<unk>  is inherited in an autosomal dominant fashion.<unk>  is inherited as an autosomal dominant mutation of the E-cadherin gene (CDH1), which is located on chromosome 16q22.1. Because the condition only conveys significantly increased risk of<unk> , it can be described as having incomplete penetrance. The autosomal dominant nature of the mutations implies that inheriting just one mutated copy of the CDH1 gene is sufficient to induce a disease state. However, in order for<unk>  to arise in these individuals, both copies of the CDH1 gene must be inactive. Therefore,<unk>  is developed through a loss of heterozygosity, in which the one unmutated copy of the CDH1 gene undergoes mutation or inactivation in some cells during the lifetime of the individual. This explains why the majority of individuals with CDH1 mutations will develop clinical apparent<unk> , but some do not. The gene mutated in<unk> , CDH1, codes for the E-Cadherin protein. This protein serves numerous functions in cell to cell interactions, as well as intracellular signaling. Development of<unk> ous cells and malignancy may be related to several of these functions. One major function includes cell-cell adhesion facilitated by E-Cadherin binding. Loss of this function may lead to dedifferentiation of cells and/or unregulated cell growth and replication. Another major function includes binding and sequestering of the beta-catenin transcription factor, keeping it inactive. Loss of this function may lead to overactivity of the transcription factor. Genetic counseling and testing for CDH1 mutations are advised for families meeting the following criteria: * Families with two or more documented cases of<unk><unk><unk>  among first or second degree relatives, with at least one case diagnosed before age 50. * Families with two or more documented cases of lobular breast<unk> s among first or second degree relatives, with or without<unk><unk><unk>  in a first or second degree relative. * Any individual diagnosed with<unk><unk><unk>  before 35 years of age from a low incidence population. Non-CDH1 Forms Although CDH1 is by far the most common gene associated with<unk> , around 11% of cases arise in individuals who are negative for mutations in this gene. No other gene has been proven to cause<unk> , but possible associated genes include CTNNA1, BRCA2, STK11, SDHB, PRSS1, ATM, MSR1, and PALB2.
Hereditary diffuse gastric cancer
Hereditary nonpolyposis colorectal cancer
Juvenile polyposis syndrome
Coeliac disease
Tropical sprue
Attenuated familial adenomatous polyposis
Familial adenomatous polyposis
Serrated polyposis syndrome