Abstract
The following 2 novel frameshift mutations within ZEB1 were identified: 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 best-corrected visual acuity of 1.00.
The corneal phenotype of the patient in the second case was more severe, with best-corrected visual acuity of 0.40 OD and 0.05 OS. Corneas of both probands were abnormally steep (keratometry readings, flat >= 47.4 diopters [D] and steep >= 49.2 D) with increased pachymetry values but no pattern indicative of keratoconus.
Specular microscopy in both patients revealed reduced endothelial cell density (range, 1055/mm(2) to 1655/mm(2)). Both probands had a history of surgery for inguinal hernia; the male patient also reported hydrocele.
CONCLUSIONS AND RELEVANCE Nucleotide changes within the coding region of ZEB1 underlie the pathogenesis of PPCD in 4 of 23 Czech probands (17%). The cumulative de novo ZEB1 mutation rate is at least 14%.
Possible involvement of ZEB1 sequence variants not readily identified by direct sequencing of coding regions needs to be further investigated. Our findings also have implications for patient counseling.