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X-Linked Juvenile Retinoschisis

Synonyms: Juvenile Retinoschisis, X-Linked Retinoschisis

, MD, PhD, , MD, CM, , MA, MS, and , MD, FACMG.

Author Information
, MD, PhD
Director, National Eye Institute
National Institutes of Health
Bethesda, Maryland
, MD, CM
Chair, Department of Ophthalmology
University of Alberta
Royal Alexandra Hospital
Edmonton, Alberta, Canada
, MA, MS
National Eye Institute
National Institutes of Health
Bethesda, Maryland
, MD, FACMG
Director, Division of Inherited Eye Disease
GeneDx
Gaithersburg, Maryland

Initial Posting: ; Last Update: May 12, 2009.

Summary

Disease characteristics. X-linked juvenile retinoschisis is characterized by symmetric bilateral macular involvement with onset in the first decade of life, in some cases as early as age three months. Fundus examination shows areas of schisis (splitting of the nerve fiber layer of the retina) in the macula, sometimes giving the impression of a spoke wheel pattern. Schisis of the peripheral retina, predominantly inferotemporally, occurs in approximately 50% of individuals. Affected males typically have vision of 20/60 to 20/120. Visual acuity often deteriorates during the first and second decades of life but then remains relatively stable until the fifth or sixth decade.

Diagnosis/testing. The diagnosis of X-linked juvenile retinoschisis is based on fundus findings, results of electrophysiologic testing, and molecular genetic testing. RS1 is the only gene known to be associated with X-linked juvenile retinoschisis.

Management. Treatment of manifestations: low vision aids such as large-print textbooks; preferential seating in the front of the classroom; and use of handouts with high contrast. Surgery may be required to address the infrequent complications of vitreous hemorrhage and full-thickness retinal detachment. Surveillance: annual evaluation of children under age ten years by a pediatric ophthalmologist or retina specialist. Agents/circumstances to avoid: head trauma and high-contact sports to reduce risk of retinal detachment and vitreous hemorrhage.

Genetic counseling. X-linked juvenile retinoschisis is inherited in an X-linked manner. Carrier women have a 50% chance of transmitting the disease-causing mutation in each pregnancy: males who inherit the mutation will be affected; females who inherit the mutation will be carriers and will nearly always have normal visual function and electrophysiology. Affected males pass the disease-causing mutation to all of their daughters and none of their sons. Carrier testing for at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.

Diagnosis

Clinical Diagnosis

Affected males. The diagnosis of X-linked juvenile retinoschisis is made in a young male with the following findings:

  • Reduced visual acuity, typically between 20/60 and 20/120
  • The following findings on fundus examination:
    • Areas of schisis (splitting of the nerve fiber layer of the retina) in the macula, sometimes giving the impression of a spoke wheel pattern (Figure 1).
    • Schisis of the peripheral retina, predominantly inferotemporally, in approximately 50% of individuals [Eksandh et al 2000]. The associated elevation of the surface layer of the retina into the vitreous has been described as "vitreous veils" (Figure 2).
    • On occasion, more severe involvement of the macula (Figure 3)
    • On occasion, the Mizuo phenomenon, a color change in the retina after dark adaptation with the onset of light
  • Electroretinogram (ERG) showing selective reduction of the amplitude of the dark-adapted b-wave amplitude but relative preservation of the a-wave amplitude [Nakamura et al 2001]

    Note: Because an individual with X-linked juvenile retinoschisis with an identified RS1 mutation has had a technically normal ERG in which the b-wave was still present [Sieving et al 1999a], the diagnosis of X-linked juvenile retinoschisis cannot be excluded based on a normal ERG, although this occurrence is extremely rare.
  • A family history consistent with X-linked inheritance
Figure 1

Figure

Figure 1. Fundus photo of a male with juvenile retinoschisis. Arrow points to typical spoke-wheel pattern of foveal cysts.

Figure 2

Figure

Figure 2. Fundus photo of the peripheral retina of a male with juvenile retinoschisis. Area marked with arrows shows a partial-thickness retinal hole.

Figure 3

Figure

Figure 3. Fundus photo of a male with juvenile retinoschisis showing atypical, more severe findings with arrows pointing to atrophic macular changes

Carrier females. In most cases, carrier females cannot be identified by clinical examination. Carrier females nearly always have normal visual function and a normal ERG. Rarely, examination of the peripheral retina may show white flecks or areas of schisis.

Testing

Intravenous fluorescein angiogram appears normal in younger individuals, whereas older individuals may have atrophic changes in the retinal pigment epithelium (RPE).

Optical coherence tomography (OCT) shows small cystic-appearing spaces in the perifoveal region and larger cystic-like spaces within the fovea in most school-age individuals [Apushkin et al 2005]. Cystic spaces are not as evident after adolescence. OCT scans of older individuals may appear normal because of flattening of cysts with age.

Molecular Genetic Testing

Gene. RS1 is the only gene in which mutation is known to cause X-linked juvenile retinoschisis.

Clinical testing

Table 1. Summary of Molecular Genetic Testing Used in X-Linked Juvenile Retinoschisis

Gene SymbolTest MethodMutations DetectedMutation Detection Frequency by Test Method 1
Affected MalesCarrier Females 2
RS1Targeted mutation analysisp.Glu72Lys, p.Gly74Val, p.Gly109Arg~95% 3
Sequence analysisSequence variants~90%90%
Partial- and whole-gene deletion6% 40% 5
Deletion / duplication testing 6Partial- and whole-gene deletions~6%~6%

2. When no affected males in the family are available for testing

3. In persons of Finnish heritage

4. Gel sizing analysis can detect putative exonic, multiexonic, and whole-gene deletions in RS1 in affected males because of lack of amplification by PCR.

5. Sequence analysis of genomic DNA cannot detect deletion of one or more exons in RS1 in females.

6. Testing that detects deletions/duplications not readily detectable by sequence analysis of genomic DNA; a variety of methods including quantitative PCR, or array GH may be used.

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

Confirming the diagnosis in a proband. In general, the diagnosis in a proband can be made by ophthalmologic examination and confirmed by electroretinogram.

To identify the mutation in an affected male:

1.

In males of Finnish heritage, perform targeted mutation analysis of the four common mutations.

2.

If the mutation is not identified, and for males of non-Finnish heritage, perform sequence analysis.

3.

In males in whom a mutation is not identified by sequence analysis, consider deletion testing.

Carrier testing for at-risk female relatives. (1) Carriers are heterozygotes for this X-linked disorder and rarely develop clinical findings related to the disorder. (2) Identification of female carriers requires either (a) prior identification of the disease-causing mutation in the family or, (b) if an affected male is not available for testing, molecular genetic testing first by sequence analysis, and then, if no mutation is identified, by deletion/duplication test methods to detect gross structural abnormalities.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Clinical Description

Natural History

X-linked juvenile retinoschisis is a symmetric bilateral macular disorder with onset in the first decade of life, in some cases as early as age three months. Affected males generally present with reduction in vision by early grade school. Affected males typically have vision of 20/60 to 20/120 on first presentation.

Visual acuity may deteriorate during the first and second decades of life but then remain relatively stable, with only very slowly progressive reduction from macular atrophy, until the fifth or sixth decade [Eksandh et al 2000, Apushkin et al 2005]. Visual loss may progress to legal blindness (acuity <20/200) by the sixth or seventh decade. In individuals over age 50 years, macular pigmentary changes and some degree of atrophy of the RPE are common.

Variation in disease presentation and disease progression is observed even among members of the same family.

Appearance of foveal lesions varies from largely radial striations (3%), microcystic lesions (34%), honeycomb-like cysts (8%), or their combinations (31%) to non-cystic-appearing foveal changes including pigment mottling (8%), loss of the foveal reflex (8%), or an atrophic-appearing lesion (8%) [Apushkin et al 2005].

X-linked juvenile retinoschisis progresses to retinal detachment in an estimated 5% to 22% of affected individuals. Retinal detachment can occur in infants with severe retinoschisis. About 4% to 40% of individuals with X-linked juvenile retinoschisis develop vitreous hemorrhage.

Genotype-Phenotype Correlations

No genotype-phenotype correlations have been identified [Sieving et al 1999b, Eksandh et al 2000, Inoue et al 2000].

Missense, splice site, frameshift, insertion, and deletion mutations all result in the same phenotype. Some studies suggest that mutations that putatively cause protein truncation result in greater clinical severity [Sieving et al 1999b].

Penetrance

X-linked juvenile retinoschisis exhibits complete penetrance with variable expressivity.

Nomenclature

Other terms correctly used in the past to refer to X-linked juvenile retinoschisis:

  • Juvenile retinoschisis
  • Congenital retinoschisis
  • Juvenile macular degeneration/dystrophy

Other terms incorrectly used in the past to refer to X-linked juvenile retinoschisis:

  • Cone dystrophy
  • Macular hole

Prevalence

Estimates of the prevalence of X-linked juvenile retinoschisis vary from one in 5,000 to one in 25,000 [The Retinoschisis Consortium 1998].

Differential Diagnosis

While the presence of retinoschisis in an individual with a positive family history of X-linked juvenile retinoschisis establishes the diagnosis in that person, making the diagnosis in a male with no known family history may be more difficult.

Cystoid macular edema may mimic foveal retinoschisis. Macular edema may be caused by diabetes mellitus, inflammatory conditions of the eye (uveitis), or intraocular surgery.

Amblyopia can be a referring diagnosis when foveal schisis changes are subtle. Suspicion of X-linked juvenile retinoschisis is raised if family history indicates other affected males in an X-linked inheritance pattern.

Goldmann-Favre vitreoretinal degeneration and enhanced S-cone syndrome, caused by mutations in NR2E3, may mimic X-linked juvenile retinoschisis. Onset occurs in infancy. Generally, affected individuals have severely impaired vision including marked visual field loss and severe night blindness. Coarse intraretinal cysts may be seen with peripheral retinoschisis; no vitreous veils are observed. The electroretinogram shows markedly reduced a-waves and b-waves with altered timing rather than simply the reduction in the b-wave amplitude found in X-linked juvenile retinoschisis. Inheritance is autosomal recessive.

Retinitis pigmentosa (RP) is the referring diagnosis in many persons with X-linked juvenile retinoschisis. Characteristics of RP that distinguish it from X-linked juvenile retinoschisis include some or all of the following: optic nerve gliotic pallor, narrowing of retinal vessels, and intraretinal pigment dispersion or clumping. The X-linked form of RP may cause confusion with X-linked juvenile retinoschisis, and other family members should be examined; the ERG in RP (particularly X-linked RP) is markedly diminished rather than having the selective reduction in b-wave amplitude seen in X-linked juvenile retinoschisis. Noble et al [1978] reported a family with rod-cone dystrophy and associated foveal schisis. For this reason, foveal retinoschisis alone does not make the diagnosis of X-linked juvenile retinoschisis.

VCAN-related vitreoretinopathy, which includes Wagner syndrome and erosive vitreoretinopathy (ERVR), is characterized by reduced visual acuity and night blindness of variable degree, mild or occasionally moderate-to-severe myopia, presenile cataract, “optically-empty vitreous” on slit-lamp examination and avascular vitreous strands and veils, progressive chorioretinal atrophy, and retinal detachment at advanced stages of the disease. The first signs usually become apparent during early adolescence but onset can be as early as age two years. Mutations in VCAN (previously CSPG2) are causative. Inheritance is autosomal dominant.

Degenerative retinoschisis is an idiopathic, degenerative disease of the peripheral retina. No evidence suggests genetic etiology [Lewis 2003]. In degenerative or age-related peripheral retinoschisis, splitting occurs in the outer retina through the outer nuclear layer and plexiform layer, whereas in X-linked juvenile retinoschisis, splitting is found in the nerve fiber layer and the ganglion cell layer [Sieving 1998].

Retinal detachment, in which the full-thickness retina elevates and lifts off from the underlying ocular support, differs from retinoschisis, in which the retina splits through the nerve fiber layer. Retinal detachment in an otherwise normal eye can be surgically repaired, whereas retinal detachment associated with retinoschisis usually cannot.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with X-linked juvenile retinoschisis, the following evaluations are recommended:

  • Visual acuity
  • Goldmann visual field
  • Family history
  • Electroretinogram
  • Funduscopic examination
  • Optical coherence tomography

Treatment of Manifestations

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.

Public school systems are mandated by federal law to provide appropriate education for children who have vision impairment. Assistance may include larger print textbooks, preferential seating in the front of the classroom, and use of handouts with higher contrast.

Many individuals with X-linked juvenile retinoschisis are able to obtain a restricted driver's license. Some individuals have found specially designed telescopic lenses useful when driving; legal use of telescopic lenses may vary by locale.

Retinoschisis affects primarily the inner retinal layers; hence, retinoschisis alone (without retinal detachment) is at best difficult to treat surgically.

Treatment of retinoschisis may require the care of a retinal surgeon to address the infrequent complications of vitreous hemorrhage and full-thickness retinal detachment. The clinical presentation of a large area of peripheral retinoschisis may mask a true retinal detachment. Advice from an ophthalmologist or retinal surgeon should be sought when in doubt.

Surveillance

Annual evaluation of children under age ten years by a pediatric ophthalmologist or retina specialist is recommended.

Older children and adults need less frequent monitoring.

Agents/Circumstances to Avoid

Although retinal detachment and vitreous hemorrhage occur in a minority of affected individuals (5%-22% and 4%-40%, respectively), general avoidance of head trauma and high-contact sports is recommended.

Evaluation of Relatives at Risk

At-risk male relatives of a proband should be examined by an ophthalmologist to confirm affected or non-affected status for early treatment of retinal detachment.

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

Therapies Under Investigation

A mouse model of human X-linked juvenile retinoschisis is being studied to determine whether supplementation with functional normal retinoschisin protein can produce improvement in ERG function and retina morphology [Zeng et al 2004, Min et al 2005]. Current evaluation of the mouse model confirms that it appropriately mimics structural features of human X-linked juvenile retinoschisis. Replacements of the deficient protein through use of a neomycin resistance cassette or through use of an AAV vector have both been successful, suggesting that, with additional study, gene therapy may become a viable strategy for therapeutic intervention [Kjellstrom et al 2007].

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

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

X-linked juvenile retinoschisis is inherited in an X-linked recessive manner.

Risk to Family Members

Parents of a proband

Sibs of a proband

  • The risk to sibs depends on the carrier status of the mother.
  • If the mother is a carrier, the chance of transmitting the disease-causing mutation in each pregnancy is 50%. Male sibs who inherit the mutation will be affected; female sibs who inherit the mutation will be carriers. Carriers nearly always have normal visual function and normal electrophysiology (i.e., ERG).
  • If the mother is not a carrier, the risk to sibs is low but may be higher than that of the general population because the risk of germline mosaicism in mothers is not known.

Offspring of a proband. Males will pass the disease-causing mutation to all of their daughters and none of their sons.

Other family members of a proband. The proband's maternal aunts may be at risk of being carriers and the aunt's offspring, depending on their gender, may be at risk of being carriers or of being affected.

Carrier Detection

Carrier testing of at-risk female relatives is possible if the disease-causing mutation in the family is known.

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.

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, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Prenatal testing is possible for pregnancies of women who are carriers if the RS1 mutation has been identified in a family member. The usual procedure is to determine fetal sex by performing chromosome analysis on fetal cells obtained by chorionic villus sampling (usually performed at ~10-12 weeks' gestation) or by amniocentesis (usually performed at ~15-18 weeks' gestation). If the karyotype is 46,XY, DNA from fetal cells can be analyzed for the known disease-causing mutation.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Requests for prenatal testing for conditions such as X-linked juvenile retinoschisis 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 disease-causing mutation 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.

  • Foundation Fighting Blindness
    11435 Cronhill Drive
    Owings Mills MD 21117-2220
    Phone: 800-683-5555 (toll-free); 800-683-5551 (toll-free TDD); 410-568-0150
    Email: info@fightblindness.org
  • Low Vision Gateway
  • Retina International
    Retina Suisse
    Ausstellungsstrasse 36
    Zurich CH-8005
    Switzerland
    Phone: +41 (0) 44 444 1077
    Fax: +41 (0) 44 444 1070
    Email: christina.fasser@retina-international.org
  • 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. X-Linked Juvenile Retinoschisis: 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 X-Linked Juvenile Retinoschisis (View All in OMIM)

300839RETINOSCHISIN; RS1
312700RETINOSCHISIS 1, X-LINKED, JUVENILE; RS1

Molecular Genetic Pathogenesis

For many years, X-linked juvenile retinoschisis has been thought of as a possible defect in the Muller cell, acting as a cellular scaffold within the retinal architecture. Studies on gene expression and immunolocalization of the normal protein, retinoschisin, indicate that it is expressed within the photoreceptors and has a complex interaction within cells of the retina. Retinoschisin is most highly expressed in the inner segments of the photoreceptors in human eye sections [Mooy et al 2002] and other mammals including mice [Molday et al 2001]. The protein was secreted by differentiated retinoblastoma cells (Weri-Rb1) [Grayson et al 2000]. From expression studies, it remains unclear whether the protein product of mutant disease-causing alleles is secreted properly [Wang et al 2002, Wu & Molday 2003].

In studying the mouse model of retinoschisis created by gene knockout, Weber et al [2002] noted disruption of the normal retinal cellular organization and the appearance of schisis-like cavities in the inner retina. The electroretinogram was affected with selective reduction of the ERG b-wave and a severe effect on the cone ERG. Atypical photoreceptor synapses were also observed, implicating a role for retinoschisin in the normal maintenance of the photoreceptor-bipolar synapse.

Normal allelic variants. A comprehensive list of allelic variants (sequence polymorphisms) is maintained through the RetinoschisisDB© of the Retinoschisis Consortium.

Pathologic allelic variants. More than 125 mutations in RS1 have been associated with X-linked juvenile retinoschisis. Most disease-causing mutations occur in the discoidin domain of RS1, exons 4-6. An up-to-date listing of these mutations may be found by consulting the RetinoschisisDB© of the Retinoschisis Consortium.

Normal gene product. Retinoschisin is a 224-amino acid protein. Retinoschisin is an extracellular protein that exists as a novel disulfide-linked octamer. While it is expected to play a crucial role in cellular organization of the retina, the function of retinoschisin is as yet unknown [Wu et al 2005].

Abnormal gene product. The abnormal gene product may be sequestered in the cell and degraded or secreted [Wang et al 2002, Wu & Molday 2003].

References

Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page Image PubMed.jpg

Literature Cited

  1. Apushkin MA, Fishman GA, Rajagopalan AS. Fundus findings and longitudinal study of visual acuity loss in patients with X-linked retinoschisis. Retina. 2005;25:612–8. [PubMed: 16077359]
  2. Eksandh LC, Ponjavic V, Ayyagari R, Bingham EL, Hiriyanna KT, Andreasson S, Ehinger B, Sieving PA. Phenotypic expression of juvenile X-linked retinoschisis in Swedish families with different mutations in the XLRS1 gene. Arch Ophthalmol. 2000;118:1098–104. [PubMed: 10922205]
  3. Gehrig A, Weber BH, Lorenz B, Andrassi M. First molecular evidence for a de novo mutation in RS1 (XLRS1) associated with X linked juvenile retinoschisis. J Med Genet. 1999;36:932–4. [PMC free article: PMC1734280] [PubMed: 10636740]
  4. Grayson C, Reid SN, Ellis JA, Rutherford A, Sowden JC, Yates JR, Farber DB, Trump D. Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells. Hum Mol Genet. 2000;9:1873–9. [PubMed: 10915776]
  5. Huopaniemi L, Rantala A, Forsius H, Somer M, de la Chapelle A, Alitalo T. Three widespread founder mutations contribute to high incidence of X-linked juvenile retinoschisis in Finland. Eur J Hum Genet. 1999;7:368–76. [PubMed: 10234514]
  6. Inoue Y, Yamamoto S, Okada M, Tsujikawa M, Inoue T, Okada AA, Kusaka S, Saito Y, Wakabayashi K, Miyake Y, Fujikado T, Tano Y. X-linked retinoschisis with point mutations in the XLRS1 gene. Arch Ophthalmol. 2000;118:93–6. [PubMed: 10636421]
  7. Kjellstrom S, Bush RA, Zeng Y, Takada Y, Sieving PA. Retinoschisin gene therapy and natural history in the Rs1h-KO mouse: long-term rescue from retinal degeneration. Invest Ophthalmol Vis Sci. 2007;48:3837–45. [PubMed: 17652759]
  8. Lewis H. Peripheral retinal degenerations and the risk of retinal detachment. Am J Ophthalmol. 2003;136:155–60. [PubMed: 12834683]
  9. Min SH, Molday LL, Seeliger MW, Dinculescu A, Timmers AM, Janssen A, Tonagel F, Tanimoto N, Weber BH, Molday RS, Hauswirth WW. Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis. Mol Ther. 2005;12:644–51. [PubMed: 16027044]
  10. Molday LL, Hicks D, Sauer CG, Weber BH, Molday RS. Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells. Invest Ophthalmol Vis Sci. 2001;42:816–25. [PubMed: 11222545]
  11. Mooy CM, Van Den Born LI, Baarsma S, Paridaens DA, Kraaijenbrink T, Bergen A, Weber BH. Hereditary X-linked juvenile retinoschisis: a review of the role of Müller cells. Arch Ophthalmol. 2002;120:979–84. [PubMed: 12096974]
  12. Nakamura M, Ito S, Terasaki H, Miyake Y. Japanese X-linked juvenile retinoschisis: conflict of phenotype and genotype with novel mutations in the XLRS1 gene. Arch Ophthalmol. 2001;119:1553–4. [PubMed: 11594966]
  13. Noble KG, Carr RE, Siegel IM. Familial foveal retinoschisis associated with a rod-cone dystrophy. Am J Ophthalmol. 1978;85:551–7. [PubMed: 306756]
  14. Sieving PA. Juvenile retinoschisis. In: Traboulsi EI, ed. Genetic Disease of the Eye. New York, NY: Oxford University Press; 1998:347-55.
  15. Sieving PA, Bingham EL, Kemp J, Richards J, Hiriyanna K. Juvenile X-linked retinoschisis from XLRS1 Arg213Trp mutation with preservation of the electroretinogram scotopic b-wave. Am J Ophthalmol. 1999a;128:179–84. [PubMed: 10458173]
  16. Sieving PA, Yashar BM, Ayyagari R. Juvenile retinoschisis: a model for molecular diagnostic testing of X-linked ophthalmic disease. Trans Am Ophthalmol Soc. 1999b;97:451–64. [PMC free article: PMC1298274] [PubMed: 10703138]
  17. The Retinoschisis Consortium; Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis. Hum Mol Genet. 1998;7:1185–92. [PubMed: 9618178]
  18. Wang T, Waters CT, Rothman AM, Jakins TJ, Römisch K, Trump D. Intracellular retention of mutant retinoschisin is the pathological mechanism underlying X-linked retinoschisis. Hum Mol Genet. 2002;11:3097–105. [PubMed: 12417531]
  19. Weber BH, Schrewe H, Molday LL, Gehrig A, White KL, Seeliger MW, Jaissle GB, Friedburg C, Tamm E, Molday RS. Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure. Proc Natl Acad Sci U S A. 2002;99:6222–7. [PMC free article: PMC122930] [PubMed: 11983912]
  20. Wu WW, Molday RS. Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked retinoschisis. J Biol Chem. 2003;278:28139–46. [PubMed: 12746437]
  21. Wu WW, Wong JP, Kast J, Molday RS. RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer. J Biol Chem. 2005;280:10721–30. [PubMed: 15644328]
  22. Zeng Y, Takada Y, Kjellstrom S, Hiriyanna K, Tanikawa A, Wawrousek E, Smaoui N, Caruso R, Bush RA, Sieving PA. RS-1 Gene Delivery to an Adult Rs1h Knockout Mouse Model Restores ERG b-Wave with Reversal of the Electronegative Waveform of X-Linked Retinoschisis. Invest Ophthalmol Vis Sci. 2004;45:3279–85. [PubMed: 15326152]

Chapter Notes

Revision History

  • 12 May 2009 (me) Comprehensive update posted live
  • 18 June 2007 (cd) Revision: MLPA used for carrier testing for female relatives, as current PCR methodologies detect deletions in affected males only
  • 18 January 2006 (me) Comprehensive update posted to live Web site
  • 28 June 2004 (cd) Revision: change in test availability
  • 24 October 2003 (me) Review posted to live Web site
  • 1 July 2003 (ps) Original submission
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    Lewis RA. GeneReviews<sup>®</sup>. 1993
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