Large gene deletion and changes in corneal endothelial cells in a family with choroideremia

We provided the first report of an association between changes in corneal endothelial cells, retina, and choriocapillaris in a choroideremia family.

Four members of an Asian choroideremia family, comprising two affected patients and two carriers, were evaluated. All participants underwent complete eye examinations, including visual acuity (VA), slit-lamp examination, ophthalmoscopy, perimetry, and electrophysiology tests. In addition, images of corneal endothelium were captured with a noncontact specular microscope. Genomic DNA amplification and whole-genome cytogenic array analysis were used to confirm the diagnosis of choroideremia and determine the molecular basis of the phenotype.

In the affected patients, funduscopy revealed characteristic features of RPE and chorioretinal atrophy. The slit-lamp biomicroscopy disclosed unexpected pigmented punctate lesions in the corneal endothelium in one of them. Surprisingly, specular microscopy detected decreased endothelial cell density (ECD) with features of pleomorphism and polymegethism. Genomic DNA analysis revealed large deletion (~4.5 mega base pairs) of the entire CHM gene and encompassed region. In carriers, funduscopy revealed stippling pigmentary change despite normal electrophysiological results. Specular microscopy also disclosed reduced ECD with features of pleomorphism and polymegethism.

To our knowledge, this is the first description of corneal changes in choroideremia patients. The loss of corneal ECD is conspicuous and is accompanied by pleomorphism and polymegethism in this family. The observed changes in corneal endothelium may be associated with larger encompassed regions of the CHM gene defect or dysfunction in the blood-aqueous barrier. It warrants further investigation and clarification of the pathophysiology and associations between retinal and corneal changes in choroideremia.