J Korean Med Sci.  2022 Jan;37(3):e5. 10.3346/jkms.2022.37.e5.

Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa

• Kim JH
• Han JW
• Choi EW
• Bang JH
• Shin HJ
• Jang MA
• Lee JY
• Choi JN
• Chang HS
• Park TK

• KMID: 2524894
• DOI: http://doi.org/10.3346/jkms.2022.37.e5

Abstract

Background
To investigate the clinical findings of choroideremia patients and perform genetic analysis by whole-exome sequencing (WES).
Methods
A total of 94 patients initially diagnosed with retinitis pigmentosa (RP) at another hospital, and who visited our hospital for genetic analysis by WES, were included in the study, along with 64 family members. All subjects underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity, slit lamp examination, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FAG), visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT).
Results
In six male patients with suspected choroideremia, extensive retinal pigment epithelium (RPE) and severe loss of choroid were observed in the fundus, but not in the macula. CHM gene mutation was confirmed in five patients. A novel single nucleotide variant at a splice site was observed in one patient. OCT showed marked thinning of the outernuclear layer and choroid, except in the macula. FAF showed a small area of hyperfluorescence in the posterior pole. In addition, characteristic interlaminar bridges were observed in four patients. On FAG, hypofluorescence was seen up to the far-peripheral retina in five patients.
Conclusion
Of the 94 patients initially diagnosed with RP, CHM mutation was identified in five (5.3%) by WES. Choroideremia should be considered as a differential diagnosis of RP. WES would be useful for identifying the causes of hereditary retinal disease.

Keyword

Choroideremia; Retinitis Pigmentosa; Whole-Exome Sequencing

Figure

• 

  Fig. 1 Wide field color fundus photography of the right and left eyes of a patient with advanced choroideremia.Wide field color fundus photographs show granular and lumpy material, chorioretinal atrophy, and a yellow-whitish sclera in peripheral and peripapillary regions. RPE and choroid remain in only a small area of the macula.RPE = retinal pigment epithelium.

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  Fig. 2 Multimodal imaging of a male choroideremia patient. (A) Color fundus photography shows granular material in the mid-peripheral fundus, chorioretinal atrophy, and preservation of the posterior pole. (B) FAF showed a small area of hyperfluorescence in the posterior pole, in line with the results of color fundus photography shown in (A). (C) FAG revealed hypofluorescence up to the far-peripheral retina, with prominent choroidal vessels.FAF = fundus autofluorescence, FAG = fluorescein angiography.

• 

  Fig. 3 Representative OCT images of choroideremia patients. OCT shows marked atrophy of the RPE, except in the macula, with intraretinal cysts, ORT (arrowhead), and ILB (arrow). Marked thinning of the ONLs was observed and the choroid was virtually absent, both of which are hallmarks of choroideremia.OCT = optical coherence tomography, RPE = retinal pigment epithelium, ORT = outer retinal tubulation, ILB = interlaminar bridge, ONL = outer nuclear layer.

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