Disorders of sex development (DSDs) affect approximately one in every 2000 live births. One such DSD is 46,XY gonadal dysgenesis (46,XY DSDs), also known as Swyer syndrome. Harry Ostrer, M.D., and colleagues previously showed that mutations in the MAP3K1 gene are one of the most common causes of 46,XY DSDs. They found that MAP3K1 mutations give the expressed protein new functions that override the normal testes-determining pathway. In their new study, published online on January 4 in Human Molecular Genetics, they show how those mutations alter MAP3K1’s structure and function and describe a previously uncharacterized domain of the protein. Their research reveals two distinct mechanisms by which MAP3K1 mutations co-opt the normal male sex-determining pathway. These findings can offer people with 46,XY DSDs greater insight into their disorder. Dr. Ostrer is professor of pathology and of pediatrics at Einstein.
Posted on: Wednesday, February 06, 2019