Scientists had already suspected that the DAX1 gene played a role in the troubling condition. Now they believe they have proof.
"The evidence we have strongly suggests that DAX1 is the gene responsible for human sex reversal syndrome. Just a simple duplication of the gene in a double dose apparently leads to sex reversal," Robin Lovell-Badge, of the MRC National Institute for Medical Research, told Reuters.
DAX1 lies on the X chromosome. When it duplicates it causes an individual who is genetically male to develop physically as a female. Another gene called Sry, on the Y chromosome, is the main sex gene which determines whether testes or ovaries will develop in the embryo.
Lovell-Badge and researchers at the University of Pavia in Italy conducted experiments on transgenic mice to determine how DAX1 and Sry work. The research offers new insights into how sex is determined and identifies the underlying cause of the disorder.
In a report published in the scientific journal Nature, they showed that the interaction of Sry and DAX1 is vital in the early stages of sex-determination.
"We know that Sry is the gene critical for male development. If it's there you get a male, if it isn't you get a female," Lovell-Badge explained.
"Dax1 and Sry act in the same point in the pathway (chain of events) but in a normal male Sry wins. The normal function of DAX1, we believe, is to ensure that secondary male genes are turned off. It's an anti-male gene."
The XY chromosome configuration determines males and the XX females, but in sex reversal syndrome a male with XY will develop female sex organs or women with XX will have male characteristics.
"In this case with these duplications of the X chromosome including DAX1 the individuals are essentially XY so they should have developed as males but they developed (physically) as females," Lovell-Badge said.
The same things happens with Sry. If you have a mutation in that gene you develop as an XY female. In most cases those with sex reversal syndrome are not aware of the condition until puberty, when they fail to ovulate or have a menstrual cycle. "They are women but they are not fertile," he added.
There are also individuals who are chromosomal females with XX chromosomes but who develop as males. Again, the condition may not be evident until puberty.
Complete sex reversal occurs in about one in 5,000 people and partial reversal, producing a hermaphrodite with both testes and ovaries, happens in about one in 1,000 individuals.
The researchers' work was limited to physical sex reversal, but Lovell-Badge said that since DAX1 was found in other parts of the embryo, including the brain, it could have an affect on sex-specific behavior and might explain why some females feel trapped in a male body or vice versa.