An in-depth study of the genomes of the members of a family who all share a common ancestor has revealed a genetic cause for premature ovarian failure (POF). The same study also suggests for the first time in medical history that POF and azoospermia, the condition of having few if any motile sperm in semen, are quite likely the male and female versions of the same genetic disorder.
The research, headquartered at the University of California, Los Angeles / Spanish National Research Council (UCLA/CSIC), involved collaboration with colleagues from Spain, France, and Israel. The report of the study was published in The New England Journal of Medicine and the journal, Human and Molecular Genetics.
The family in the study is of Middle Eastern descent, from a region where it is traditional for distant family members, such as cousins, to marry. Four women in the family have POF and are infertile.
When the DNA sequences of the infertile women in the family were compared to the DNA sequences of the fertile members of the family, a specific region of chromosome 7q21 was found to be the area of concern. In the infertile women, the gene known as STAG3 was found to carry a mutation that resulted in deletion or loss of genetic code that links together the DNA inherited from the father with the DNA inherited from the mother. This broken link renders the STAG3 gene nonfunctional.
The mutation that the CSIC research team discovered on the STAG3 gene can be passed from the father or from the mother. When a child receives mutated STAG3 genes from both parents, sterility occurs. In the family in the study, the infertile women carried mutated STAG3 genes from both parents while their fertile extended family members inherited just one copy of the gene mutation, coming from either their mother or from their father.
To strengthen their findings, the CSIC research team replicated their study using lab mice specially bred to carry the STAG3 gene mutation. The findings in the lab were the same as the findings in the family: the female mice getting the mutated STAG3 gene from both parents were infertile.
Alberto M. Pendas, a member of the research team, says, "Now, the analysis of this STAG3-deficient mouse has enabled us to corroborate that is a cause of female sterility and a very strong candidate for male infertility."
Source: Caburet, Sandrine, PhD, et al. "Mutant Cohesin in Premature Ovarian Failure." The New England Journal of Medicine. Massachusetts Medical Society. Mar 6, 2014. Web. Mar 23, 2014.