PTPN11

The PTPN11 gene carries the instructions for making a protein called SHP-2. This protein helps generate signals within cells that affect how cells function and how often they divide. During embryonic development, this protein plays a critical role in the development of the heart, blood cells, bones, and several other tissues.

The PTPN11 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.

Noonan syndrome - caused by mutations in the PTPN11 gene

More than 50 mutations causing Noonan syndrome have been identified in the PTPN11 gene. Most of these mutations change one of the building blocks (amino acids) used to make the SHP-2 protein. These changes are believed to cause the protein to be continuously active, rather than switching on and off in response to other cellular proteins. The constant activation disrupts the regulation of systems that control cell functions such as growth and division. This misregulation can result in the heart defects, bleeding problems, skeletal abnormalities, and other features of Noonan syndrome.

cancers - increased risk from variations of the PTPN11 gene

Gene mutations can be acquired during a person's lifetime and are present only in certain cells. This type of mutation is called a somatic mutation, and it is not inherited. Somatic mutations in the PTPN11 gene can increase the risk of developing a type of blood cancer called juvenile myelomonocytic leukemia. These mutations cause the SHP-2 protein to be continuously active. Overactivity of the SHP-2 protein disrupts the regulation of pathways that control the production of immature blood cells. As a result, certain white blood cells are overproduced, leading to this type of leukemia.

Some studies indicate that somatic mutations in PTPN11 are also associated with other blood disorders including chronic myelomonocytic leukemia, myelodysplastic syndrome, nonsyndromic acute myeloid leukemia, and acute lymphocytic leukemia.

other disorders - caused by mutations in the PTPN11 gene

Mutations in the PTPN11 gene can cause Noonan-like/multiple giant cell lesion syndrome. This syndrome has many of the same signs and symptoms as Noonan syndrome, but individuals with this disorder also have giant cell lesions (groups of unusually large cells that often have more than one nucleus) that can cause internal or external cysts in bones and soft tissues.

Mutations in the PTPN11 gene can also cause LEOPARD syndrome, also called multiple lentigines syndrome. The acronym LEOPARD stands for lentigines (brown skin spots similar to freckles), ECG abnormalities (measurement of abnormal electrical heart activity), ocular hypertelorism (widely spaced eyes), pulmonary stenosis (narrowing of the artery from the heart to the lungs), abnormalities of genitalia (reproductive organs), retardation of growth (short stature), and deafness. These characteristics vary, however, even among affected individuals in the same family.