Macular corneal dystrophy and associated corneal thinning

Area of Science:

• Ophthalmology
• Medical Genetics
• Corneal Diseases

Background:

• Macular corneal dystrophy (MCD) is a rare inherited eye disorder.
• Understanding the genetic basis of MCD is crucial for diagnosis and potential therapies.
• Phenotypic overlap between MCD and keratoconus can complicate diagnosis.

Purpose of the Study:

• To determine the molecular genetic cause of macular corneal dystrophy (MCD) in four probands.
• To investigate phenotypic similarities between MCD and keratoconus.
• To identify novel mutations in the CHST6 gene associated with MCD.

Main Methods:

• Ophthalmological examination and Scheimpflug imaging (Pentacam) were performed.
• Histopathological examination of corneal buttons was conducted.
• Direct sequencing of the CHST6 coding region was used to identify mutations.

Main Results:

• Scheimpflug imaging revealed diffuse corneal thinning and paracentral steepening, mimicking keratoconus.
• No posterior corneal ectasia or regional thinning, differentiating it from typical keratoconus, was observed.
• Homozygous or compound heterozygous CHST6 mutations were identified in all cases, including two novel mutations (c.13C>T; p.(Arg5Cys) and c.289C>T; p.(Arg97Cys)).

Conclusions:

• Localized anterior corneal curvature elevation can occur in MCD without other keratoconus features.
• The study identified further Czech probands with the compound allele c.[484C>G; 599T>G], suggesting its enrichment in this population.
• CHST6 mutations are confirmed as the cause of MCD, with potential diagnostic implications.