Analysis of <italic>KERA</italic> in four families with cornea plana identifies two novel mutations.

Abstract: Purpose: To identify the molecular genetic cause in four families of various ethnic backgrounds with cornea plana. Methods: Detailed ophthalmological examination and direct sequencing of the <italic>KERA</italic> coding region in five patients of Czech and Turkish origin and their available family members. Results: Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887‐1G>A in <italic>KERA</italic> were detected in two affected siblings of Czech origin. <italic>In silico</italic> analysis supported the pathogenicity of both variants. The second proband of Czech origin harboured c.835C>T; p.(Arg279*) in a homozygous state. Homozygous mutations c.740A>G; p.(Asn247Ser) and c.674C>T; p.(Ile225Thr) were identified in the Turkish probands, both born out of consanguineous marriages. Observed ocular phenotypes were typical of cornea plana with the exception of one Czech patient who also had marked thinning and protrusion in the superior part of the left cornea (mean keratometry 47.2 D). No corneal endothelial cell pathology was found by specular microscopy in seven eyes, in three eyes visualization of the posterior corneal surface was unsuccessful. Conclusion: <italic>KERA</italic> mutation c.740A>G has been identified to date in three different populations, which makes it the most frequently occurring mutation in patients with cornea plana. Marked corneal thinning and ectasia are a very rare finding in this disorder and longitudinal follow‐up needs to be performed to determine its potential progressive nature. [ABSTRACT FROM AUTHOR]