Journal article
Confirmation of the OVOL2 Promoter Mutation c.-307T>C in Posterior Polymorphous Corneal Dystrophy 1
PloS one, Vol.12(1), pp.e0169215-e0169215
2017
DOI: 10.1371/journal.pone.0169215
PMCID: PMC5207508
PMID: 28046031
Abstract
To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) in families mapped to the PPCD1 locus and in affected individuals without ZEB1 coding region mutations. The promoter, 5' UTR, and coding regions of OVOL2 was screened in the PPCD family in which linkage analysis established the PPCD1 locus and in 26 PPCD probands who did not harbor a ZEB1 mutation. Copy number variation (CNV) analysis in the PPCD1 and PPCD3 intervals was performed on DNA samples from eight probands using aCGH. Luciferase reporter assays were performed in human corneal endothelial cells to determine the impact of the identified potentially pathogenic variants on OVOL2 promoter activity. OVOL2 mutation analysis in the first PPCD1-linked family demonstrated segregation of the c.-307T>C variant with the affected phenotype. In the other 26 probands screened, one heterozygous coding region variant and five promoter region heterozygous variants were identified, though none are likely pathogenic based on allele frequency. Array CGH in the PPCD1 and PPCD3 loci excluded the presence of CNV involving either OVOL2 or ZEB1, respectively. The c.-307T>C variant demonstrated increased promoter activity in corneal endothelial cells when compared to the wild-type sequence as has been demonstrated previously in another cell type. Previously identified as the cause of PPCD1, the OVOL2 promoter variant c.-307T>C was herein identified in the original family that established the PPCD1 locus. However, the failure to identify presumed pathogenic coding or non-coding OVOL2 or ZEB1 variants, or CNV involving the PPCD1 and PPCD3 loci in 26 other PPCD probands suggests that other genetic loci may be involved in the pathogenesis of PPCD.
Details
- Title: Subtitle
- Confirmation of the OVOL2 Promoter Mutation c.-307T>C in Posterior Polymorphous Corneal Dystrophy 1
- Creators
- Doug D Chung - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of AmericaRicardo F Frausto - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of AmericaAleck E Cervantes - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of AmericaKatherine M Gee - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of AmericaMarina Zakharevich - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of AmericaEvelyn M Hanser - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of AmericaEdwin M Stone - Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaElise Heon - Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, CanadaAnthony J Aldave - Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.12(1), pp.e0169215-e0169215
- DOI
- 10.1371/journal.pone.0169215
- PMID
- 28046031
- PMCID
- PMC5207508
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Grant note
- P30 EY000331 / NEI NIH HHS R01 EY022082 / NEI NIH HHS
- Language
- English
- Date published
- 2017
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983979988502771
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