FGFR2

The FGFR2 gene provides instructions for making a protein called fibroblast growth factor receptor 2. This protein is one of several fibroblast growth factor receptors, which are related proteins that are involved in important processes such as cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development.

The FGFR2 protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning allows the FGFR2 protein to interact with specific growth factors outside the cell and to receive signals that help the cell respond to its environment. When growth factors attach to the FGFR2 protein, the receptor triggers a cascade of chemical reactions inside the cell that instruct the cell to undergo certain changes, such as maturing to take on specialized functions. The FGFR2 protein plays an important role in bone growth, particularly during embryonic development. For example, this protein signals certain immature cells in the developing embryo to become bone cells in the head, hands, and feet.

There are at least 13 slightly different versions (isoforms) of the FGFR2 protein. Specific patterns of these isoforms are found in the body's tissues, and these patterns may change throughout growth and development.

Apert syndrome - caused by mutations in the FGFR2 gene

Nearly all cases of Apert syndrome are caused by one of two mutations in the FGFR2 gene. These mutations change single protein building blocks (amino acids) in the FGFR2 protein, which alters the protein's 3-dimensional shape. One mutation replaces the amino acid serine with the amino acid tryptophan at protein position 252 (written as Ser252Trp). The other mutation replaces the amino acid proline with the amino acid arginine at position 253 (written as Pro253Arg). The altered FGFR2 protein appears to cause prolonged signaling, which promotes the premature fusion of bones in the skull, hands, and feet.

Beare-Stevenson cutis gyrata syndrome - caused by mutations in the FGFR2 gene

Beare-Stevenson syndrome can be caused by one of two FGFR2 mutations. In the more common mutation, the amino acid tyrosine is replaced by the amino acid cysteine at position 375 in the protein's chain of amino acids (written as Tyr375Cys). Less commonly, the amino acid serine is replaced by the amino acid cysteine at position 372 (written as Ser372Cys). These mutations appear to overstimulate signaling by the FGFR2 protein, which promotes the premature fusion of bones in the skull.

Crouzon syndrome - caused by mutations in the FGFR2 gene

At least 35 mutations that cause Crouzon syndrome have been identified in the FGFR2 gene. Most of these mutations substitute one DNA building block (nucleotide) for another in the FGFR2 gene. Insertions and deletions of a small number of nucleotides are also known to cause the disorder. These mutations in FGFR2 appear to overstimulate signaling by the FGFR2 protein, which promotes premature fusion of bones in the skull.

Jackson-Weiss syndrome - caused by mutations in the FGFR2 gene

Jackson-Weiss syndrome is caused by one of several mutations that change single amino acids in the FGFR2 protein. Each of these mutations occurs in a region of the FGFR2 protein known as the IgIII domain, which is critical for receiving signals and interacting with growth factors. The mutations appear to overstimulate signaling by the FGFR2 protein, which promotes premature fusion of skull bones and affects the development of bones in the feet.

Pfeiffer syndrome - caused by mutations in the FGFR2 gene

More than 25 mutations that cause Pfeiffer syndrome have been identified in the FGFR2 gene. Several of these mutations change the number of cysteine amino acids in a critical region of the FGFR2 protein known as the IgIII domain. The remaining mutations affect amino acids other than cysteine or result in an FGFR2 protein that is missing one or more amino acids. These mutations appear to overstimulate signaling by the FGFR2 protein, which promotes premature fusion of skull bones and affects the development of bones in the hands and feet.

cancers - associated with the FGFR2 gene

Alterations in the activity (expression) of the FGFR2 gene are associated with certain cancers. The altered gene expression may enhance several cancer-related events such as cell division (proliferation), cell movement, and the development of new blood vessels that nourish a growing tumor.

The FGFR2 gene is abnormally active (overexpressed) in certain types of stomach cancers, and this amplification is associated with a poorer outcome. Abnormal expression of FGFR2 is also found in patients with prostate cancer. A shift in the expression of two specific FGFR2 isoforms, IIIb and IIIc, appears to correlate with prostate cancer progression. This change in expression is complex, however, and varies depending on the type of prostate tumor. More advanced tumors may show an increase in the IIIb isoform, while other prostate tumors show a decrease in IIIb but an increase in IIIc. Altered FGFR2 expression is also associated with ovarian, cervical, pancreatic, and head and neck cancers.

other disorders - caused by mutations in the FGFR2 gene

At least three mutations in the FGFR2 gene have been identified in people with lacrimo-auriculo-dento-digital (LADD) syndrome. This condition is characterized by abnormal development of the lacrimal ducts (which carry tears away from the eyes) and the salivary glands (which produce saliva in the mouth). Additional features of LADD syndrome include abnormally shaped ears, hearing loss, small teeth or a reduced number of teeth, and malformations of the hands and feet, particularly the thumbs.

The mutations responsible for LADD syndrome alter the structure of the FGFR2 protein. Researchers believe that these genetic changes almost completely inactivate the protein, and may interfere with normal FGFR2 signaling. It is unclear how reduced FGFR2 signaling leads to the specific features of LADD syndrome.