Genes contain the intricate instructions for building and maintaining our bodies. Small alterations, known as mutations, can occur within these genetic instructions. While many mutations have no noticeable effect, some can impact health. This article explores the MUTYH gene and the implications of its mutations.
The MUTYH Gene and Its Role
The MUTYH gene, also known as MYH, maintains the integrity of our genetic material. Its primary function is DNA repair, specifically addressing errors that arise during DNA replication. During cell division, DNA strands are copied, and incorrect base pairing can occur due to oxidative damage.
The MUTYH gene product, an enzyme, recognizes and removes a specific damaged DNA base called 8-oxoguanine. If left unrepaired, this damaged base can lead to incorrect base pairings during subsequent DNA replication. By excising this base, the MUTYH enzyme initiates a repair pathway, preventing permanent errors from being incorporated into the DNA sequence. This role establishes MUTYH as a “caretaker” gene, preserving genome stability.
Understanding MUTYH Mutations
A MUTYH mutation is an alteration within the gene’s sequence that impairs its DNA repair function. This compromised ability to correct oxidative DNA damage allows errors to accumulate in the DNA of cells, particularly in rapidly dividing cells like those lining the colon.
Conditions linked to MUTYH mutations follow an autosomal recessive inheritance pattern. This means an individual must inherit two mutated MUTYH gene copies, one from each parent, to develop the condition. Individuals inheriting only one mutated copy are carriers. Carriers do not develop the condition because their single functional gene copy is sufficient for DNA repair, but they can pass the mutated gene to their children.
Health Conditions Associated with MUTYH Mutations
Inheriting two mutated MUTYH gene copies increases the risk for MUTYH-associated polyposis (MAP). MAP is characterized by multiple adenomatous polyps in the colorectal region, varying from a few to hundreds. These benign growths can progress into colorectal cancer if not detected and removed.
The impaired DNA repair in MAP leads to genetic errors in colorectal cells, increasing polyp formation and malignant transformation. Individuals with MAP have a high lifetime risk of developing colorectal cancer, estimated at 70% to 100% without surveillance. They may also have an increased risk for other cancers, including duodenal cancer and, less commonly, sebaceous gland tumors.
Genetic Testing and Medical Management
Genetic testing for MUTYH mutations is considered for individuals with a personal or family history suggestive of MAP. This includes those with multiple colorectal polyps, especially if diagnosed at a younger age, or individuals with early-onset colorectal cancer. Testing identifies if an individual is a carrier (one mutated gene) or has two mutated genes, indicating a MAP diagnosis.
Medical management for MAP focuses on rigorous surveillance to detect and remove polyps early, reducing colorectal cancer risk. This involves regular colonoscopies, often starting in late teens or early twenties. The frequency is determined by the number and type of polyps found. Genetic counseling is also recommended for affected individuals and their families to understand inheritance patterns and implications.