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Choroideremia

, MD, CM, , PhD, , MSc, and , MD, PhD.

Author Information
, MD, CM
Professor, Department of Ophthalmology and Visual Sciences
University of Alberta
Edmonton, Alberta, Canada
, PhD
Joint Laboratory Head and Associate Professor,Molecular Diagnostics Laboratory
Department of Medical Genetics
University of Alberta
Edmonton, Alberta, Canada
, MSc
Genetic Counsellor, Department of Ophthalmology and Visual Sciences
University of Alberta
Royal Alexandra Hospital
Edmonton, Alberta, Canada
, MD, PhD
Biomedical Sciences
Imperial College School of Medicine
London, United Kingdom

Initial Posting: ; Last Update: February 26, 2015.

Summary

Disease characteristics.

Choroideremia (CHM) is characterized by progressive chorioretinal degeneration in affected males and milder signs in carrier females. Typically, symptoms in affected males evolve from night blindness to peripheral visual field loss, with central vision preserved until late in life. Although carrier females are generally asymptomatic, signs of chorioretinal degeneration can be observed with careful fundus examination. These signs become more readily apparent after the second decade.

Diagnosis/testing.

The diagnosis of CHM can be made clinically, based on the fundus examination and family history consistent with X-linked inheritance. The diagnosis is confirmed with the identification of a pathogenic variant in CHM which encodes the protein REP-1.

Management.

Treatment of manifestations: Surgical correction of retinal detachment and cataract as needed; UV-blocking sunglasses for outdoors; appropriate dietary intake of fresh fruit, leafy green vegetables; antioxidant vitamin supplement as needed; regular intake of dietary omega-3 very-long-chain fatty acids, including docosahexaenoic acid; low vision services as needed; counseling as needed to help cope with depression, loss of independence, fitness for driving, and anxiety over job loss.

Surveillance: Periodic ophthalmologic examination and Goldmann visual field examinations to monitor progression.

Agents/circumstances to avoid: UV exposure from sunlight reflected from water and snow.

Genetic counseling.

CHM is inherited in an X-linked manner. An affected male transmits the pathogenic variant to all of his female offspring and none of his male offspring. A carrier female has a 50% chance of passing the pathogenic variant to her offspring: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will usually not be affected. Carrier testing for at-risk female relatives and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variant has been identified in an affected family member.

Diagnosis

Suggestive Findings

Diagnosis of choroideremia (CHM) should be suspected in individuals with the following findings:

Affected males. The diagnosis of choroideremia (CHM) can be made if the following are present [Roberts et al 2002]:

  • A history of defective dark adaptation. Poor vision in the dark is commonly the first symptom in affected males. Males may not note such symptoms until their early teens.
  • Characteristic fundus appearance. Patchy areas of chorioretinal degeneration generally begin in the mid-periphery of the fundus. The areas of chorioretinal degeneration progress to marked loss of the retinal pigment epithelium and choriocapillaris (inner of the two vascular layers of the choroid that is composed largely of capillaries) with preservation of the deep choroidal vessels, as demonstrated by intravenous fluorescein angiography. The function and anatomy of the central macula is preserved until late in the disease process.
  • Peripheral visual field loss. Peripheral visual field loss manifests as a ring scotoma and generally follows changes in the fundus appearance. Areas of visual field loss closely match areas of chorioretinal degeneration.
  • The electroretinogram (ERG) of affected males may at first show a pattern of rod-cone degeneration, which eventually becomes non-recordable.
  • Family history consistent with X-linked inheritance

Carrier females

  • Fundus appearance. Carrier females have fundus changes that are similar to those in affected males and follow a similar pattern of progression.
  • No visual complaints. Carrier females do not experience significant visual impairment and in general are asymptomatic.
  • Test results. Carrier females may show changes with ERG, dark adaptation, and visual field testing.
    • The ERG may be normal in obligate carriers or in carriers with characteristic fundus changes. Sieving et al [1986] demonstrated that although abnormal responses may be recorded in female carriers with a dim blue flash, a dark-adapted white flash, or a flickering stimulus, no one test consistently predicted carrier status.
    • Fundus autofluorescence may demonstrate in female carriers patchy areas of loss of fluorescence throughout the fundus [Preising et al 2009].
    • Carrier females age 21-65 years had no change in the Arden ratio of the electrooculogram [Yau et al 2007].

Establishing the Diagnosis

The diagnosis of choroideremia is established in a proband with the identification of a pathogenic variant in CHM (see Table 1).

Molecular testing approaches can include the following.

  • Single-gene testing:
  • Use of a multi-gene panel that includes CHM and other genes of interest (see Differential Diagnosis). Note: The genes included and the methods used in multi-gene panels vary by laboratory and over time.
  • Genomic testing if single gene testing (and/or use of a multi-gene panel) has not confirmed a diagnosis in an individual with features of CHM. Such testing may include whole-exome sequencing (WES) or whole-genome sequencing (WGS).

Notes regarding WES and WGS. (1) False negative rates vary by genomic region; therefore, genomic testing may not be as accurate as targeted single gene testing or multi-gene molecular genetic testing panels; (2) most laboratories confirm positive results using a second, well-established method; (3) nucleotide repeat expansions and epigenetic alterations cannot be detected; (4) deletions/duplications larger than 8-10 nucleotides are not detected effectively [Biesecker & Green 2014].

For individuals with atypical findings (see Genetically Related Disorders), a different testing strategy should be considered.

  • For males presenting with choroideremia in addition to cognitive issues, and/or hearing loss, testing should begin with a chromosomal microarray (CMA) to look for a large contiguous deletion that includes CHM.
  • For symptomatic females in whom a CHM pathogenic variant is not identified, a karyotype may be considered to look for an X:autosome translocation resulting in a disruption of CHM.

Table 1.

Summary of Molecular Genetic Testing Used in Choroideremia

Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method
Affected MalesCarrier Females
CHMSequence analysis 295% 3, 4Unknown 3, 5
Deletion / duplication analysis 6Unknown
Targeted mutation analysis 7Most pathogenic variants in the Finnish population
1.

See Table A. Genes and Databases for chromosome locus and protein name. See Molecular Genetics for information on allelic variants.

2.

Sequence analysis detects variants that are benign, likely benign, of unknown significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exonic or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

3.

van den Hurk et al [1997], Fujiki et al [1999], McTaggart et al [2002], van den Hurk et al [2003], Freund (MSc thesis, University of Alberta, unpublished)

4.

Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exoninc or whole-gene deletion on the X chromosome in affected males; confirmation may require additional testing by deletion/duplication analysis.

5.

Sequence analysis of genomic DNA cannot detect deletion of one or more exons or the entire X-linked gene in a heterozygous female.

6.

Testing that identifies exonic or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

7.

Targeted analysis that detects c.1609+2dupT [Sankila et al 1992] for individuals of Finnish ancestry. Note: Pathogenic variants included in a panel may vary by laboratory.

Test characteristics. Information on test sensitivity and specificity as well as other test characteristics can be found at EuroGentest [Moosajee et al 2014] (full text).

Clinical Description

Natural History

Affected males. Choroideremia (CHM) is characterized by progressive chorioretinal degeneration in affected males. Typically, symptoms evolve from night blindness to peripheral visual field loss, with central vision preserved until late in life. Males in their 40s have very good visual acuity but only a small visual field. Later, around age 50-70 years, the central vision is lost.

A study of 115 males with CHM confirmed the typically slow rate of visual acuity loss and the generally good prognosis for central visual acuity retention until the seventh decade [Roberts et al 2002]. In that study, 84% of males under age 60 years had visual acuity of 20/40 or better and 35% of individuals over age 60 years had a visual acuity of 20/200 or worse.

Posterior subcapsular cataracts are found in 31% of males.

Cystoid macular edema (CME) has been identified in patients with choroideremia. Genead & Fishman [2011] reviewed 16 patients without lesions by fundus examination; ten patients (62.5%) showed a degree of CME on spectral-domain optical coherence tomography.

Carrier females. Carrier females are generally asymptomatic; however, signs of chorioretinal degeneration can be observed with careful fundus examination. These signs become more readily apparent after the second decade. Night blindness and field loss can also develop later in life due to expanding areas of choroioretinal atrophy in females (see Clinical Utility Gene Card) [Moosajee et al 2014]. Females who demonstrate clinical findings that mimic those of affected males likely have skewed X-chromosome inactivation.Symptomatic but mildly affected females are likely underreported in the literature.

Genotype-Phenotype Correlations

Genotype-phenotype correlations have not yet been demonstrated for this disorder.

Nomenclature

Choroideremia, the only diagnostic term used for this condition, has consistently been applied for more than 130 years.

Prevalence

Prevalence is estimated at 1:50,000.

Differential Diagnosis

Laboratory analysis may not always support the clinical diagnosis of choroideremia (CHM). For instance, a study identified 13 individuals who had a clinical diagnosis of CHM without a lab test confirmation [Lee et al 2003]. On reassessment of available clinical data, alternate diagnoses were suggested for eight of the 13 patients. Specifically, CHM needs to be distinguished from the following retinal dystrophies:

  • Retinitis pigmentosa (RP) is a group of inherited disorders in which abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina lead to progressive visual loss. The symptoms of RP (i.e., "night blindness" and constriction of peripheral visual field) are similar to those of CHM. In the later stages of CHM, when the loss of choroid and retina are significant, the fundus appearance may be confused with end-stage RP; however, the degree of migration of pigment into the retina that typifies RP is not seen in individuals with CHM. Diagnosis of RP relies on electroretinography (ERG) and visual field testing. RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Pathogenic variants in RPGR and RP2 are the most common causes of X-linked RP, accounting for 70%-90% and 10%-20%, respectively, of X-linked RP. The pattern of autofluorescence retinal imaging in carriers of X-linked RP is distinct from that of CHM carriers [Preising et al 2009].
  • Usher syndrome type 1 is characterized by congenital, bilateral, profound hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. Unless fitted with a cochlear implant, individuals do not typically develop speech. Retinitis pigmentosa develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity. The diagnosis is established on clinical grounds using electrophysiologic and subjective tests of hearing and retinal function. Usher syndrome type 1 may be confused with the contiguous gene deletion syndrome, CHM and deafness with perilymphatic gusher. The scalloped areas of significant chorioretinal degeneration with preservation of the choroidal vessels, typical of CHM, are not seen in Usher syndrome type 1. Usher syndrome type I is inherited in an autosomal recessive manner. Mutation of genes at a minimum of nine different loci causes Usher syndrome type I. Genes at six of these loci – MYO7A (USH1B), USH1C, CDH23 (USH1D), PCDH15 (USH1F), USH1G, and CIB2 (USH1J) – have been identified.
  • Gyrate atrophy of choroid and retina (OMIM 258870). The progressive nature of scalloped areas of chorioretinal atrophy seen in gyrate atrophy of the choroid and retina may be confused with CHM. Gyrate atrophy of the choroid and retina is an autosomal recessive condition caused by pathogenic variants in the gene encoding ornithine aminotransferase. Individuals with gyrate atrophy of the choroid and retina have elevated plasma concentration of ornithine, which is not seen in individuals with CHM.

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to SimulConsult®, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with choroideremia (CHM), the following evaluations are recommended:

  • Ophthalmologic examination including visual acuity and Goldmann visual field testing for a baseline
  • Electroretinogram
  • Funduscopic examination
  • Optical coherence tomography (OCT)
  • Medical genetics consultation

Treatment of Manifestations

Retinal detachment which may occur more commonly in patients with high myopia (as seen in CHM) is treated by conventional surgical techniques by an ophthalmologist.

Cataract surgery may be required for individuals with a posterior subcapsular cataract.

UV-blocking sunglasses may have a protective role when an affected individual is outdoors.

Low vision services are designed to benefit those whose ability to function is compromised by vision impairment. Low vision specialists, often optometrists, help optimize the use of remaining vision. Services provided vary based on age and needs.

Counseling from organizations or professionals who work with the blind and visually impaired may be needed to help the affected individual cope with issues such as depression, loss of independence, fitness for driving, and anxiety over job loss.

Nutrition and ocular health have become increasingly topical:

  • For those individuals who do not have access to fresh fruit and leafy green vegetables, a supplement with antioxidant vitamins may be important.
  • No information is available on the effectiveness of vitamin A supplementation in the treatment of CHM.
  • A source of omega-3 very-long-chain fatty acids, including docosahexaenoic acid, may be beneficial, as clinical studies suggest that a regular intake of fish is important.

Prevention of Secondary Complications

Rare cases of choroidal neovascularization may be treated with intravitreal bevacizumab [Palejwala et al 2014]

Surveillance

Regular ophthalmologic examination to monitor progression of CHM is recommended as affected individuals need advice regarding their levels of visual function. Goldmann visual field examinations provide practical information for both the clinician and the affected individual.

Spectral domain-OCT (SD-OCT) is useful during therapeutic trials to measure macular thickness and the presence of cystoid macular edema [Genead & Fishman 2011].

Agents/Circumstances to Avoid

UV exposure from sunlight reflected from water and snow should be avoided.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Gene therapy for individuals with CHM has been considered an achievable goal. Introduction of adenovirus containing the CHM coding region can restore in vitro protein levels and REP-1 activity in CHM-deficient lymphocytes and fibroblasts [Anand et al 2003].

Vasireddy et al [2013] reported encouraging preclinical results using induced pluripotent stem cells from patients with CHM as in vitro models as well as normal-sighted mice as in vivo models. Delivery of CHM cDNA via a recombinant adeno-associated viral vector (AAV2) did not induce cytotoxicity in either model, suggesting that a human clinical trial for this condition is possible. To date, a safety trial of AAV2-mediated gene therapy in human subjects with CHM has been completed [MacLaren et al 2014]. Despite the requirement for submacular placement of the vector through microsurgical techniques, no serious adverse events were noted.

Morgan et al [2014] provided supporting evidence that the retinal pigment epithelium and photoreceptor layers should be the primary targets for experimental therapies based on their high resolution retinal imaging studies.

Other preclinical studies suggest that AAV8 may also be a candidate vector for choroideremia human gene therapy trials [Black et al 2014].

Note: Gene therapy trials for CHM are currently planned or underway and are registered with www.clinicaltrials.gov.

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Other

Genead et al [2012] studied the use of 2% topical dorzolamide ophthalmic solution to treat two CHM patients with cystoids macular edema. Clear improvements in retinal thickness were identified though changes to visual acuity, retinal sensitivity and other functional measures were not clinically significant.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Choroideremia (CHM) is inherited in an X-linked manner.

Risk to Family Members

Parents of a proband

  • The father of an affected male will not have CHM nor will he be a carrier of the CHM pathogenic variant.
  • In a family with more than one affected male, the mother of an affected male is an obligate carrier.
  • If pedigree analysis reveals that the proband is the only affected family member, it is appropriate to examine the retina of the mother through a dilated pupil to determine if she has evidence of carrier status.
  • Possible genetic explanations for a male proband with no family history of CHM (i.e., a simplex case) are:
    • The proband has a de novo mutation. In this instance, the proband's mother does not have a germline mutation and does not have the retinal changes seen in carriers. The only other family members at risk are the offspring of the proband.
    • The proband's mother has a de novo gene mutation and may or may not have the retinal changes seen in carriers. One of two types of de novo gene mutations may be present in the mother:
      a.

      A germline mutation that was present at the time of her conception, is present in every cell of her body, and is detectable in her DNA;
      OR

      b.

      A pathogenic variant that is present only in her ovaries (termed "germline mosaicism") and is not detectable in the DNA from her leukocytes.

  • Germline mosaicism has not been reported in individuals with CHM but it has been observed in many X-linked disorders and should be considered in the genetic counseling of at-risk family members. In both instances a) and b), each offspring of the proband's mother is at risk of inheriting the pathogenic variant; none of the sibs of the proband's mother, however, is at risk of having inherited the altered gene.

Sibs of a proband

  • The risk to the sibs of a proband depends on the genetic status of the mother.
  • If the mother has the pathogenic variant, the chance of transmitting the CHM pathogenic variant in each pregnancy is 50%. Male sibs who inherit the pathogenic variant will be affected; female sibs who inherit the pathogenic variant will be carriers and will usually not be affected.
  • When the mother has a normal fundus examination, the risk to the sibs of a proband appears to be low. Although no instances of germline mosaicism have been reported, it remains a possibility.

Offspring of a male proband. Affected males transmit the pathogenic variant to all of their female offspring and none of their male offspring.

Family members of a proband. If a parent of the proband also has a pathogenic variant, his or her female family members may be at risk of being carriers (asymptomatic or symptomatic) and his or her male family members may be at risk of being affected, depending on their genetic relationship to the proband.

Carrier Detection

Carrier testing of at-risk female relatives is possible if the CHM pathogenic variant has been identified in the family.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

Specific risk issues. It is not possible to predict at what age an affected male will start to experience vision problems and how quickly the disease will progress. It is also not possible to know if a carrier female will manifest any vision loss. At one time, consensus held that carrier females experienced only mild vision disturbances later in life; however, manifesting carriers may have vision loss similar to that of affected males because of skewed X-chromosome inactivation.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the CHM pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at increased risk may be available from a clinical laboratory that offers either testing of this gene or custom prenatal testing.

Requests for prenatal testing for conditions which (like CHM) do not affect intellect are not common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the CHM pathogenic variant has been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Choroideremia Research Foundation
    23 East Brundreth Street
    Springfield MA 01109-2110
    Phone: 413-781-2274
  • Foundation Fighting Blindness
    11435 Cronhill Drive
    Owings Mill MD 21117-2220
    Phone: 800-683-5555 (toll-free); 800-683-5551 (Toll-free TDD); 410-568-0150; 410-363-7139 (local TDD)
    Email: info@FightBlindness.org
  • National Library of Medicine Genetics Home Reference
  • National Eye Institute
    31 Center Drive
    MSC 2510
    Bethesda MD 20892-2510
    Phone: 301-496-5248
    Email: 2020@nei.nih.gov
  • eyeGENE® - National Ophthalmic Disease Genotyping Network Registry
    Phone: 301-435-3032
    Email: eyeGENEinfo@nei.nih.gov

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Choroideremia: Genes and Databases

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

OMIM Entries for Choroideremia (View All in OMIM)

300390CHM GENE; CHM
303100CHOROIDEREMIA; CHM

Gene structure. The gene comprises 15 exons. For a detailed summary of gene and protein information, see Table A, Gene Symbol.

Pathogenic allelic variants. Nearly all known CHM pathogenic variants are nonsense mutations, small deletions or insertions, or splice site alterations that predict or result in truncation of the protein product (REP-1).

An exception is the report of a pathogenic L1 retrotransposon insertion in exon 6 that results in the direct splicing of exon 5 to exon 7 with maintenance of the reading frame. The missing amino acids are part of a conserved region that forms a hydrophobic groove that is proposed to bind geranyl-geranyl groups [van den Hurk et al 2003].

Few missense variants have been reported.

Table 2.

CHM Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide ChangeProtein Amino Acid ChangeReference Sequences
c.1609+2dupTSee footnote 1NM_000390​.2
NP_000381​.1

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

Splice site mutation

Normal gene product. Rab escort protein-1 (REP-1) is a component of Rab geranylgeranyltransferase, an enzyme complex that mediates correct intracellular vesicular transport.

The REP-1 protein functions in the prenylation (covalent addition of 20-carbon geranylgeranyl units) to Rab GTPases. Lymphocytes from individuals with CHM show marked inability to prenylate Rab proteins, in particular Rab27A. Rab proteins have a role in organelle formation and trafficking of vesicles in exocytic and endocytic pathways [Seabra et al 2002]. In an individual with choroideremia, REP-2, encoded by CHML and functionally similar to REP-1, may compensate for the loss of REP-1 function in all non-retinal cells [Cremers et al 1994].

Abnormal gene product. Most often the pathogenic variant predicts or results in a truncated product that is degraded based on absence of immunohistochemical staining of REP-1 protein in cells from peripheral tissues of individuals with CHM [MacDonald et al 1998]. In silico analyses on the effect of a novel missense and other mutations on 3D structure of REP-1 have been reported [Sergeev et al 2009].

References

Published Guidelines/Consensus Statements

  1. American Academy of Ophthalmology Task Force on Genetic Testing. Recommendations for genetic testing of inherited eye diseases – 2014. Available online. 2014. Accessed 2-25-15.

Literature Cited

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  2. Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;371:1170. [PubMed: 25229935]
  3. Black A, Vasireddy V, Chung DC, Maguire AM, Gaddameedi R, Tolmachova T, Seabra M, Bennett J. Adeno-associated virus 8-mediated gene therapy for choroideremia: preclinical studies in in vitro and in vivo models. J Gene Med. 2014;16:122–30. [PubMed: 24962736]
  4. Cremers FP, Armstrong SA, Seabra MC, Brown MS, Goldstein JL. REP-2, a Rab escort protein encoded by the choroideremia-like gene. J Biol Chem. 1994;269:2111–7. [PubMed: 8294464]
  5. Fujiki K, Hotta Y, Hayakawa M, Saito A, Mashima Y, Mori M, Yoshii M, Murakami A, Matsumoto M, Hayasaka S, Tagami N, Isashiki Y, Ohba N, Kanai A. REP-1 gene mutations in Japanese patients with choroideremia. Graefes Arch Clin Exp Ophthalmol. 1999;237:735–40. [PubMed: 10447648]
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  21. Sergeev YV, Smaoui N, Sui R, Stiles D, Gordiyenko N, Strunnikova N, Macdonald IM. The functional effect of pathogenic mutations in Rab escort protein 1. Mutat Res. 2009 Jun 1;665(1-2):44–50. [PMC free article: PMC2680797] [PubMed: 19427510]
  22. Sieving PA, Niffenegger JH, Berson EL. Electroretinographic findings in selected pedigrees with choroideremia. Am J Ophthalmol. 1986;101:361–7. [PubMed: 3953730]
  23. van den Hurk JA, Schwartz M, van Bokhoven H, van de Pol TJ, Bogerd L, Pinckers AJ, Bleeker-Wagemakers EM, Pawlowitzki IH, Ruther K, Ropers HH, Cremers FP. Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene. Hum Mutat. 1997;9:110–7. [PubMed: 9067750]
  24. van den Hurk JA, van de Pol DJ, Wissinger B, van Driel MA, Hoefsloot LH, de Wijs IJ, van den Born LI, Heckenlively JR, Brunner HG, Zrenner E, Ropers HH, Cremers FP. Novel types of mutation in the choroideremia (CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon. Hum Genet. 2003;113:268–75. [PubMed: 12827496]
  25. Vasireddy V, Mills JA, Gaddameedi R, Basner-Tschakarjan E, Kohnke M, Black AD, Alexandrov K, Zhou S, Maguire AM, Chung DC, Mac H, Sullivan L, Gadue P, Bennicelli JL, French DL, Bennett J. AAV-mediated gene therapy for choroideremia: preclinical studies in personalized models. PLoS One. 2013;8:e61396. [PMC free article: PMC3646845] [PubMed: 23667438]
  26. Yau RJ, Sereda CA, McTaggart KE, Sauve Y, MacDonald IM. Choroideremia carriers maintain a normal electro-oculogram (EOG). Doc Ophthalmol. 2007;114:147–51. [PubMed: 17333094]
  27. Yntema HG, van den Helm B, Kissing J, van Duijnhoven G, Poppelaars F, Chelly J, Moraine C, Fryns JP, Hamel BC, Heilbronner H, Pander HJ, Brunner HG, Ropers HH, Cremers FP, van Bokhoven H. A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. Genomics. 1999;62:332–43. [PubMed: 10644430]

Suggested Reading

  1. MacDonald IM, Russell L, Chan CC. Choroideremia: new findings from ocular pathology and review of recent literature. Surv Ophthalmol. 2009;54:401–7. [PMC free article: PMC2679958] [PubMed: 19422966]
  2. Sandberg MA, Gaudio AR. Reading speed of patients with advanced retinitis pigmentosa or choroideremia. Retina. 2006;26:80–8. [PubMed: 16395143]
  3. Cremers FPM, Ropers HH. Choroideremia. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). New York, NY: McGraw-Hill. Chap 236. 2015.

Chapter Notes

Author History

Stephanie Chan, MSc, CGC, CCGC (2015-present)
Stacey Hume, PhD (2015-present)
Ian M MacDonald, MD, CM (2003-present)
Kerry McTaggart, MSc; University of Alberta (2003-2007)
Meira R Meltzer, MA, MS, CGC; National Eye Institute (2007-2010)
Miguel C Seabra, MD, PhD (2003-present)
Christina Sereda, MSc; University of Alberta (2003-2007)
Nizar Smaoui, MD; GeneDx (2007-2015)

Revision History

  • 26 February 2015 (me) Comprehensive update posted live
  • 3 June 2010 (me) Comprehensive update posted live
  • 28 May 2008 (cd) Revision: duplication/deletion analysis available clinically
  • 3 May 2007 (me) Comprehensive update posted to live Web site
  • 29 December 2004 (me) Comprehensive update posted to live Web site
  • 2 January 2004 (im) Revision: testing
  • 7 May 2003 (im) Revision: Molecular genetic testing; prenatal diagnosis
  • 21 February 2003 (me) Review posted to live Web site
  • 2 December 2002 (im) Original submission
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