Abstract
Purpose: :
To report the histopathologic findings in a confirmed case of choroideremia (CHM). CHM is an X–linked retinopathy caused by mutations in the REP–1 gene, which encodes Rab Escort Protein–1 (REP–1). All mutations reported to date result in deletions or stop codons that lead to truncation of the protein, and loss of function. A 30–year–old male with CHM died in a motor vehicle accident; his eyes were recovered 15 hrs. post–mortem, and subjected to histopathological examination. A brother suffered from CHM and was available for study to confirm the clinical diagnosis by immunoblot analysis and molecular genetic analysis.
Methods: :
Protein derived from white blood cells of the living brother was subjected to immunoblot analysis with an anti–REP–1 monoclonal antibody, 2F1. Direct sequencing of the coding region and adjacent splice sites was undertaken on genomic DNA from the living brother. Histopathological study of the donated eyes was performed. The eyes were fixed, embedded and cut through pupillary–optic nerve plane horizontally.
Results: :
Immunoblot analysis showed that the living brother lacked REP–1. Mutation analysis of genomic DNA from his brother revealed a transition mutation, C to T in exon 6 (R253X) that results in a stop codon that is predicted to truncate the protein product. This mutation has previously been reported in many other presumably unrelated patients with CHM. Histopathologic examination showed in the mid–peripheral fundus: atrophy of the choroid and choriocapillaris, an intact Bruch’s membrane, loss of the RPE and pseudo–rosette formation.
Conclusions: :
Immunoblot analysis and molecular genetic analysis confirmed that the 30–year–old male and his brother suffered from CHM. This case provided an opportunity to study changes in affected eyes prior to end–stage disease.
Keywords: pathology: human • retinal degenerations: hereditary • genetics