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Faulty gene linked to disorders of sexual development

2010-12-04
(Press-News.org) Scientists have discovered that the alteration of a single gene could cause some male embryos to develop as females.

The breakthrough will improve diagnosis and clinical management of patients with disorders of sex development (DSD). These conditions occur when the testis or ovary does not develop properly in the embryo, causing genital abnormalities in one in 4500 babies.

An international team including researchers from the Murdoch Childrens Research Institute and the University of Melbourne identified the gene alteration in a group of patients including two families with several affected members.

The alteration occurred in a gene called MAP3K1, which plays a role in switching on genes that direct the gonad to become a testis. Males normally have one X and one Y chromosome and females have two X chromosomes. But researchers found that the alteration of the MAP3K1 gene disrupted the normal process of testis development, resulting in a male XY embryo developing female characteristics including female genitalia and an overall feminine appearance.

Professor Andrew Sinclair, lead researcher from the Murdoch Childrens Research Institute and the University of Melbourne said the discovery showed the underlying cause of testis failure in these patients, which would help provide a diagnosis and guide clinical management of cases in the future.

"To date, we know of only a small number of genes that are involved in gonad development, and can only diagnose about 20 per cent of DSD patients," he said.

"Based on our study, we believe mutation of the MAP3K1 gene could be responsible for a further 20 per cent of XY DSD cases. This is a major breakthrough as the MAP3K1 gene provides new insights into normal testis development and significantly increases the number of DSD cases we can diagnose in the future."

INFORMATION: The study, published today in the American Journal of Human Genetics, was undertaken in collaboration with the Women's and Children's Hospital, Adelaide, New York University School of Medicine, MRC Mammalian Genetics Unit, UK, Centre Hospitalier Universitaire de Nantes, France.


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[Press-News.org] Faulty gene linked to disorders of sexual development