Novel genetic mutations found in posterior polymorphous corneal dystrophy

This study reports on two novel mutations identified in two Czech probands with posterior polymorphous corneal dystrophy (PPCD) 3.

The authors used Scheimpflug imaging technology, specular microscopy and direct sequencing of the ZEB1 coding region to examine four Czech probands with PPCD3.

They identified two novel mutations within ZEB1: c.2617dup in exon 8 in a 22-year-old woman, considered to be most likely de novo in origin, and c.698dup in exon 6 in a 20-year-old man. The first patient had mild changes consistent with PPCD and bilateral BCVA of 1.00. The corneal phenotype of the patient in the second case was more severe, with BCVA of 0.40 OD and 0.05 OS.

Both probands had abnormally steep corneas with increased pachymetry values but no pattern indicative of keratoconus. Specular microscopy in both patients revealed reduced endothelial cell density. Both probands had a history of surgery for inguinal hernia; the male patient also reported hydrocele.

The authors conclude that nucleotide changes within the coding region of ZEB1 underlie the pathogenesis of PPCD in 4 of 23 Czech probands (17 percent) examined in this and other studies. The cumulative de novo ZEB1 mutation rate was at least 14 percent.

They conclude that in order to further elucidate the pathological mechanism of PPCD3 caused by haploinsufficiency of ZEB1, a greater knowledge and understanding of the targets of this protein is required.