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Pejman Bakhtiari, Ricardo Frausto, Ashley Roldan, Cynthia Wang, Anthony Aldave; Exclusion of Pathogenic Promoter Region Variants and Identification of Novel Nonsense Mutations in ZEB1 in Posterior Polymorphous Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4732.
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© ARVO (1962-2015); The Authors (2016-present)
To report the identification of four novel nonsense mutations in the ZEB1 gene and exclusion of promoter region mutations in individuals without ZEB1 coding region mutations in posterior polymorphous corneal dystrophy (PPCD).
Slit lamp examination and DNA collection was performed for individuals diagnosed with PPCD, and when available, affected and unaffected family members. Genomic DNA prepared from peripheral blood leukocytes and buccal epithelial cells underwent PCR amplification and automated sequencing of the ZEB1 gene and promoter region.
Ten unrelated individuals with PPCD were identified and genomic DNA was collected from each. ZEB1 mutations were identified in 5 of the 10 probands, four of which were novel: p.Ala150fsX36 (spontaneous), p.Arg230fsX7, p.Cys638fsX5 and p.Gly1039fsX6. Screening of the ZEB1 promoter region in 28 PPCD probands without a ZEB1 coding region mutation identified only two known SNPs whose frequency in the affected probands did not differ significantly from that in the general population.
We report four novel frame-shift mutations, one confirmed to be spontaneous, in the ZEB1 gene associated with PPCD, bringing the total number of pathogenic mutations to 23, and the percentage of PPCD associated with ZEB1 mutations to 32%. The absence of ZEB1 promoter region mutations in probands without a ZEB1 coding region mutation indicates that other genetic loci, such as PPCD1, are responsible for the majority of cases of PPCD.
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