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Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

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Bietti Crystalline Dystrophy

Synonyms: Bietti Crystalline Corneoretinal Dystrophy, Bietti Crystalline Retinopathy

, BS, , MS, CGC, , MD, DABMG, FACMG, and , PhD.

Author Information
, BS
Department of Pharmaceutics
University of Washington
Seattle, Washington
, MS, CGC
Genetic Counselor
Banner Health
Glendale, Arizona
, MD, DABMG, FACMG
Ophthalmic Genetics Clinic
Casey Eye Institute
Oregon Health Sciences University
Portland, Oregon
, PhD
School of Pharmacy
University of Washington
Seattle, Washington

Initial Posting: ; Last Revision: June 14, 2012.

Summary

Disease characteristics. Bietti crystalline dystrophy (BCD) is a chorioretinal degeneration characterized by the presence of yellow-white crystals and/or complex lipid deposits in the retina. Progressive atrophy and degeneration of the retinal pigment epithelium (RPE)/choroid lead to symptoms similar to those of other forms of retinal degeneration that fall under the category of retinitis pigmentosa and allied disorders, namely: reduced visual acuity, poor night vision, abnormal retinal electrophysiology, visual field loss, and often impaired color vision. Marked asymmetry between eyes is common. Onset is typically during the second to third decade of life, but ranges from the early teenage years to beyond the third decade. With time, loss of peripheral visual field, central acuity, or both result in legal blindness in most, if not all, affected individuals.

Diagnosis/testing. The diagnosis is based on the finding of numerous small, glistening yellow-white retinal crystals associated with atrophy of the RPE, pigment clumps, and sclerosis of the choroidal vessels; variable crystalline deposits in the corneal limbus; varying degrees of rod and cone dysfunction on electroretinography (ERG); visual field defects; and reflective dots visualized by spectral domain optical coherence tomography (sdOCT). CYP4V2 is the only gene in which mutations are known to cause BCD.

Management. Treatment of manifestations: Referral to low vision specialists and organizations/professionals trained to work with the visually impaired.

Surveillance: Periodic ophthalmologic examination to monitor disease progression and periodic visual field testing particularly as it relates to determination of driving eligibility and eligibility for government programs and/or disability.

Genetic counseling. BCD is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

Diagnosis

Clinical Diagnosis

The diagnosis of Bietti crystalline dystrophy (BCD), a chorioretinal degeneration, is based on the clinical findings of the typical crystalline deposits in the cornea and retina. BCD is one of few ocular diseases for which the diagnosis can be made with a high degree of confidence by careful examination alone. The diagnosis can be confirmed by the finding of disease-associated mutations in CYP4V2.

The following features suggest the diagnosis:

Retina. Numerous small, glistening yellow-white crystals are scattered throughout the posterior pole and sometimes extend to the midperiphery. The crystalline deposits are associated with atrophy of the retinal pigment epithelium (RPE) and choriocapillaris, pigment clumping, and sclerosis of the choroidal vessels.

The crystalline deposits have been observed to diminish or even disappear in areas of severe chorioretinal atrophy, as the disease progresses to later stages [Chen et al 2008, Xiao et al 2011]. Areas in which crystals are still present may represent retina that is still only mildly degenerated or in the progress of degenerating [Kojima et al 2012].

Fluorescein angiography reveals patchy hypofluorescent areas of RPE and choriocapillaris atrophy and a generalized disturbance of the RPE.

Cornea. Crystalline deposits in the corneal limbus have been estimated to occur in one quarter to one third of persons with BCD [Kaiser-Kupfer et al 1994]. It has also been reported that corneal deposits may be more common in persons of northern European background than in Asians [Traboulsi & Faris 1987].

If present, the deposits can usually be seen on slit-lamp examination. However, some crystals may be so fine as to go undetected unless specifically and carefully sought; Takikawa et al [1992] suggest that in some individuals with BCD, corneal crystalline deposits may be too subtle to detect on slit-lamp examination. Spectral microscopy may be more appropriate in such cases.

Electrophysiology. The full-field electroretinogram (ffERG) can show varying degrees of rod and cone dysfunction, ranging from normal to reduced amplitudes of scotopic and photopic responses to undetectable responses [Usui et al 2001]. Thus, electrophysiologic studies are not necessary to establish the diagnosis of BCD; however, they are useful for establishing the magnitude and extent of retinal degeneration.

Although studies have shown that the ffERG responses seem to correlate well with stages of disease severity [Usui et al 2001, Lee et al 2005, Mansour et al 2007], this is not always the case:

  • The ffERG can remain normal even in later stages of the disease. Normal ffERG responses in individuals with BCD with severe atrophy of the RPE and choroid suggest that the neural retina may remain viable despite disruption to retinal lamination [Rossi et al 2011].
  • Regional forms of BCD that may have normal full-field ERGs have been identified [Wilson et al 1989, Weleber & Wilson 1991, Rossi et al 2011]

A multi-focal electroretinogram (mfERG) may detect regional areas of abnormal retinal function when the ffERG is normal, particularly in those regional phenotypes that predominantly affect the posterior pole.

This degree of variation of electrophysiology may be the result of testing at different stages of disease progression. This variability may also reflect variation in loss of function in the gene product, with alleles with residual function associated with greater retention of ffERG amplitudes.

Optical coherence tomography (OCT). Spectral domain OCT (sdOCT) is of value for both diagnosis and management of BCD.

With improved OCT technology, the integrity of retinal structure can be visualized in persons with BCD, including the hyper-reflective dots thought to represent the crystalline deposits. The majority of OCT studies report that the crystalline deposits appear to reside in the RPE-choriocapillaris complex [Pennesi & Weleber 2010, Padhi et al 2011, Kojima et al 2012].

In addition to the crystalline deposits, other reflective spots of various shapes (called retinal tubulation by Zweifel et al [2009]) can be seen by OCT. Kojima et al [2012] reported the presence of spherically shaped, hyper-refractive structures in the outer nuclear layer (ONL) of the retina, particularly located in areas of RPE atrophy. Of note, Kojima et al [2012] also observed these same circular structures, but less frequently, in retinal dystrophies other than BCD.

The degeneration in BCD seen by OCT is most prominent in the outer retina, including the photoreceptor layer, but the degeneration was not uniformly distributed.

Vision impairment. The majority of affected individuals have onset of disease during the second or third decade of life; however, age of onset, presenting symptoms, and disease severity vary widely. Marked asymmetry between eyes is common. Symptoms include:

  • Visual field loss (progressive). Visual field loss may manifest in different individuals as peripheral field loss (ring, paracentral, or central scotoma) or central or pericentral scotomas (usually associated with atrophic lesions that encroach upon the foveal region of the macula).
  • Nyctalopia (progressive). Night blindness (i.e., difficulty seeing in low light) is a nonspecific feature of BCD in that it is typical of many forms of inherited retinal degeneration.
  • Reduction in visual acuity (progressive). Visual acuity can range from normal to hand motion (HM). Although the reduction in visual acuity has been reported to typically result in legal blindness by the fifth or sixth decade, central vision can sometimes be spared even in persons with severe disease. More often loss of central visual acuity reflects atrophy or degenerative change close to or including the fovea.

Molecular Genetic Testing

Gene. CYP4V2 is the only gene in which mutations are known to cause Bietti crystalline dystrophy.

Clinical testing

  • Sequence analysis. Mutations in CYP4V2 have been reported in a high percentage of persons with Bietti crystalline dystrophy in China and Japan.

Table 1. Summary of Molecular Genetic Testing Used in Bietti Crystalline Dystrophy

Gene SymbolTest MethodMutations DetectedMutation Detection Frequency by Test Method 1
CYP4V2Sequence analysisSequence variants 2>93% 3, 4

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected.

3. Mutations were identified in 95.4% (N=109) families or 93.6% of alleles [Xiao et al 2011].

4. In a study from Japan, eight probands were found to have mutations of CYP4V2 including seven with the IVS6-8_c.810del/insGC, suggesting a founder effect.

Testing Strategy

To confirm/establish the diagnosis in a proband. In the majority of probands, the diagnosis can be established or suspected following standard evaluation procedures for inherited retinal disorders, which typically include past medical history, full ophthalmologic evaluation, visual field testing, spectral domain OCT (sdOCT), and, if available and indicated, electrophysiology.

Molecular testing (sequence analysis) of CYP4V2 confirms the clinical diagnosis in a majority of cases.

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Predictive testing for at-risk asymptomatic adult family members requires prior identification of the disease-causing mutations in the family.

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

Bietti crystalline dystrophy (BCD) is a progressive chorioretinal degeneration with onset typically during second to third decade of life, but ranging from the early teenage years to beyond the third decade. The symptoms, ranges of visual impairment, and disabilities are similar to those of individuals with autosomal recessive retinitis pigmentosa.

The presenting symptom, rate of disease progression, and disease severity are also highly variable in BCD, even among those of the same age, within the same family, and with the same CYP4V2 mutation [Lee et al 2005, Lin et al 2005, Xiao et al 2011].

The progressive atrophy and degeneration of the RPE/choroid leads to reduced visual acuity, poor night vision, abnormal retinal electrophysiology, and visual field constriction. Persons with BCD may also have impaired color vision. In early or milder stages of disease patients can drive a car; however, with time, loss of peripheral visual field, central acuity, or both result in legal blindness in most, if not all, affected individuals.

Whereas affected individuals typically have profound vision loss by the fifth or sixth decade of life, central acuity can be spared through late stages of the disease in some [Kaiser-Kupfer et al 1994, Lee et al 2005]. A recent study involving 21 families with BCD showed visual acuities ranging from normal to hand motion [Xiao et al 2011].

Visual field constriction is progressive and usually presents as scotomas that enlarge with progression of disease; central, paracentral, and ring scotomas are common.

Marked asymmetry between eyes with respect to fundus appearance, reduction in visual acuity, and visual field loss is not uncommon.

Additional potential retinal complications of BCD include choroidal neovascularization (CNV) [Atmaca et al 2007, Gupta et al 2011] and macular hole [Zhu et al 2009].

Genotype-Phenotype Correlations

Individuals with BCD who are homozygous for the c.800-1_8delTCATACAG_800_808delGTCATCGCGinsGC allele or compound heterozygous for this allele along with c.1091-1A>G appear to have a more severe form of the disease based on electrophysiologic testing. The level of visual loss in BCD is related to the severity of retinal thinning [Lai et al 2007].

Individuals with splice site mutations (i.e., homozygous c.800-1_8delTCATACAG_800_808delGTCATCGCGinsGC or compound heterozygous c.800-1_8delTCATACAG_800_808delGTCATCGCGinsGC and c.1091-1A>G) had lower EOG Arden indices and were more likely to have a nonrecordable scotopic full-field ERG and 30-Hz flicker ERG when compared with individuals harboring coding region mutations.

The high degree of clinical variability in BCD suggests that influencing factors, other than the primary CYP4V2 defect, may be at play. The uncommon cases that are regional (i.e., affect only certain regions of the retina) may represent disease associated with mutations that are associated with retention of either a small amount of functional gene product or other modifying factors. There is no evidence to suggest that mutations in any gene other than CYP4V2 cause BCD.

Prevalence

While BCD is generally considered to be a rare disease, it may be underdiagnosed. For example, in a study done by Mataftsi et al, approximately 10% of persons with autosomal recessive retinitis pigmentosa were also diagnosed with BCD [Mataftsi et al 2004]. According to Hartong et al, worldwide prevalence of retinitis pigmentosa was one in 4000, with autosomal recessive retinitis pigmentosa accounting for 50%-60% of the cases [Hartong et al 2006]. This implies a prevalence of BCD up to one in 67,000, representing almost 5,000 individuals in the US alone.

BCD appears to be more common in people of East Asian descent, particularly the Chinese and Japanese [Hu 1983]. It has also been reported in persons of Lebanese and Mexican origin [Lin et al 2005, Lai et al 2007, Zenteno et al 2008] and in persons of European origin presenting with retinitis pigmentosa [Mataftsi et al 2004].

Differential Diagnosis

Retinitis pigmentosa. The clinical symptoms and findings on visual field testing and electrophysiologic studies in Bietti crystalline dystrophy (BCD) are similar to those of other forms of retinal degeneration that fall under the category of retinitis pigmentosa and allied disorders. See Retinitis Pigmentosa Overview.

Crystalline deposits in the retina may be associated with:

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, 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 of an individual diagnosed with Bietti crystalline dystrophy (BCD), the following evaluations are recommended:

  • Fundoscopic examination
  • Full-field electroretinogram (ffERG) to establish a baseline
  • Visual field testing (perimetry) to evaluate the degree of visual field constriction or presence of scotomas and to establish a baseline
  • Optical coherence tomography (OCT) to evaluate for complications such as choroidal neovascularization (CNV) or macular hole formation
  • Medical genetics consultation

Treatment of Manifestations

No treatment for BCD currently exists; affected individuals should be referred to services specific to those with vision impairment:

  • Low vision specialists can prescribe low vision aids/devices to help optimize remaining vision.
  • State services for the Blind or organizations/professionals trained to work with the visually impaired provide access to services related to employment, education, and counseling regarding the psychosocial adaptation to visual loss

Note: Choroidal neovascularization (CNV) is uncommon in BCD. Laser photocoagulation is not usually considered for CNV in inherited forms of retinal degeneration and has recently been superseded by the use of anti-vascular endothelial growth factor (anti-VEGF) therapy in a fashion similar to its use in age-related macular dystrophy.

Surveillance

Ophthalmologic examination is recommended every one to two years to monitor disease progression. Examination should include visual field testing particularly as it relates to determination of driving eligibility and eligibility for government programs and/or disability.

Patients should be aware of the possibility of choroidal neovascularization (CNV) and the option of self-monitoring using an Amsler grid under direction of their primary care ophthalmologist.

Evaluation of Relatives at Risk

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

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

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

Bietti crystalline dystrophy (BCD) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of one mutant allele).
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. The offspring of an individual with Bietti crystalline dystrophy are obligate heterozygotes (carriers) for a disease-causing mutation in CYP4V2.

Unless an individual with Bietti crystalline dystrophy has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a disease-causing mutation in CYP4V2.

Other family members. Each sib of the proband’s parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing of at-risk relatives is possible if the disease-causing mutations in the family have been identified.

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 diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at approximately 15 to 18 weeks’ gestation or chorionic villus sampling (CVS) at approximately ten to 12 weeks’ gestation. The disease-causing mutations in the family must be identified before prenatal testing can be performed.

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 Bietti crystalline dystrophy 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 decisions about prenatal testing are 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 mutations have 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.

  • National Eye Institute
    31 Center Drive
    MSC 2510
    Bethesda MD 20892-2510
    Phone: 301-496-5248
    Email: 2020@nei.nih.gov
  • American Council of the Blind (ACB)
    2200 Wilson Boulevard
    Suite 650
    Arlington VA 22201
    Phone: 800-424-8666 (toll-free); 202-467-5081
    Fax: 202-467-5085
    Email: info@acb.org
  • 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
  • National Federation of the Blind (NFB)
    200 East Wells Street
    (at Jerigan Place)
    Baltimore MD 21230
    Phone: 410-659-9314
    Fax: 410-685-5653
    Email: pmaurer@nfb.org
  • Prevent Blindness America
    211 West Wacker Drive
    Suite 1700
    Chicago IL 60606
    Phone: 800-331-2020 (toll-free)
    Email: info@preventblindness.org
  • 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

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. Bietti Crystalline Dystrophy: Genes and Databases

Gene SymbolChromosomal LocusProtein NameLocus SpecificHGMD
CYP4V24q35​.2Cytochrome P450 4V2CYP4V2 @ LOVDCYP4V2

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 Bietti Crystalline Dystrophy (View All in OMIM)

210370BIETTI CRYSTALLINE CORNEORETINAL DYSTROPHY
608614CYTOCHROME P450, FAMILY 4, SUBFAMILY V, POLYPEPTIDE 2

Molecular Genetic Pathogenesis

Though the biochemical basis of BCD remains unknown, findings suggest that BCD may result from a systemic abnormality in lipid metabolism. There also have been reports of a missing 32-kd fatty-acid binding protein with a high affinity for fatty acids: docosahexaenoic acid (DHA; 22:6n-3), α-linolenic acid (18:3n-3), and palmitic acid (16:0) in the lymphocytes of persons with BCD compared to controls [Lee et al 1998]. Metabolic studies of fibroblasts and lymphocytes cultured from individuals with BCD exhibited altered lipid metabolism, with decreased synthesis of ω-3 polyunsaturated fatty acids (PUFAs) (e.g., eicosapentaenoic acid (EPA; 20:5n-3) and DHA) from α-linolenic acid compared to controls [Lee et al 2001].

More recently, free fatty acid profiling revealed significantly altered fatty acid concentrations in the serum of persons with BCD compared to controls. Specifically, stearic acid (18:0) was elevated and oleic acid (18:1n-9) was lowered in persons with BCD compared to controls [Lai et al 2010].

In addition to ocular tissues, transmission electron microscopy showed crystalline material of unknown lipid composition in lymphoblasts and fibroblasts of persons with BCD [Welch 1977].

Normal allelic variants. CYP4V2 spans 19 kb and comprises 11 exons [Li et al 2004]. Genetic linkage analysis first identified the BCD locus to be located on human chromosome 4q35 [Jiao et al 2000]. Fine mapping of this locus identified CYP4V2 as the gene in which mutation is responsible for BCD [Li et al 2004].

Pathologic allelic variants. A wide range of CYP4V2 mutations (>30) has now been described in individuals with BCD. At least one mutation has been reported in each of the 11 exons. See Table 3 (pdf).

The most frequent CYP4V2 mutation found in affected individuals, c.800-1_8delTCATACAG_800_808delGTCATCGCGinsGC, results in the skipping of exon 7. Eight nucleotides of the 3’ end of intron 6 and nine from the 5’ end of exon 7 are deleted along with an insertion of GC [Bietti 1937, Kaiser-Kupfer et al 1994, Lee et al 1998, Lee et al 2001, Lewis 2004, Shan et al 2005, Baer & Rettie 2006, Hardwick 2008].

Two other deletions, c.1091-1A>G and c.1226-6delTGACAG_1226_1235delCAGGTTACAG (a deletion spanning the splice acceptor site for exon 9), result in skipping of exons 9 and 10, respectively [Li et al 2004, Shan et al 2005].

Six more nonsense mutations and 23 missense mutations have also been described [Li et al 2004, Lee et al 2005, Lin et al 2005, Shan et al 2005, Wada et al 2005, Lai et al 2007, Hardwick 2008, Zenteno et al 2008, Xiao et al 2011].

Table 2. Selected CYP4V2 Pathologic Allelic Variants

DNA Nucleotide Change
(Alias 1)
Protein Amino Acid ChangeReference Sequences
c.327+1G>A
(IVS2+1G>A)
See footnote 2NM_207352​.3
NP_997235​.3
c.800-1_8delTCATACAG_800_808delGTCATCGCGinsGC 3
(IVS6-8 del/insGC)
See footnote 3
c.1091-1A>G
(ISV8-2A>G)
See footnote 4
c.1226-6delTGACAG_1226_1235delCAGGTTACAG 5
(IVS9-6del)
See footnote 5

Note on variant classification: Variants listed in the table have been provided by the author(s). 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. Variant designation that does not conform to current naming conventions

2. Skipping of exon 2, resulting in a frameshift in which the exon 1 sequence is followed by four novel amino acids and a premature terminating [Li et al 2004].

3. Skipping of exon 7, which encodes 62 amino acids [Wada et al 2005]

4. Skipping of exon 9, which encodes 62 amino acids

5. Skipping of exon 10, which encodes 60 amino acids [Shan et al 2005]

Normal gene product. The cytochrome P450 4V2 protein (CYP4V2) is 525 amino acids. This protein is a member of the CYP superfamily of heme-containing monooxygenases. CYP4V2 is a fatty acid oxidase, with preferential activity for ω-hydroxylation of saturated, medium-chain fatty acids [Nakano et al 2009]. Homology modeling predicts that the CYP4V2 structure contains a transmembrane segment located near the amino terminus with a globular structural domain following that is typical of cytochrome P450 enzymes. The globular domain of CYP4V2 comprises 18 helices and β structural elements [Li et al 2004]

Abnormal gene product. There is no published evidence that the abnormal gene product causes disease through loss of function.

Mutations resulting from exon 7, 9, and 10 skipping and mutations resulting from the exon 2 splicing that predicts premature termination are expected to cause gross structural changes in any translated protein with resulting loss of enzyme activity.

Similarly, several amino acid deletions and substitutions would be predicted to negatively affect CYP4V2 activity, based on their conservation across other CYP4 enzymes and homology modeling [Li et al 2004].

Exon-skipping mutations are predicted to lead to more severe forms of the disease than are missense mutations, which lead to homozygous or heterozygous amino acid substitutions [Li et al 2004, Lai et al 2007].

Defects in the catalytic function of this enzyme lead to altered fatty acid metabolism; the endogenous substrate(s) have yet to be identified.

References

Literature Cited

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Suggested Reading

  1. Nakamura M, Lin J, Nishiguchi K, Kondo M, Sugita J, Miyake Y. Bietti crystalline corneoretinal dystrophy associated with CYP4V2 gene mutations. Adv Exp Med Biol. 2006;572:49–53. [PubMed: 17249554]

Chapter Notes

Author Notes

For interested parties:

Ed Kelly's Web site
Dick Weleber's Web site

Acknowledgments

Supported in part by a Center Grant from Foundation Fighting Blindness, Columbia, MD) and an unrestricted grant from Research to Prevent Blindness (New York, NY)

Revision History

  • 14 June 2012 (cd) Revision: prenatal testing available
  • 12 April 2012 (me) Review posted live
  • 31 October 2011 (ek) Original submission
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