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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Ophthalmology, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Shih-Yun
SY
Lee
Department of Ophthalmology, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.
Wei-Kuang
WK
Yu
Department of Ophthalmology, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Po-Kang
PK
Lin
D000328:Adult; D015794:Choroideremia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004247:DNA / Q000032:analysis*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D004728:Endothelium, Corneal / Q000473:pathology*; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012160:Retina / Q000503:physiopathology; D012189:Retrospective Studies; D014792:Visual Acuity
D004247:DNA
choroideremia; endothelium; keratopathy