CHM gene


Gene (OMIM No.)
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.)
  • X-linked recessive
SignsMale 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 featuresComplete/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
Therapies under research
Further information

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  1.  Xue K, Oldani M, Jolly JK, et al. Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia. Invest Ophthalmol Vis Sci. 2016;57(8):3674-3684
  2.  Mitsios A, Dubis AM, Moosajee M. Choroideremia: from genetic and clinical phenotyping to gene therapy and future treatments. Ther Adv Ophthalmol. 2018;10:2515841418817490.
  3.  Jauregui R, Park KS, Tanaka AJ, et al. Spectrum of Disease Severity and Phenotype in Choroideremia Carriers. Am J Ophthalmol. 2019;207:77-86.
  4.  Schwartz M, Rosenberg T. Prenatal diagnosis of choroideremia. Acta Ophthalmol Scand Suppl. 1996(219):33-36
  5.  Yntema HG, van den Helm B, Kissing J, et al. A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. Genomics. 1999;62(3):332-343
  6.  Hariri AH, Velaga SB, Girach A, et al. Measurement and Reproducibility of Preserved Ellipsoid Zone Area and Preserved Retinal Pigment Epithelium Area in Eyes With Choroideremia. Am J Ophthalmol. 2017;179:110-117
  7.  Aleman TS, Han G, Serrano LW, et al. Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study. Ophthalmology. 2017;124(3):359-373
  8.  MacDonald IM, Mah DY, Ho YK, Lewis RA, Seabra MC. A practical diagnostic test for choroideremia. Ophthalmology. 1998;105(9):1637-1640

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Updated on November 30, 2020
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