Genetic switch may explain ‘intersex disorder’

WASHINGTON - In some families, a child is born as a son, but develops physically as a female, although she may not menstruate, and her brothers and male cousins may have underdeveloped or ambiguous genitalia.

Now, experts at NYU Langone Medical Center have identified a gene that appears to be an important switch in determining whether the biological program for the development of gender will go according to plan, or if, when mutated, will cause a glitch in the program.

The discovery allows researchers to explain the cause of so-called ‘intersex’ conditions.

“MAP3K1 may hold the key to understanding how these various genes are connected,” said Harry Ostrer, director of the Human Genetics Program at the Centre.

Ostrer and collaborators in England, Australia, and France, spent nine years searching for the gene responsible for disorders of sex determination in two families, one in France and the other in New Zealand.

Some of the women in the study with the Y chromosome had only partially developed ovaries, an overdeveloped clitoris, and excessive hair, while others had tumours in their ovaries.

Some of the men had a urethral opening on the underside of their penis or had an abnormally small penis. Some were also infertile

All of these individuals had a normal SRY gene, leading the researchers to suspect that MAP3K1 may influence the activity of that gene.

To better understand the prevalence and identify new genes and pathways, Ostrer is setting up a national consortium to sequence the genomes of affected individuals and their parents.

The study appears in the December 2, 2010, issue of the American Journal of Human Genetics. (ANI)