Novel mutations in the ZEB1 gene identified in Czech and British patients with posterior polymorphous corneal dystrophy

Abstract

We describe the search for mutations in six unrelated Czech and four unrelated British families with posterior polymorphous corneal dystrophy (PPCD); a relatively rare eye disorder. Coding exons and intron/exon boundaries of all three genes (VSX1, COL8A2, and ZEB1/TCF8) previously reported to be implicated in the pathogenesis of this disorder were screened by DNA sequencing. Four novel pathogenic mutations were identified in four families; two deletions, one nonsense, and one duplication within exon 7 in the ZEB1 gene located at 10p11.2. We also genotyped the Czech patients to test for a founder haplotype and lack of disease segregation with the 20p11.2 locus we previously described. Although a systematic clinical examination was not performed, our investigation does not support an association between ZEB1 changes and self reported non-ocular anomalies. In the remaining six families no disease causing mutations were identified thereby indicating that as yet unidentified gene(s) are likely to be responsible for PPCD.

Figure 1

Pedigrees of PPCD families with novel mutations in the ZEB1 gene identified in this study. A: Czech family C1 showing a heterozygous single-base duplication c.2324_2325dupA resulting in a frame shift with glutamic acid at codon 776 (p.E776fs). B: Czech family C2 showing a heterozygous single-base pair transition c.2157C>G changing tyrosine at position 719 to a stop codon (p.Y719X). C: British family B1 showing a heterozygous single-base pair deletion c.1124delT resulting in a frame shift with phenylalanine at codon 375 (p.F375fs). D: British family B2 showing a heterozygous four-base pair deletion c.1387_1390delCCTT resulting in a frame shift with proline at codon 463 (p.P463fs).