Two novel KERA mutations causing cornea plana in a Czech family and associated phenotypes

Abstract

PurposeTo identify the molecular genetic cause in a previously not reported Czech family with the occurrence of cornea plana in two siblings.MethodsDetailed ophthalmological examination and direct sequencing of the KERA coding region in the proband followed by target analysis of the identified mutations in other family members.ResultsThe family was not aware of any consanguinity. Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887‐1G>A in KERA were detected in both affected individuals. The mother was a heterozygous carrier of c.887‐1G>A and the father of c.209C>T. In silico analysis supported the pathogenicity of both mutations. The younger brother, aged 13 years, had typical ocular phenotype of cornea plana with keratometry readings bellow 30 D, shallow anterior chamber, indistinct limbus and central corneal opacity. Corneal endothelial cell morphology was normal in the right eye; in the left eye specular microscopy images could not be taken. In the older brother, aged 20 years, marked thinning with protrusion in the superior part of the left cornea was present resulting into mean keratometry of 47.2 D. No corneal endothelial cell pathology was observed by specular microscopy bilaterally.ConclusionsThe identification of two novel heterozygous mutations in the second Czech family with cornea plana does not support the hypothesis of a founder effect. Marked corneal thinning and protrusion in cornea plana is a very rare finding and longitudinal follow‐up evaluation needs to be performed to determine its possible progressivity.