Familial adenomatous polyposis (Familial adenomatous polyposis) - Genes APC and MUTYH.

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by the colon and rectum. People with the classic form of the disease can begin to develop multiple non - cancerous tumors in the colon during adolescence. Unless the colon is removed, these polyps become malignant. The average age at which an individual develops colon cancer in the classic form of the disease is 39 years. Some people have a variant of the disease called attenuated familial adenomatous polyposis, in which the growth of polyps is delayed. The average age of onset of cancer for this type of polyposis is 55 years.

In people with the classic form of the disease, the number of polyps increases with age and can develop hundreds of thousands of small polyps in the colon. Also of particular importance noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the lining of the gut and may be caused by surgery to remove the colon. Desmoid tumors tend to recur after surgically removed. Sometimes, in the classical form and in its attenuated variant, are benign and malignant elsewhere in the body, including the duodenum, stomach, bones, skin, and other tissue tumors.

This process is due to mutations in the APC gene and MUTYH. Mutations in the APC gene, located on the long (q) arm of chromosome 5 (5q21-q22), are responsible for the classical and attenuated form of familial adenomatous polyposis. This gene, encoding the APC protein, which plays an important role in various cellular processes that determine whether a cell malignizará, since this gene is a tumor suppressor, regulating cell division cycle.

They have identified more than 700 mutations in the APC gene causing classical and attenuated familial adenomatous polyposis (FAP) types. Most of these mutations lead to the production of an abnormally short, nonfunctional version of the APC protein, affecting the ability of the cell to maintain normal growth and function. Excessive growth of cells as a result of mutations in the APC gene causes colonic polyps. Although most people with mutations in the APC gene will develop colorectal cancer, polyp number and the time period in which depend on the location become malignant mutation in the gene. The most common mutation in the adenomatous polyposis is a family of five nucleotides deletion in the APC gene. This mutation changes the amino acid sequence in the APC protein. Mutations in the APC gene are also responsible for a condition called Turcot syndrome which is closely related with familial adenomatous polyposis, and consists of a combination of colorectal cancer with brain medulloblastoma. Approximately two - thirds of people with Turcot syndrome have mutations in the APC gene.

Mutations in the gene MUTYH, located on the short arm (p) of chromosome 1 (1p34.1) cause the autosomal recessive form of familial adenomatous polyposis. This gene encodes an enzyme called MYH glycosylase, which participates in DNA repair. This enzyme corrects errors introduced when divided cellular DNA. Mutations in this gene affect the ability of cells to correct errors during DNA cleavage. In individuals with autosomal recessive disease, both copies of the gene mutated MUTYH in each cell. Most mutations in this gene result in the production of a MYH glycosylase nonfunctional or weak function. When the repair is altered nucleotide excision in the cell, mutations in other genes accumulate, leading to uncontrolled cell to excessive growth, and possible tumor formation.

Familial adenomatous polyposis may have different patterns of inheritance. When the disease is due to mutations in the APC gene is inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to cause disease. In most cases, an affected person has a parent with the disorder. When the disease is due to mutations in the MUTYH gene is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with familial adenomatous polyposis, by complete PCR amplification of the exons of the APC and MUTYH, respectively, and subsequent sequencing genes.  

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).