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Marco Mura, MD; Christina Sereda, BS; Monica M. Jablonski, PhD; Ian M. MacDonald, MD; Alessandro Iannaccone, MD, MS

Arch Ophthalmol. 2007;125(8):1107-1113.

Objective  To report the clinical, functional, and in vivo microanatomic characteristics of a family with choroideremia with a deletion of the entire gene that encodes for the Rab escort protein 1 (CHM).

Methods  We performed clinical examination, flash electroretinography (ERG), light- and dark-adapted perimetry, and optical coherence tomography; reviewed medical records; and obtained the medical history of the proband and 3 other family members.

Results  At 4 years of age, the proband had a hypopigmented fundus and retinal pigment epithelium mottling, and dark-adapted ERGs were reduced. Severe retinal pigment epithelium and choriocapillaris atrophy developed by 6 years of age, paralleled by a lesser ERG decline. Optical coherence tomography findings showed normal neural retinas overlying mild changes in the retinal pigment epithelium and thinned neural retina with impaired lamination, yet the neural retina was fairly preserved over retinal pigment epithelium and choriocapillaris atrophy. The carrier mother had diffuse elevation of 650-nm dark-adapted thresholds.

Conclusions  Deletion of the CHM gene causes severe choroideremia. Results of serial ERGs and fundus examinations documented progression first of rod and then of cone disease. Fundus appearance deteriorated rapidly, in excess of the severity of the ERG decline. Optical coherence tomography findings explained this observation, at least in part.

Clinical Relevance  To our knowledge, this is the earliest clinical, microanatomic, and ERG longitudinal phenotypic documentation in molecularly characterized choroideremia and the first documentation of impaired dark-adapted cone function in carriers. The preservation of the neural retina has mechanistic, prognostic, and therapeutic implications.

Author Affiliations: Retinal Degeneration and Ophthalmic Genetics Service, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis (Drs Mura, Jablonski, and Iannaccone); and Department of Ophthalmology, Ophthalmic Genetics Laboratory, University of Alberta, Edmonton (Ms Sereda and Dr MacDonald). Dr Mura is now with the Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

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