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Frequent cleft lip and palate in families with pathogenic germline CDH1 variants
Pathogenic and likely pathogenic (P/LP) germline variants in the tumor suppressor gene CDH1 (E-cadherin) result in increased lifetime risk of diffuse-type gastric cancer and lobular breast cancer. CDH1 variants are also associated with hereditary cleft lip and palate (CLP), the mechanism of which is...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554356/ https://www.ncbi.nlm.nih.gov/pubmed/36246616 http://dx.doi.org/10.3389/fgene.2022.1012025 |
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author | Green, Benjamin L. Fasaye, Grace-Ann Samaranayake, Sarah G. Duemler, Anna Gamble, Lauren A. Davis, Jeremy L. |
author_facet | Green, Benjamin L. Fasaye, Grace-Ann Samaranayake, Sarah G. Duemler, Anna Gamble, Lauren A. Davis, Jeremy L. |
author_sort | Green, Benjamin L. |
collection | PubMed |
description | Pathogenic and likely pathogenic (P/LP) germline variants in the tumor suppressor gene CDH1 (E-cadherin) result in increased lifetime risk of diffuse-type gastric cancer and lobular breast cancer. CDH1 variants are also associated with hereditary cleft lip and palate (CLP), the mechanism of which is not well understood. We sought to determine the prevalence of CLP in families who carry P/LP CDH1 variants. Patients with P/LP CDH1 variants who were enrolled in a prospective clinical trial were reviewed (NCT03030404). The cohort included 299 individuals from 153 families that had 80 unique P/LP variants in CDH1. The rate of CLP was 19% (29/153) in families reporting CLP in at least one family member, and 2.7% (8/299) among individuals with confirmed germline CDH1 P/LP variants. There were 22 unique variants in CDH1 among the 29 families that reported CLP, or a CLP rate of 27.5% per variant (22/80). 10 of the variants were not previously reported to be associated with CLP. We observed that 24% (7/29) of CLP-associated gene variants involved large-scale (≥1 exon) deletions. Among families with CLP, 69% (20/29) had a member diagnosed with gastric cancer, and 79% (23/29) had a member with breast cancer, which were similar to rates observed in non-CLP families (p >0.3 for both). Our analysis suggests that the prevalence of CLP in families with germline CDH1 P/LP variants was high in this large cohort, and there was no genotype-phenotype pattern. Genetic testing for CDH1 variants should be considered in families with CLP and history of either diffuse-type gastric or lobular breast cancer. |
format | Online Article Text |
id | pubmed-9554356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95543562022-10-13 Frequent cleft lip and palate in families with pathogenic germline CDH1 variants Green, Benjamin L. Fasaye, Grace-Ann Samaranayake, Sarah G. Duemler, Anna Gamble, Lauren A. Davis, Jeremy L. Front Genet Genetics Pathogenic and likely pathogenic (P/LP) germline variants in the tumor suppressor gene CDH1 (E-cadherin) result in increased lifetime risk of diffuse-type gastric cancer and lobular breast cancer. CDH1 variants are also associated with hereditary cleft lip and palate (CLP), the mechanism of which is not well understood. We sought to determine the prevalence of CLP in families who carry P/LP CDH1 variants. Patients with P/LP CDH1 variants who were enrolled in a prospective clinical trial were reviewed (NCT03030404). The cohort included 299 individuals from 153 families that had 80 unique P/LP variants in CDH1. The rate of CLP was 19% (29/153) in families reporting CLP in at least one family member, and 2.7% (8/299) among individuals with confirmed germline CDH1 P/LP variants. There were 22 unique variants in CDH1 among the 29 families that reported CLP, or a CLP rate of 27.5% per variant (22/80). 10 of the variants were not previously reported to be associated with CLP. We observed that 24% (7/29) of CLP-associated gene variants involved large-scale (≥1 exon) deletions. Among families with CLP, 69% (20/29) had a member diagnosed with gastric cancer, and 79% (23/29) had a member with breast cancer, which were similar to rates observed in non-CLP families (p >0.3 for both). Our analysis suggests that the prevalence of CLP in families with germline CDH1 P/LP variants was high in this large cohort, and there was no genotype-phenotype pattern. Genetic testing for CDH1 variants should be considered in families with CLP and history of either diffuse-type gastric or lobular breast cancer. Frontiers Media S.A. 2022-09-28 /pmc/articles/PMC9554356/ /pubmed/36246616 http://dx.doi.org/10.3389/fgene.2022.1012025 Text en Copyright © 2022 Green, Fasaye, Samaranayake, Duemler, Gamble and Davis. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Green, Benjamin L. Fasaye, Grace-Ann Samaranayake, Sarah G. Duemler, Anna Gamble, Lauren A. Davis, Jeremy L. Frequent cleft lip and palate in families with pathogenic germline CDH1 variants |
title | Frequent cleft lip and palate in families with pathogenic germline CDH1 variants |
title_full | Frequent cleft lip and palate in families with pathogenic germline CDH1 variants |
title_fullStr | Frequent cleft lip and palate in families with pathogenic germline CDH1 variants |
title_full_unstemmed | Frequent cleft lip and palate in families with pathogenic germline CDH1 variants |
title_short | Frequent cleft lip and palate in families with pathogenic germline CDH1 variants |
title_sort | frequent cleft lip and palate in families with pathogenic germline cdh1 variants |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554356/ https://www.ncbi.nlm.nih.gov/pubmed/36246616 http://dx.doi.org/10.3389/fgene.2022.1012025 |
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