Analysis of KERA in four families with cornea plana identifies two novel mutations

• Published in: Acta ophthalmologica (Oxford, England) England), 2018-02, Vol.96 (1), p.e87-e91
• Main Authors: Dudakova, Lubica, Vercruyssen, Jang Hee J., Balikova, Irina, Postolache, Lavina, Leroy, Bart P., Skalicka, Pavlina, Liskova, Petra
• Format: Article
• Language: English
• Subjects: Cornea; cornea plana; Endothelial cells; Heterozygosity; KERA; Microscopy; Missense mutation; Mutation; novel mutation; Pathogenicity; Pathogens; phenotype; Thinning
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/aos.13484

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 KERA 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 KERA were detected in two affected siblings of Czech origin. In silico 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 KERA 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.