Identification of six novel mutations in ZEB1 and description of the associated phenotypes in patients with posterior polymorphous corneal dystrophy 3

Ann Hum Genet. 2015 Jan;79(1):1-9. doi: 10.1111/ahg.12090. Epub 2014 Dec 1.


Posterior polymorphous corneal dystrophy 3 (PPCD3) is a rare autosomal dominant disorder caused by mutations in ZEB1. To date all identified disease-causing variants were unique to the studied families, except for c.1576dup. We have detected six novel ZEB1 mutations; c.1749_1750del; p.(Pro584*) and c.1717_1718del; p.(Val573Phefs*12) in two Czech families, c.1176dup; p.(Ala393Serfs*19), c.1100C>A; p.(Ser367*), c.627del; p.(Phe209Leufs*11) in three British families and a splice site mutation, c.685-2A>G, in a patient of Sri Lankan origin. An additional British proband had the c.1576dup; p.(Val526Glyfs*3) mutation previously reported in other populations. Clinical findings were variable and included bilateral congenital corneal opacity in one proband, development of opacity before the age of 2 years in another individual and bilateral iris flocculi in yet another subject. The majority of eyes examined by corneal topography (10 out of 16) had an abnormally steep cornea (flat keratometry 46.5-52.7 diopters, steep keratometry 48.1-54.0 diopters). One proband underwent surgery for cryptorchidism. Our study further demonstrates that PPCD3 can present as corneal edema in early childhood, and that an abnormally steep keratometry is a common feature of this condition. As cryptorchidism has been previously observed in two other PPCD3 cases, its association with the disease warrants further investigation.

Keywords: ZEB1; phenotype; posterior polymorphous corneal dystrophy type 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Codon, Nonsense
  • Corneal Dystrophies, Hereditary / genetics*
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Pedigree
  • Phenotype
  • RNA Splice Sites / genetics
  • Sequence Deletion
  • Transcription Factors / genetics*
  • Young Adult
  • Zinc Finger E-box-Binding Homeobox 1


  • Codon, Nonsense
  • Homeodomain Proteins
  • RNA Splice Sites
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1

Supplementary concepts

  • Corneal Dystrophy, Posterior Polymorphous, 1