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A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy
Corneal dystrophies (CDs) are a diverse group of inherited disorders with a heterogeneous genetic background. Here, we report the identification of a novel ZNF143 heterozygous missense mutation in three individuals of the same family with clinical and pathological features that are consistent with e...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723187/ https://www.ncbi.nlm.nih.gov/pubmed/31390831 http://dx.doi.org/10.3390/jcm8081174 |
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author | Kim, Yonggoo You, Hye Jin Park, Shin Hae Kim, Man Soo Chae, Hyojin Park, Joonhong Jekarl, Dong Wook Kim, Jiyeon Kwon, Ahlm Choi, Hayoung Kim, Yeojae Paek, A Rome Lee, Ahwon Kim, Jung Min Park, Seon Young Kim, Yonghwan Joo, Keehyoung Lee, Jooyoung Jung, Jongsun Chung, So-Hyang Mok, Jee Won Kim, Myungshin |
author_facet | Kim, Yonggoo You, Hye Jin Park, Shin Hae Kim, Man Soo Chae, Hyojin Park, Joonhong Jekarl, Dong Wook Kim, Jiyeon Kwon, Ahlm Choi, Hayoung Kim, Yeojae Paek, A Rome Lee, Ahwon Kim, Jung Min Park, Seon Young Kim, Yonghwan Joo, Keehyoung Lee, Jooyoung Jung, Jongsun Chung, So-Hyang Mok, Jee Won Kim, Myungshin |
author_sort | Kim, Yonggoo |
collection | PubMed |
description | Corneal dystrophies (CDs) are a diverse group of inherited disorders with a heterogeneous genetic background. Here, we report the identification of a novel ZNF143 heterozygous missense mutation in three individuals of the same family with clinical and pathological features that are consistent with endothelial CD. Ophthalmologic examination revealed diffuse corneal clouding and edema with decreased endothelial cell density. Pathological findings showed increased corneal thickness due to edema of basal epithelial cells and stroma, and abnormal metaplastic endothelium with stratified epithelium-like changes. Patients’ metaplastic corneal endothelial cells expressed predominantly cytokerain 7, cytokeratin 19, and E-cadherin. Although Sanger sequencing did not detect any mutation associated with endothelial CDs, whole exome sequencing identified the ZNF143 c.937G>C p.(Asp313His) mutation as a candidate gene for our patients’ endothelial CD. In-vitro functional studies demonstrated that mutant ZNF143 promoted the mesenchymal-to-epithelial transition; it upregulated the expression of genes associated with epithelialization in human corneal endothelial cells. Additionally, proinflammatory cytokine responsive genes were significantly enriched after mutant ZNF143 transfection, which may contribute to the severe phenotype of the three patients. These findings link a mutation in ZNF143 with endothelial CD for the first time. |
format | Online Article Text |
id | pubmed-6723187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67231872019-09-10 A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy Kim, Yonggoo You, Hye Jin Park, Shin Hae Kim, Man Soo Chae, Hyojin Park, Joonhong Jekarl, Dong Wook Kim, Jiyeon Kwon, Ahlm Choi, Hayoung Kim, Yeojae Paek, A Rome Lee, Ahwon Kim, Jung Min Park, Seon Young Kim, Yonghwan Joo, Keehyoung Lee, Jooyoung Jung, Jongsun Chung, So-Hyang Mok, Jee Won Kim, Myungshin J Clin Med Article Corneal dystrophies (CDs) are a diverse group of inherited disorders with a heterogeneous genetic background. Here, we report the identification of a novel ZNF143 heterozygous missense mutation in three individuals of the same family with clinical and pathological features that are consistent with endothelial CD. Ophthalmologic examination revealed diffuse corneal clouding and edema with decreased endothelial cell density. Pathological findings showed increased corneal thickness due to edema of basal epithelial cells and stroma, and abnormal metaplastic endothelium with stratified epithelium-like changes. Patients’ metaplastic corneal endothelial cells expressed predominantly cytokerain 7, cytokeratin 19, and E-cadherin. Although Sanger sequencing did not detect any mutation associated with endothelial CDs, whole exome sequencing identified the ZNF143 c.937G>C p.(Asp313His) mutation as a candidate gene for our patients’ endothelial CD. In-vitro functional studies demonstrated that mutant ZNF143 promoted the mesenchymal-to-epithelial transition; it upregulated the expression of genes associated with epithelialization in human corneal endothelial cells. Additionally, proinflammatory cytokine responsive genes were significantly enriched after mutant ZNF143 transfection, which may contribute to the severe phenotype of the three patients. These findings link a mutation in ZNF143 with endothelial CD for the first time. MDPI 2019-08-06 /pmc/articles/PMC6723187/ /pubmed/31390831 http://dx.doi.org/10.3390/jcm8081174 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Yonggoo You, Hye Jin Park, Shin Hae Kim, Man Soo Chae, Hyojin Park, Joonhong Jekarl, Dong Wook Kim, Jiyeon Kwon, Ahlm Choi, Hayoung Kim, Yeojae Paek, A Rome Lee, Ahwon Kim, Jung Min Park, Seon Young Kim, Yonghwan Joo, Keehyoung Lee, Jooyoung Jung, Jongsun Chung, So-Hyang Mok, Jee Won Kim, Myungshin A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy |
title | A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy |
title_full | A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy |
title_fullStr | A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy |
title_full_unstemmed | A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy |
title_short | A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy |
title_sort | mutation in znf143 as a novel candidate gene for endothelial corneal dystrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723187/ https://www.ncbi.nlm.nih.gov/pubmed/31390831 http://dx.doi.org/10.3390/jcm8081174 |
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