Familial adenomatous polyposis.
Finlay Macrae1, D du Sart, S Nasioulas
1Department of Colorectal Medicine and Genetics and Familial Cancer Clinic, PO Box 2010, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. finlay.macrae@mh.org.au
Summary
A comprehensive genetic testing strategy effectively identifies most pathogenic germline APC gene mutations in Familial Adenomatous Polyposis (FAP) patients. Remaining cases may involve alternative FAP causes like MYH-associated polyposis or APC mosaicism.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- Familial Adenomatous Polyposis (FAP) is a hereditary condition predisposing individuals to colorectal cancer.
- Accurate identification of germline mutations in the APC gene is crucial for FAP diagnosis and management.
- Existing diagnostic protocols may not capture all pathogenic mutations.
Purpose of the Study:
- To present a robust multimodal screening protocol for identifying pathogenic germline APC gene mutations in FAP patients.
- To investigate potential alternative genetic causes in FAP patients with negative screening results.
Main Methods:
- Utilized a multimodal approach combining complementary techniques.
- Targeted screening for truncating, deletion, and rearrangement mutations in the APC gene.
Main Results:
- The described protocol identifies the vast majority of pathogenic germline APC gene mutations in FAP patients.
- A subset of patients remained without identified APC mutations, suggesting other underlying genetic factors.
Conclusions:
- The multimodal screening protocol is highly effective for detecting common APC gene mutations in FAP.
- Patients negative for APC mutations warrant further investigation for conditions such as MYH-associated polyposis or APC somatic mosaicism.
Related Concept Videos
01:19Appendicitis
Appendicitis is an acute inflammatory condition of the vermiform appendix, most commonly caused by obstruction of its lumen. The appendix is a narrow, blind-ended pouch that extends from the cecum, making it particularly prone to obstruction. Causes include fecaliths, lymphoid hyperplasia (often after viral infections), parasites, tumors, or foreign bodies. This obstruction initiates a cascade of pathological changes.Luminal Obstruction and Early InflammationAfter obstruction, normal mucosal...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:21Inflammatory Bowel Disease V: Surgical Management
Surgical interventions for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are essential in managing symptoms and addressing complications. The selection of surgical procedures is contingent upon the specific conditions and complications that stem from these illnesses.
Here are some common surgical interventions for IBD:
Here are some common surgical interventions for IBD:
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...