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Oculocutaneous Albinism Type 4

Synonym: OCA4

, MD, PhD and , MD, PhD.

Author Information

Initial Posting: ; Last Update: September 7, 2017.

Summary

Clinical characteristics.

Oculocutaneous albinism type 4 (OCA4) is characterized by hypopigmentation of the hair and skin plus the characteristic ocular changes found in all other types of albinism, including: nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia associated with reduction in visual acuity; and misrouting of the optic nerves at the chiasm associated with alternating strabismus, reduced stereoscopic vision, and an altered visual evoked potential (VEP). Individuals with OCA4 are usually recognized within the first year of life because of hypopigmentation of the hair and skin and the ocular features of nystagmus and strabismus. Vision is likely to be stable after early childhood. The amount of cutaneous pigmentation in OCA4 ranges from minimal to near normal. Newborns with OCA4 usually have some pigment in their hair, with color ranging from silvery white to light yellow. Hair color may darken with time, but does not vary significantly from childhood to adulthood.

Diagnosis/testing.

Because the phenotype of OCA4 overlaps that of the other genetic forms of albinism (oculocutaneous and ocular), the diagnosis of OCA4 is established by molecular genetic testing with the identification of biallelic pathogenic variants in SLC45A2. A multigene panel or comprehensive genomic testing is the preferred molecular genetic testing method for this disorder.

Management.

Treatment of manifestations: Correction of refractive errors with spectacles or contact lenses to improve visual acuity. Strabismus surgery may be considered for cosmetic reasons. Dark glasses may alleviate photophobia but may reduce vision; a hat with a brim or visor best achieves reduction in photophobia. Protection from the sun, through the wearing of protective clothing and the regular application of sunscreen, is essential.

Prevention of secondary complications: Individuals with OCA4 should stay out of the sun from an early age, because cumulative ultraviolet exposure is a major risk factor for skin cancers.

Surveillance: Annual ophthalmologic examination and reassessment for accurate correction of refractive error. Evaluation of the skin for cancer screening every six months is recommended.

Agents/circumstances to avoid: Prolonged exposure to sun.

Genetic counseling.

OCA4 is typically inherited in an autosomal recessive manner. The parents of a proband are obligate heterozygotes and thus carriers of one SLC45A2 pathogenic variant. Heterozygotes (carriers) are asymptomatic and not at risk of developing the disorder, but may be light in pigmentation for their ethnic group. 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 family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

Diagnosis

Suggestive Findings

Oculocutaneous albinism type 4 (OCA4) should be suspected in individuals with the following clinical features:

  • Hypopigmentation of the skin and hair varying from complete depigmentation to partial depigmentation with brown hair. In some individuals pigmentation increases during the first decade of life [Suzuki & Tomita 2008].
  • Characteristic ocular changes found in all types of albinism, including the following findings detected on routine ophthalmologic examination:
    • Nystagmus
    • Reduced iris pigment with iris translucency
    • Reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination
    • Foveal hypoplasia associated with reduction in visual acuity
  • Vision abnormalities (due to misrouting of the optic nerves at the chiasm) including:
    • Alternating strabismus
    • Reduced stereoscopic vision
    • Altered visual evoked potential (VEP)
      Note: (1) A VEP is not necessary for the routine diagnosis of albinism; misrouting is implied by the finding of strabismus and reduced stereoscopic vision. (2) In some individuals, particularly those who have moderate amounts of cutaneous and retinal pigment, or those who have foveal hypoplasia and no obvious nystagmus, a VEP may be necessary to demonstrate misrouting of the optic nerves. (3) The VEP is performed with a technique specifically developed for demonstration of the misrouting and a regular VEP will not demonstrate this. (4) Normal routing of the optic nerves, demonstrated with a VEP, indicates that the diagnosis is not albinism/OCA.

Establishing the Diagnosis

The diagnosis of OCA4 is established in a proband with characteristic clinical findings and/or by identification of biallelic pathogenic variants in SLC45A2 on molecular genetic testing (see Table 1).

Molecular genetic testing approaches can include the use of a multigene panel or comprehensive genomic testing.

Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of OCA4 overlaps that of the other genetic forms of albinism (oculocutaneous and ocular), a multigene panel or comprehensive genomic testing (when available) is the preferred molecular genetic testing method for this disorder. Single-gene testing (sequence analysis of SLC45A2, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.

  • A multigene panel that includes SLC45A2 and other genes of interest associated with albinism (see Differential Diagnosis) may be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • Comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation).
    For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

For this disorder a multigene panel that also includes deletion/duplication analysis or exome array is recommended if no or only one pathogenic variant is identified.

Table 1.

Molecular Genetic Testing Used in OCA4

Gene 1Test MethodProportion of Pathogenic Variants 2 Detectable by This Method
SLC45A2Sequence analysis 375%-85% 4
Gene-targeted deletion/duplication analysis 5Rare 6
1.
2.

See Molecular Genetics for information on allelic variants.

3.

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

4.
5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

6.

Rooryck et al [2008] identified deletion of exon 4 in SLC45A2 in an individual who was described as having a severe phenotype at birth which became milder with age.

Note: Oki et al [2017] reported a multigenerational family in which OCA4 appeared to be inherited as an autosomal dominant condition associated with a heterozygous pathogenic variant in SLC45A2. The authors of this GeneReview feel that this may represent a rare occurrence, but note that no functional assay for the specific variant was performed and that concomitant heterozygous pathogenic variant(s) in a regulatory region or in other (unknown) OCA-related genes cannot be ruled out.

Clinical Characteristics

Clinical Description

A wide range of clinical phenotypes has been recognized to date [Suzuki & Tomita 2008]. The amount of cutaneous pigmentation in OCA4 is a continuum from minimal to near normal [Newton et al 2001, Inagaki et al 2004, Rundshagen et al 2004, Ikinciogullari et al 2005, Inagaki et al 2005]. The amount of iris and retinal pigment varies and visual acuity covers a wide range; however, no subtypes of OCA4 are recognized.

Individuals with albinism (including OCA4) are usually recognized within the first year of life because of the ocular features of nystagmus and strabismus. In many families, particularly in those with darker constitutional pigmentation, the cutaneous hypopigmentation is also obvious at birth and suggests the diagnosis.

Eye

Nystagmus. Some children with albinism have nystagmus that is noticed by the parents and the examining physician in the delivery room. Many children with albinism do not have nystagmus at birth and the parents note slow wandering eye movements and a lack of visual attention. The parents may become concerned because the child does not seem to "focus well," but the absence of nystagmus may delay the diagnosis. Most children with albinism develop nystagmus by age three to four months, and the diagnosis is often considered at the four-to-six month well-baby check-up. The nystagmus can be rapid early in life and generally slows with time; however, nearly all individuals with albinism have nystagmus throughout their lives. Nystagmus is more noticeable when individuals are tired, angry, or anxious, and less marked when they are well rested and feeling well [Summers 2009].

Iris color ranges from blue to brown. In one individual with OCA4, who had been misdiagnosed at birth as having OCA1 because of complete iris transillumination, the amount of iris pigment increased in the first ten years, resulting in blue iris color [Suzuki et al 2005].

Visual acuity in individuals with OCA4 ranges from 20/30 to 20/400 and is usually in the range of 20/100 to 20/200 [Rundshagen et al 2004, Suzuki et al 2005]. Vision is likely to be stable after early childhood and no major change or further reduction in vision should occur; loss of vision later in life is generally not related to the albinism.

Hair/Skin

The range of hair and skin pigment in individuals with OCA4 is broad [Newton et al 2001, Inagaki et al 2004, Rundshagen et al 2004, Ikinciogullari et al 2005, Inagaki et al 2005].

Hair. Individuals with OCA4 are often born with some pigment in their hair that ranges in color from silvery white to light yellow.

  • Scalp hair may be very light, but it is usually not completely white (not as white as a sheet of paper or fresh snow); some parents may refer to light yellow/blond hair color as "white" or "nearly white" if it is very lightly pigmented or is much lighter than the hair color of other family members at a similar age.
  • Furthermore, the definition of "white" scalp hair is not easy in some young children because the hair may be sparse and short and because some shampoos discolor hair.
  • It is helpful to hold a piece of white paper next to the hair to determine if it is truly white.
  • Hair color may darken with time, but usually the hair color does not change dramatically between childhood and adulthood [Inagaki et al 2004].

Skin. When hair color is blond or yellow, the skin is usually creamy white with little or no pigmentation. When hair color is somewhat darker, the skin is usually similar to that seen in unaffected individuals [Thody et al 1991].

Skin color in individuals with OCA4 is not usually as white as that in individuals with the OCA1A subtype of oculocutaneous albinism type 1, reflecting the fact that skin melanocytes in individuals with OCA4 can still synthesize some melanin; however, the majority of the melanin is yellow pheomelanin rather than black-brown eumelanin.

Skin cancer risk. Over many years, exposure of lightly pigmented skin to the sun can result in coarse, rough, thickened skin (pachydermia), solar keratoses (premalignant lesions), and skin cancer. Both basal cell carcinoma and squamous cell carcinoma can develop. The incidence rate of melanoma in individuals with OCA is unknown; however, the risk for melanoma in this population is generally considered to be higher than in unaffected individuals [Streutker et al 2000, Asuquo et al 2009].

Skin cancer is unusual in individuals with OCA4 in the US because of the availability of sunscreens, the social acceptability of wearing clothes that cover most of the exposed skin, and the fact that individuals with albinism often do not spend a great deal of time outside in the sun. Skin cancer in an individual with any type of OCA is very rare in northern areas of the US. Skin cancer in individuals with albinism is common particularly in some parts of Africa because of the increased amount of sun exposure throughout the year, the cultural differences in protective dress, and lack of skin-protective agents such as sunscreens. In addition, African individuals with albinism tend to have poorer prognosis with skin cancer because of late presentation to care and failure to complete treatment for economic reasons [Mabula et al 2012].

Genotype-Phenotype Correlations

The lack of a functional assay for the SLC45A2 protein and the limited data from SLC45A2 molecular genetic testing make genotype-phenotype correlations difficult [Newton et al 2001, Rundshagen et al 2004, Ikinciogullari et al 2005, Inagaki et al 2005, Konno et al 2009].

Two common pathogenic alleles, p.Asp157Asn and p.Gly188Val, have been reported in Japanese individuals. The p.Asp157Asn allele may have very low functional activity in melanogenesis; p.Gly188Val may have some residual functional activity [Inagaki et al 2004].

Recently, a family with autosomal dominant OCA4 has been reported [Oki et al 2017], with a novel heterozygous pathogenic variant: c.208T>C (p.Tyr70His). Family members with the variant demonstrate a relatively mild phenotype, with a slightly creamy complexion, brown to black hair, and mild iris hypopigmentation.

The degree of cutaneous pigmentation, ocular pigmentation, and visual development resulting from particular SLC45A2 pathogenic variants cannot be predicted at this time.

Nomenclature

The ocular features of all types of oculocutaneous albinism (OCA) and X-linked ocular albinism (OA1) are similar and the terms "oculocutaneous albinism" and "albinism" can be used interchangeably when referring to these clinical features.

Prevalence

Prevalence of OCA4 is thought to be on the order of 1:100,000 in most populations throughout the world. It is likely to be more common in Japan, where it accounts for 24% of individuals with OCA [Inagaki et al 2004, Inagaki et al 2005].

OCA4 has also been described in individuals of German, Turkish, Korean, Indian, Chinese, Danish, and Moroccan descent [Newton et al 2001, Rundshagen et al 2004, Ikinciogullari et al 2005, Suzuki et al 2005, Sengupta et al 2007, Grønskov et al 2009, Konno et al 2009].

Differential Diagnosis

Table 2.

Disorders to Consider in the Differential Diagnosis of OCA4

DisorderGene(s)MOIClinical Features of This Disorder
Overlapping w/OCA4Distinguishing from OCA4
OCA1TYRAROculocutaneous albinismMay have poorer visual acuity
OCA2OCA2AROculocutaneous albinismNA
OCA3
(OMIM 203290)
TYRP1AROculocutaneous albinismReddish hair & freckled skin; only described in individuals from African, Pakistani, German, Indian, & Japanese populations
OCA5
(OMIM 615312)
Unknown (candidate region is on 4q24)AROculocutaneous albinismGolden hair
OCA6
(OMIM 113750)
SLC24A2AROculocutaneous albinismIndistinguishable because of the functional similarity of SLC45A2 (OCA4) and SLC24A2
OCA7
(OMIM 615179)
C10orf11AROculocutaneous albinismRelatively severe impaired visual acuity
Hermansky-Pudlak syndrome (HPS)HPS1
AP3B1 (HPS2)
HPS3
HPS4
HPS5
HPS6
DTNBP1 (HPS7)
BLOC1S3 (HPS8)
BLOC1S6 (PLDN)
HPS10
AROculocutaneous albinismBleeding tendency, platelet dense granules; granulomatous colitis & interstitial pneumonia in HPS1 and HPS4; immunodeficiency & hemophagocytic syndrome in HPS2 & HPS10
OA1GPR143XLOcular albinismHypopigmentation of skin & hair
FRMD7-related infantile nystagmusFRMD7XLNystagmusOculocutaneous albinism

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with oculocutaneous albinism type 4 (OCA4), the following evaluations are recommended if they have not already been completed:

  • Complete ophthalmologic evaluation including measurement of visual acuity and refractive error
  • Assessment for strabismus
  • Assessment by dermatologist to instruct parents regarding use of sun-protective clothing, lotions, and formulas
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Ophthalmologic care is the most important part of the ongoing care for most individuals with OCA4.

The majority of individuals with albinism have significant hyperopia or myopia and astigmatism. Correction of these refractive errors with spectacles or contact lenses can improve visual acuity. Except in the very unusual individual, correction of refractive errors cannot restore visual acuity to normal because of the foveal hypoplasia.

The alternating strabismus found in most individuals with albinism is generally not associated with the development of amblyopia. Strabismus surgery is usually not required, but can be considered for cosmetic reasons if the strabismus is marked or fixed.

Photophobia is common in individuals with OCA4, but the degree of discomfort varies and does not depend entirely on the amount of melanin pigment present in the iris or skin. In general, opaque contact lenses or darkly tinted lenses do not improve visual function. Dark glasses may be helpful for individuals with albinism, but many prefer to go without dark glasses because of the reduction in vision from the dark lenses. A hat with a brim (e.g., a baseball hat with a visor) is often the best way to achieve reduction in photophobia and sun protection.

Protection from the sun through the wearing of protective clothing and the regular application of sunscreen is essential to prevent sunburn and secondary skin changes, and to decrease the risk of skin cancer in later life. Regular skin check-ups for skin cancer are recommended for adult individuals with OCA4, especially in cases of severe hypopigmentation.

Prevention of Secondary Complications

Individuals with OCA4 should stay out of the sun from an early age, as cumulative ultraviolet exposure is a major risk factor for skin cancers (see Skin Cancer Risk).

Prolonged periods in the sun require skin protection with clothing (hats with brims, long sleeves and pants, socks) and sunscreen with a high SPF number (total blocks with SPF 45-50+). There is no scientific evidence to indicate how high an SPF value is enough; individuals with OCA4 should use sunscreen with higher SPF values (45-50+) to lessen as much as possible the cumulative effect of ultraviolet to their skin.

Surveillance

Annual ophthalmologic examination and reassessment for accurate correction of refractive error are appropriate.

There is no definitive guideline supported by scientific evidence as to how often an individual should be evaluated by a dermatologist, though an evaluation of the skin for cancer screening every six months is recommended.

Agents/Circumstances to Avoid

Avoid prolonged exposure of the skin to the sun.

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 in the US and www.ClinicalTrialsRegister.eu in Europe 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

OCA4 is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected individual are obligate heterozygotes (i.e., carriers of one SLC45A2 pathogenic variant).
  • Heterozygotes (carriers) are asymptomatic and not at risk of developing the disorder; they may be light in pigmentation for their ethnic group.

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.
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder, although they may be light in pigmentation for their ethnic group.

Offspring of a proband. Unless an individual with OCA4 has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a pathogenic variant in SLC45A2.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier of a SLC45A2 pathogenic variant.

Carrier (Heterozygote) Detection

Carrier testing for at-risk relatives requires prior identification of the SLC45A2 pathogenic variants 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.

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 and Preimplantation Genetic Diagnosis

Once the SLC45A2 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.

A fetal skin biopsy will not provide an accurate diagnosis and is not appropriate for prenatal diagnosis of OCA4.

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. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

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.

  • Albinism Database
    University of Minnesota
    MN
  • National Organization of Albinism and Hypopigmentation (NOAH)
    PO Box 959
    East Hampstead NH 03826-0959
    Phone: 800-473-2310 (toll-free); 603-887-2310
    Fax: 800-648-2310 (toll-free)
    Email: info@albinism.org
  • National Library of Medicine Genetics Home Reference
  • PanAmerican Society for Pigment Cell Research (PASPCR)
  • 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.

Oculocutaneous Albinism Type 4: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Oculocutaneous Albinism Type 4 (View All in OMIM)

606202SOLUTE CARRIER FAMILY 45, MEMBER 2; SLC45A2
606574ALBINISM, OCULOCUTANEOUS, TYPE IV; OCA4

Molecular Genetic Pathogenesis

The phenotype resulting from heterozygosity of a single Slc45a2 pathogenic variant in mice results in hypopigmentation that may be analogous to some of the autosomal dominant forms of albinism reported in humans. Apparent autosomal dominant inheritance of OCA4 has been recently reported in a single Japanese family [Oki et al 2017].

Gene structure. SLC45A2 has seven exons and spans 40 kb at chromosome 5p13.3 (NM_016180.3).

Pathogenic variants. See International Albinism home page. Fifty-three pathogenic variants of SLC45A2 have been reported. Most are missense variants, but deletions of one or a small number of bases and base changes have been detected [Newton et al 2001, Inagaki et al 2004, Rundshagen et al 2004, Ikinciogullari et al 2005, Inagaki et al 2005, Suzuki et al 2005, Sengupta et al 2007, Grønskov et al 2009, Konno et al 2009]. The most common SLC45A2 pathogenic variant in Japanese individuals, accounting for 39% of pathogenic alleles, is the p.Asp157Asn missense variant [Inagaki et al 2004].

Most individuals with OCA4 are compound heterozygotes for SLC45A2 pathogenic variants. Approximately 17% of reported Japanese individuals and a cohort from India have only one identifiable pathogenic variant; the second variant could not be detected with the methods used [Inagaki et al 2004, Sengupta et al 2007]. (For more information, see Table A.).

Table 3.

SLC45A2 Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.208T>Cp.Tyr70HisNM_016180​.3
NP_057264​.3
c.469G>Ap.Asp157Asn
c.563G>Tp.Gly188Val

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 (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

Normal gene product. The MATP protein consists of 530 amino acids, contains 12 transmembrane domains, and is only expressed in mealocytes (NP_057264.3) [Newton et al 2001]. The precise function of the MATP protein is yet to be elucidated, although it appears to play a role in tyrosinase processing, intracellular trafficking of tyrosinase to melanosome, and regulating tyrosinase activity through controlling melanomal pH [Costin et al 2003, Bin et al 2015].

Abnormal gene product. The mechanisms by which the abnormal protein alters the ability of the cell to synthesize melanin are unknown. However, tyrosinase, the rate-limiting enzyme in the biosynthesis of melanin that is associated with OCA1, appears to be mislocalized in mouse melanocytes that are homozygous for pathogenic SLC45A2 alleles [Costin et al 2003]. This phenotype is shared with melanocytes that contain pathogenic variants in OCA2, the gene associated with OCA2 [Toyofuku et al 2002].

References

Literature Cited

  • Asuquo ME, Ngim O, Ebughe G, Bassey EE. Skin cancers amongst four Nigerian albinos. Int J Dermatol. 2009;48:636–8. [PubMed: 19538377]
  • Bin BH, Bhin J, Yang SH, Shin M, Nam YJ, Choi DH, Shin DW, Lee AY, Hwang D, Cho EG, Lee TR. Membrane-Associated Transporter Protein (MATP) regulates melanosomal pH and influences tyrosinase activity. PLoS One. 2015;10:e0129273. [PMC free article: PMC4461305] [PubMed: 26057890]
  • Costin GE, Valencia JC, Vieira WD, Lamoreux ML, Hearing VJ. Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4. J Cell Sci. 2003;116:3203–12. [PubMed: 12829739]
  • Grønskov K, Ek J, Sand A, Scheller R, Bygum A, Brixen K, Brondum-Nielsen K, Rosenberg T. Birth prevalence and mutation spectrum in Danish patients with autosomal recessive albinism. Invest Ophthalmol Vis Sci. 2009;50:1058–64. [PubMed: 19060277]
  • Hutton SM, Spritz RA. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. J Invest Dermatol. 2008;128:2442–50. [PMC free article: PMC3515683] [PubMed: 18463683]
  • Ikinciogullari A, Tekin M, Dogu F, Reisli I, Tanir G, Yi Z, Garrison N, Brilliant MH, Babacan E. Meningococccal meningitis and complement component 6 deficiency associated with oculocutaneous albinism. Eur J Pediatr. 2005;164:177–9. [PubMed: 15565285]
  • Inagaki K, Suzuki T, Ito S, Suzuki N, Fukai K, Horiuchi T, Tanaka T, Manabe E, Tomita Y. OCA4: evidence for a founder effect for the p.D157N mutation of the MATP gene in Japanese and Korean. Pigment Cell Res. 2005;18:385–8. [PubMed: 16162179]
  • Inagaki K, Suzuki T, Shimizu H, Ishii N, Umezawa Y, Tada J, Kikuchi N, Takata M, Takamori K, Kishibe M, Tanaka M, Miyamura Y, Ito S, Tomita Y. Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan. Am J Hum Genet. 2004;74:466–71. [PMC free article: PMC1182260] [PubMed: 14961451]
  • Konno T, Abe Y, Kawaguchi M, Storm K, Biervliet M, Courtens W, Kono M, Tomita Y, Suzuki T. Oculocutaneous albinism type IV: A boy of Moroccan descent with a novel mutation in SLC45A2. Am J Med Genet A. 2009;149A:1773–6. [PubMed: 19610114]
  • Mabula JB, Chalya PL, Mchembe MD, Jaka H, Giiti G, Rambau P, Masalu N, Kamugisha E, Robert S, Gilyoma JM. Skin cancers among Albinos at a university teaching hospital in Northwestern Tanzania: a retrospective review of 64 cases. BMC Dermatol. 2012;12:5. [PMC free article: PMC3483204] [PubMed: 22681652]
  • Mauri L, Manfredini E, Del Longo A, Veniani E, Scarcello M, Terrana R, Radaelli AE, Calò D, Mingoia G, Rossetti A, Marsico G, Mazza M, Gesu GP, Cristina Patrosso M, Penco S, Piozzi E, Primignani P. Clinical evaluation and molecular screening of a large consecutive series of albino patients. J Hum Genet. 2017;62:277–90. [PubMed: 27734839]
  • Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, Brilliant MH. Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4. Am J Hum Genet. 2001;69:981–8. [PMC free article: PMC1274374] [PubMed: 11574907]
  • Oki R, Yamada K, Nakano S, Kimoto K, Yamamoto K, Kondo H, Kubota T. A Japanese family with autosomal dominant oculocutaneous albinism type 4. Invest Ophthalmol Vis Sci. 2017;58:1008–16. [PubMed: 28192564]
  • Rooryck C, Morice-Picard F, Elcioglu NH, Lacombe D, Taieb A, Arveiler B. Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes and practical aspects. Pigment Cell Melanoma Res. 2008;21:583–7. [PubMed: 18821858]
  • Rundshagen U, Zuhlke C, Opitz S, Schwinger E, Kasmann-Kellner B. Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4. Hum Mutat. 2004;23:106–10. [PubMed: 14722913]
  • Sengupta M, Chaki M, Arti N, Ray K. SLC45A2 variations in Indian oculocutaneous albinism patients. Mol Vis. 2007;13:1406–11. [PubMed: 17768386]
  • Streutker CJ, McCready D, Jimbow K, From L. Malignant melanoma in a patient with oculocutaneous albinism. J Cutan Med Surg. 2000;4:149–52. [PubMed: 11003720]
  • Summers CG. Albinism: classification, clinical characteristics, and recent findings. Optom Vis Sci. 2009;86:659–62. [PubMed: 19390472]
  • Suzuki T, Inagaki K, Fukai K, Obana A, Lee ST, Tomita Y. A Korean case of oculocutaneous albinism type IV caused by a D157N mutation in the MATP gene. Br J Dermatol. 2005;152:174–5. [PubMed: 15656822]
  • Suzuki T, Tomita Y. Recent advances in genetic analyses of oculocutaneous albinism types 2 and 4. J Dermatol Sci. 2008;51:1–9. [PubMed: 18407468]
  • Thody AJ, Higgins EM, Wakamatsu K, Ito S, Burchill SA, Marks JM. Pheomelanin as well as eumelanin is present in human epidermis. J Invest Dermatol. 1991;97:340–4. [PubMed: 2071942]
  • Toyofuku K, Valencia JC, Kushimoto T, Costin GE, Virador VM, Vieira WD, Ferrans VJ, Hearing VJ. The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase. Pigment Cell Res. 2002;15:217–24. [PubMed: 12028586]
  • Wei A, Yang X, Lian S, Li W. Implementation of an optimized strategy for genetic testing of the Chinese patients with oculocutaneous albinism. J Dermatol Sci. 2011;62:124–7. [PubMed: 21458243]

Suggested Reading

  • Konno T, Abe Y, Kawaguchi M, Kondo T, Tomita Y, Suzuki T. Functional analysis of OCA4 mutant sequences using under white mouse melanocytes. Pigment Cell Melanoma Res. 2009;22:235–7. [PubMed: 19220778]
  • Li H, Meng S, Zheng H, Wei H, Zhang Y. A Chinese case of oculocutaneous albinism type 4 with two novel mutations. Int J Dermatol. 2008;47:1198–201. [PubMed: 18986462]

Chapter Notes

Author History

Murray H Brilliant, PhD; University of Wisconsin School of Medicine (2005-2011)
Masahiro Hayashi, MD, PhD (2011-present)
Tamio Suzuki, MD, PhD (2011-present)

Revision History

  • 7 September 2017 (ha) Comprehensive update posted live
  • 15 September 2011 (cd) Revision: deletion/duplication analysis of SCL45A2 available clinically
  • 5 May 2011 (me) Comprehensive updated posted live
  • 14 June 2007 (cd) Revision: sequence analysis and prenatal diagnosis available clinically
  • 17 November 2005 (me) Review posted to live Web site
  • 21 April 2005 (mb) Original submission
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