Novel ZEB1 mutations and associated posterior polymorphous corneal dystrophy phenotypes

Abstract

Purpose: To identify disease-causing mutations in ZEB1 and to determine genotype-phenotype correlation in patients with posterior polymorphous corneal dystrophy 3 (PPCD3).

Methods: Clinical examination and direct sequencing of ZEB1 coding region in six Czech and two British probands with PPCD was performed.

Results: Three novel mutations, predicted to result in haploinsufficiency, were identified; c.1749_1750del [p.(Pro584*)] and c.1717_1718del [p.(Val573Phefs*12)] in two Czech families and c.1176dup [p.(Ala393Serfs*19)] in one British family. Ocular examination of six molecularly confirmed individuals with PPCD3 revealed that one proband had congenital onset and developed nystagmus later in life. Another affected male presented with corneal edema before the age of 2 years and subsequently underwent repeated keratoplasties in each eye. Abnormal corneal steepening (keratometry readings, flat 46.0 - 50.6 D and steep 45.7 - 54.0 D at 3.0 mm) was present in nine out of ten eyes examined.

Conclusions: PPCD3 may present with corneal edema in early childhood. High corneal steepening is a common feature of PPCD3.

Keywords: 494 degenerations/dystrophies • 604 mutations • 481 cornea: endothelium