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Series GSE84940 Query DataSets for GSE84940
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
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.
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.
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
Submission date Jul 28, 2016
Last update date Mar 11, 2017
Contact name Anthony J. Aldave
Organization name Stein Eye Institute, UCLA
Department Ophthalmology
Lab Cornea Genetics Laboratory
Street address 200 Stein Plaza DSERC 3-143
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL22253 Agilent-079141 PPCD1-3_loci G4126A 8X60 array (Probe name version)
Samples (8)
GSM2254429 PPCD Proband 4
GSM2254430 PPCD Proband 5
GSM2254431 PPCD Proband 10
BioProject PRJNA335716

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84940_RAW.tar 141.2 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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