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CDH1 Mutation Distribution and Type Suggests Genetic Differences between the Etiology of Orofacial Clefting and Gastric Cancer
Journal article   Open access   Peer reviewed

CDH1 Mutation Distribution and Type Suggests Genetic Differences between the Etiology of Orofacial Clefting and Gastric Cancer

Arthavan Selvanathan, Cheng Yee Nixon, Ying Zhu, Luigi Scietti, Federico Forneris, Lina M. Moreno Uribe, Andrew C. Lidral, Peter A. Jezewski, John B. Mulliken, Jeffrey C. Murray, …
Genes, Vol.11(4), p.391
04/01/2020
DOI: 10.3390/genes11040391
PMCID: PMC7231129
PMID: 32260281
url
https://doi.org/10.3390/genes11040391View
Published (Version of record) Open Access

Abstract

Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least 'likely pathogenic', and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants.
Genetics & Heredity Life Sciences & Biomedicine Science & Technology

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