm the development of the ovaries. Identifying this gene and this mutation is especially significant as there is currently relatively little understanding of the genes responsible for ovarian development, compared to what we know about testicular development."
Prof. Levy-Lahad notes that the discovery "may have important implications for women whose ovaries do not develop and those with early ovarian failure, which leads to infertility in woman in their 30's." While the specific mutation probably doesn't harm men's fertility, she adds, "the gene is also responsible for sperm cell division, and different mutations in that gene could affect male fertility."
The researchers are now zeroing in on the function of this gene in men as well as other genes that inhibit ovarian development.