Home » Key Clinical Research Articles Global Medical Discovery » Large Gene Deletion and Changes in Corneal Endothelial Cells in a Family With Choroideremia

Large Gene Deletion and Changes in Corneal Endothelial Cells in a Family With Choroideremia

Significance Statement

Choroideremia, a rare X-linked recessive chorioretinal dystrophy, is caused by deletion or mutation of the CHM gene, encoding Ras-associated binding (Rab) escort protein-1 (REP-1). It produces progressive degeneration of the retinal pigmented epithelium (RPE), retinal vessels and choriocapillaris, which corresponds to the typical hypopigmented and atrophic fundi with exposure of choroidal vessels, eventually leaving only scattered small areas of intact choroid. Patients with choroideremia have been reported to have posterior polar cataract, cystoid macular edema, and recurrent uveitis. However, abnormal corneal findings have not been reported. Interestingly, we found decreased endothelial cell density (ECD) with features of pleomorphism and polymegethism in both probands and carriers in a choroideremia family. The changes in corneal endothelium may attribute to their loss of the entire CMH gene, chronic low-grade anterior chamber inflammation, or chronic hypoperfusion of the choroid and ciliary body in choroideremia. This study may provide a new direction to investigate the pathophysiology of choroideremia and the association between retina and corneal changes in chorioretinal dystrophies.

Figure Legend

The clinical images of our patients with choroideremia. There were multiple small punctate endothelial lesions disseminated in the whole cornea (left), and pleomorphism and polymegethism of endothelial cells were shown in specular microscope (right).

Choroideremia - global medical discovery

 

 

 

 

 

 

 

Journal Reference

Invest Ophthalmol Vis Sci. 2015;56(3):1887-93.

Lee SY1, Yu WK2, Lin PK3.

Show Affiliations

1Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City, Taiwan
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan

Department of Ophthalmology, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan

3Department 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

Abstract

PURPOSE:

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 geneand 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.

Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Go To Investigative Ophthalmology & Visual Science

Large Gene Deletion and Changes in Corneal Endothelial Cells in a Family With Choroideremia - global medical discovery

 

 

 

 

 

 

 

About The Author

Shih-Yun Lee, MD, is a clinical instructor in the Department of Ophthalmology, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan. She is currently the Acting Chief in the Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City, Taiwan. Dr. Lee completed her ophthalmology residency and fellowship in Taipei Veterans General Hospital, Taipei, Taiwan. Her special interests include vitreoretinal diseases, pediatric ophthalmology and strabismus.

Po-Kang Lin, MD, PhD, is currently a vitreoretinal specialist in the Department of Ophthaomology, Taipei Veterans General Hospital, Taipei, Taiwan. His research focus on the vitreoretinal diseases and bioelectronics.

 

 

 

 

Genetic research in patients with Choroideremia first reported at Global Medical Discovery the World’s leading source of medical research news: featuring the innovations that will lead to a brighter tomorrow