PT  - JOURNAL ARTICLE
AU  - Joana Figueiredo
AU  - Soraia Melo
AU  - Patrícia Carneiro
AU  - Ana Margarida Moreira
AU  - Maria Sofia Fernandes
AU  - Ana Sofia Ribeiro
AU  - Parry Guilford
AU  - Joana Paredes
AU  - Raquel Seruca
TI  - Clinical spectrum and pleiotropic nature of <em>CDH1</em> germline mutations
AID  - 10.1136/jmedgenet-2018-105807
DP  - 2019 Apr 01
TA  - Journal of Medical Genetics
PG  - 199--208
VI  - 56
IP  - 4
4099  - http://jmg.bmj.com/content/56/4/199.short
4100  - http://jmg.bmj.com/content/56/4/199.full
SO  - J Med Genet2019 Apr 01; 56
AB  - CDH1 encodes E-cadherin, a key protein in adherens junctions. Given that E-cadherin is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, it is no surprise that deleterious effects arise from its loss of function. E-cadherin is recognised as a tumour suppressor gene, and it is well established that CDH1 genetic alterations cause diffuse gastric cancer and lobular breast cancer—the foremost manifestations of the hereditary diffuse gastric cancer syndrome. However, in the last decade, evidence has emerged demonstrating that CDH1 mutations can be associated with lobular breast cancer and/or several congenital abnormalities, without any personal or family history of diffuse gastric cancer. To date, no genotype–phenotype correlations have been observed. Remarkably, there are reports of mutations affecting the same nucleotide but inducing distinct clinical outcomes. In this review, we bring together a comprehensive analysis of CDH1-associated disorders and germline alterations found in each trait, providing important insights into the biological mechanisms underlying E-cadherin’s pleiotropic effects. Ultimately, this knowledge will impact genetic counselling and will be relevant to the assessment of risk of cancer development or congenital malformations in CDH1 mutation carriers.