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Status |
Public on Mar 08, 2017 |
Title |
Confirmation of the OVOL2 Promoter Mutation c.-307T>C in Posterior Polymorphous Corneal Dystrophy 1 |
Organism |
Homo sapiens |
Experiment type |
Genome variation profiling by genome tiling array
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Summary |
Purpose: 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. Methods: The promoter and/or coding regions of OVOL2 were 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. Results: OVOL2 screening 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 when compared to the wild-type sequence. Conclusions: The previously identified and presumed pathogenic OVOL2 promoter variant c.-307T>C was identified in the PPCD 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.
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Overall design |
Eight PPCD probands without a ZEB1 protein-coding region pathogenic variant were analyzed for copy number variation within the PPCD1 (chromosome 20) and the PPCD3 (chromosome 10) loci.
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Contributor(s) |
Chung DD, Frausto RF, Aldave AJ |
Citation(s) |
28046031 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 EY022082 |
Identification and Characterization of the Genetic Basis of PPCD |
UNIVERSITY OF CALIFORNIA LOS ANGELES |
ALDAVE |
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Submission date |
Jul 28, 2016 |
Last update date |
Mar 11, 2017 |
Contact name |
Anthony J. Aldave |
E-mail(s) |
Aldave@jsei.ucla.edu
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Organization name |
Stein Eye Institute, UCLA
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Department |
Ophthalmology
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Lab |
Cornea Genetics Laboratory
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Street address |
200 Stein Plaza DSERC 3-143
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City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90095 |
Country |
USA |
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Platforms (1) |
GPL22253 |
Agilent-079141 PPCD1-3_loci G4126A 8X60 array (Probe name version) |
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Samples (8)
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Relations |
BioProject |
PRJNA335716 |