The results of a three-year study published recently in the prestigious American Journal of Human Genetics highlighted the importance of the identification of a gene that plays a major role in sexual development and its contribution to existing knowledge of genes that affect ovarian development and the ovulation process.
The study was led by Dr David Zangen, Head of the Pediatric Endocrinology Unit at the Hadassah University Medical Center and Prof. Ephrat Levy-Lahad, Head of the Medical Genetics Institute at the Shaare Zedek Medical Center, and funded by a research grant from the Israel Science Foundation and the Department of the Chief Scientist of Israel.
The study began three years ago when a teenage girl who had not gone through puberty arrived at Hadassah’s Pediatric Department.
A preliminary examination revealed that the girl had the female genetic code – the XX chromosome structure – and that many of her female relatives suffered from the same condition. In an attempt to locate the defective gene, 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 explained. “Estrogen is a hormone that 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.”
“This 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,” Prof. Levy-Lahad stated. “The specific mutation we discovered probably doesn’t harm men’s fertility, however that gene is also responsible for sperm cell division, and different mutations in that gene could affect male fertility.”
The researchers are now working on further studies related to the possible function of this gene in men and other genes that inhibit ovarian development with the hope of gaining a better understanding of ovarian development and contributing to better-informed medical intervention in the future.
The research group included Dr. Maha Abdulhadi-Atwan and Dr. Abdulsalam Abu Libdeh of Hadassah’s Pediatric Endocrinology Unit; Dr Yotam Kaufman, Sharon Zeligson, Shira Perlberg, Hila Fridman and Paul Renbaum of the Shaare Zedek Genetics Institute; Moein Kanaan of the University of Bethlehem; and Dr Liran Carmel and Ayal Gussow from the Department of Genetics of the Hebrew University of Jerusalem