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 testes or ovaries do 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, Melbourne, and 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 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 patients 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."
The study, published today by 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, and Centre Hospitalier
Universitaire de Nantes, France.