Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783448710995247104
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
work_keys_str_mv AT kimyonggoo amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT youhyejin amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT parkshinhae amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimmansoo amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT chaehyojin amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT parkjoonhong amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT jekarldongwook amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimjiyeon amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kwonahlm amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT choihayoung amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimyeojae amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT paekarome amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT leeahwon amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimjungmin amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT parkseonyoung amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimyonghwan amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT jookeehyoung amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT leejooyoung amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT jungjongsun amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT chungsohyang amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT mokjeewon amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimmyungshin amutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimyonggoo mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT youhyejin mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT parkshinhae mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimmansoo mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT chaehyojin mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT parkjoonhong mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT jekarldongwook mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimjiyeon mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kwonahlm mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT choihayoung mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimyeojae mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT paekarome mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT leeahwon mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimjungmin mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT parkseonyoung mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimyonghwan mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT jookeehyoung mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT leejooyoung mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT jungjongsun mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT chungsohyang mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT mokjeewon mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy
AT kimmyungshin mutationinznf143asanovelcandidategeneforendothelialcornealdystrophy