An 18-year-old male presents with night blindness since childhood and progressive peripheral visual field loss. Visual acuity is 6/9 OU with constricted fields. Fundus examination reveals extensive peripheral chorioretinal atrophy with a characteristic scalloped edge and bare white sclera visible through atrophic patches, sparing only a small central macular island. The optic disc appears normal. Full-field electroretinography shows severely reduced rod and cone responses. Genetic testing confirms a hemizygous loss-of-function mutation in the CHM gene encoding REP-1 (RAB Escort Protein-1). The structure marked **A** in the diagram shows scalloped choriocapillaris atrophy. Which of the following best explains the pathophysiology underlying this finding in choroideremia?
A. Mutations in the PRPH2 gene lead to photoreceptor outer segment disorganization and secondary choriocapillaris atrophy
B. Deficiency of the retinal pigment epithelium causes primary bone-spicule pigmentation and optic disc pallor
C. REP-1 deficiency impairs RAB geranylgeranylation, leading to defective vesicular trafficking in the RPE and photoreceptors
D. Ornithine aminotransferase deficiency causes hyperornithinemia, resulting in choriocapillaris degeneration
Explanation
Practice similar questions
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.
Why REP-1 deficiency impairs RAB geranylgeranylation is right
Choroideremia is an X-linked recessive dystrophy caused by loss-of-function mutations in the CHM gene on Xq21.2, which encodes REP-1 (RAB Escort Protein-1). REP-1 is essential for the geranylgeranylation of RAB proteins, which are critical for vesicular trafficking in the retinal pigment epithelium and photoreceptors. Deficiency of REP-1 impairs this post-translational modification, leading to defective intracellular trafficking, accumulation of lipofuscin, and progressive degeneration of the choriocapillaris, RPE, and photoreceptors—manifesting as the characteristic scalloped choriocapillaris atrophy marked as A in the diagram (AAO BCSC: Retina; MacDonald IM. Choroideremia Review).
Why each distractor is wrong
Ornithine aminotransferase deficiency: This is the genetic basis of gyrate atrophy, a different autosomal recessive chorioretinal dystrophy characterized by hyperornithinemia and treated with arginine restriction and pyridoxine. It does not cause the scalloped choriocapillaris pattern seen in choroideremia.
PRPH2 gene mutations: These cause pattern dystrophies and some forms of retinitis pigmentosa, characterized by photoreceptor outer segment disorganization and bone-spicule pigmentation. The normal optic disc and scalloped choriocapillaris pattern distinguish choroideremia from PRPH2-related disease.
Primary RPE deficiency with bone-spicule pigmentation: This describes retinitis pigmentosa, which presents with waxy disc pallor and bone-spicule pigmentation. Choroideremia has a normal optic disc and scalloped (not bone-spicule) atrophy, making this distinction critical for differential diagnosis.
