CHM gene

• Overview
• Choroideremia
• References

Overview

Gene (OMIM No.)	CHM (#300390)
Function of gene/protein	Protein: Rab escort protein 1 (REP-1) Expressed ubiquitously throughout the body Supports intracellular trafficking of Rab proteins and modification of their lipid membranes (prenylation) Dysfunction of REP-1 affects protein transport within the photoreceptor cells and phagocytosis of shed outer segments by the RPE
Clinical phenotype (OMIM phenotype no.)	Choroideremia (#303100)
Inheritance	X-linked recessive
Signs	Male patients Progressive diffuse chorioretinal atrophy encroaching the fovea Sclera may be visible in advanced cases Cataract Choroidal neovascularization Cystoid macular oedema Female carriers Range of severity Patchy areas of RPE mottling (mild; common) Smaller, localized areas of chorioretinal atrophy (intermediate) Diffuse chorioretinal atrophy similar to male patients (severe) Earlier onset disease tends to have more severe phenotype
Visual function	Onset of nyctalopia in early childhood Progressive peripheral scotoma over time VA is usually preserved till the late stages before foveal atrophy ensues Legal blindness in the 4th or 5th decade of life Female carriers are usually mildly affected (later disease onset) due to X-inactivation but there are some cases of severe phenotype similar to male patients
Systemic features	Complete/partial deletion of the X chromosome involving the CHM gene can result in: Cognitive issues Sensorineural deafness Cleft lip/palate
Key investigations	FAF: Small island of central hyper-AF with sharply-demarcating borders represent surviving retinal tissue; surrounded by large hypo-AF areas due to chorioretinal atrophy FAF in female carriers with mild disease show fine speckles of hypo-AF throughout the posterior pole OCT: Loss of outer retinal layers and RPE in areas of chorioretinal atrophy; ellipsoid zone is preserved centrally Progressive shortening of EZ length as disease progresses Electrophysiology: rod-cone dystrophy can be observed early in the disease; both responses progressively deteriorate over time Standard perimetry
Molecular diagnosis	Targeted gene panels (retinal) as primary investigation Western blot analysis of leukocytes for REP-1 protein if panel testing is negative and choroideremia is still suspected Whole genome sequencing Cytogenetic testing (microarray or karyotyping) for atypical cases to detect chromosomal deletion
Management	Management of choroideremia
Therapies under research	Research in choroideremia
Further information	Medline Plus

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References

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