A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy

Journal of Clinical Medicine
Yonggoo KimMyungshin Kim

Abstract

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 en...Continue Reading

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Methods Mentioned

BETA
PCR
chip
exome sequencing
reverse transcription PCR
Feature Extraction
electrophoresis
Assay
light microscopy
GTPase
transfection

Software Mentioned

GeneMapper
Quantity One
PolyPhen2
AMBER
GeneSpring GX
Multiple Sequence Alignment by Conformational Space Annealing ...
DEVA
GATK
GSEA
GelDoc

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