Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in Japan

Inagaki, Katsuhiko; Suzuki, Tamio; Shimizu, Hiroshi; Ishii, Norihisa; Umezawa, Yoshinori; Tada, Jôji; Kikuchi, Noriaki; Takata, Minoru; Takamori, Kenji; Kishibe, Mari; Tanaka, Michi; Miyamura, Yoshinori; Ito, Shiro; Tomita, Yasushi

doi:10.1086/382195

Cited by 135 publications

(160 citation statements)

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“…30 OCA4 is one of the most common forms of albinism in the Japanese population. 31,32 Polymorphism within the SLC45A2 gene is a major determinant of normal variation in skin pigmentation, 33 with the rs16891982 b.1122G/C, p.374Leu/Phe change of the encoded protein, MATP, associated with the lighter pigmentation phenotypes of Europeans. 24 A heavier OCA pigmentation phenotype has been noted as being linked with darker familial background pigmentation, indicating that other genes may modify the OCA condition.…”

Section: Introductionmentioning

confidence: 99%

Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

et al. 2009

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Oculocutaneous albinism type 2 (OCA2) is a human autosomal-recessive hypopigmentation disorder associated with pathological mutations of the OCA2 gene. In this study, we investigated a form of OCA in a Polynesian population with an observed phenotype characterized by fair skin, some brown nevi present in the sun-exposed areas and green or blue eyes. Hair presented with a unique red coloration since birth, with tones ranging across individuals from Yellow-Red to Brown-Red, or Auburn. We genetically screened for mutations in the OCA2 and MC1R genes as their products have previously been shown to be associated with red hair/fair skin and OCA2. The SLC45A2 gene was also screened to identify any possible relation to skin color variation. We have identified a novel missense substitution in the OCA2 gene (Gly775Asp) responsible for OCA2 in individuals of Polynesian heritage from Tuvalu. The estimated incidence of this form of OCA2 in the primary study community is believed to occur at one of the highest recorded rates of albinism at approximately 1 per 669 individuals. In addition, we have analyzed four unrelated individuals with albinism who have Polynesian heritage from three other separate communities and found they carry the same OCA2 mutation. We also analyzed an out-group comprising three unrelated individuals with albinism of Melanesian ancestries from two separate communities, one Australian Aboriginal and three Australian Caucasians, and did not detect this mutation. We hypothesize that this mutation may be Polynesian specific and that it originated from a common founder.

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Section: Introductionmentioning

confidence: 99%

Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

et al. 2009

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“…Mutations in Slc45a2 have been identified in an increasing number of animal species [9,10,26,27,33,37], and the phenotype of Slc45a2 varies from hypopigmentation as severe as that seen in OCA1 to some pigmentation with brown hair and eyes [13]. The OCAO suncus described herein, having almost pure white coats, may serve as a unique disease model of human OCA4 and will provide some insights to the function of SLC45A2.…”

Section: Discussionmentioning

confidence: 80%

“…Homologous mutations affecting the aspartic acid in the fourth transmembrane domain, resulting in light beige and cream coat colors, have been reported in the mouse (uw dbr ) and horse, respectively [26,27,40]. Moreover, D157N, a missense mutation that lies in the second cytoplasmic loop close to the fourth transmembrane domain, is the most frequent mutation in Japanese OCA4 patients [13]. However, functional studies of these mutant SLC45A2s have not been reported.…”

Section: Discussionmentioning

confidence: 99%

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Oculocutaneous Albinism in Suncus murinus: Establishment of a Strain and Identification of Its Responsible Gene

et al. 2009

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Abstract:The house musk shrew Suncus murinus (Insectivora, Soricidae) is referred to as suncus in a laboratory context. Although the capture of albino-like shrews (wild suncus) has been reported previously, albino-like strains have never been established, and the molecular basis of the character has remained elusive. We have established an OCAO mutant strain (oculocutaneous albinism Okinawa), from a wild suncus with a white coat and red eyes, which was captured in 2002. During the course of establishing the strain, it was revealed that the albino-like phenotype was inherited in an autosomal recessive manner. To elucidate the molecular basis of this phenotype, we cloned the suncus cDNAs for tyrosinase (Tyr), pinkeyed dilution (p), and solute carrier family 45, member 2 (Slc45a2), since these genes are involved in oculocutaneous albinism in various species, including humans. Several polymorphisms were identified in these genes; however, linkage analysis excluded the involvement of Tyr and p. On the other hand, two amino acid substitutions (V240A and G366E) were identified in Slc45a2 that cosegregated with the phenotype in the OCAO mutant strain. While V240A was also present in colored suncus collected from Okinawa, G366E was unique to the albino-like suncus and heterozygous carriers. Thus, we conclude that a mutation in Slc45a2 (G366E) is responsible for an albino-like phenotype in Suncus murinus.

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“…OCA3 is rare, with notable frequency only in African populations (3). The incidence of OCA4 is not known; however, it appears to be more prevalent in Japanese populations (7).…”

Section: Oculocutaneous Albinismmentioning

confidence: 99%

Informed reasoning: repositioning of nitisinone to treat oculocutaneous albinism

Manga

Orlow²

2011

J. Clin. Invest.

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Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by hypopigmentation of the skin, hair, and eyes. Affected individuals experience reduced visual acuity and substantially increased skin cancer risk. There are four major types of OCA (OCA1-OCA4) that result from disruption in production of melanin from tyrosine. Current treatment options for individuals with OCA are limited to attempts to correct visual problems and counseling to promote use of sun protective measures. However, Onojafe et al., reporting in this issue of the JCI, provide hope for a new treatment approach for OCA, as they demonstrate that treating mice that model OCA-1b with nitisinone, which is FDA approved for treating hereditary tyrosinemia type 1, elevates plasma tyrosine levels, and increases eye and hair pigmentation. Oculocutaneous albinismMelanin is a biopolymer synthesized from tyrosine. Upon synthesis, it is deposited in specialized organelles (melanosomes) in neural crest-derived melanocytes found in the skin, hair follicles, iris, uveal tract, and inner ear as well as in retinal pigmented epithelium (RPE) derived from the optic cup. Oculocutaneous albinism (OCA) denotes a group of common autosomal-recessive disorders that result from disruption of melanin synthesis. There are four major forms: OCA1, which is caused by mutations in the tyrosinase gene (TYR) (1); OCA2, caused by mutations in OCA2 (2); OCA3, caused by mutations in the tyrosinase-related protein 1 gene (TYRP1) (3); and OCA4, caused by mutations in the solute carrier family 45, member 2 gene (SLC45A2) (4). OCA1 affects approximately 1 in 40,000 people worldwide and is the most prevalent form of OCA among individuals of mixed European descent. OCA2 affects 1 in 39,000 such individuals, with substantially higher prevalence in AfricanAmerican and Amerindian populations. The carrier rate of a pathogenic deletion of OCA2 in African-American newborns is estimated to be 1 in 235 (5); rates in some Amerindian populations reach 1 in 200 (6). OCA3 is rare, with notable frequency only in African populations (3). The incidence of OCA4 is not known; however, it appears to be more prevalent in Japanese populations (7).OCAs are characterized by decreased or absent melanin in skin, hair, and eyes. In skin, melanin plays a central role in protection from UV-induced carcinogenesis. Thus, individuals with OCA are highly susceptible to skin cancers, particularly squamous cell carcinoma. During embryogenesis, melanin synthesis in the RPE affects development of the fovea and of adjacent retinal ganglion cells, which in turn regulate decussation of the nerve connecting the retina to brain at the optic chiasm. Numerous structural abnormalities ensue if melanogenesis is deficient. In the adult eye, melanin appears important for reducing light scatter and aiding acuity. Individuals with OCA consequently suffer from nystagmus, strabismus, photophobia, and loss of visual acuity that can be severe enough to render them legally blind (8).The highly visible OCA phenotypemost dram...

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Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in Japan

Cited by 135 publications

References 11 publications

Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

Oculocutaneous Albinism in Suncus murinus: Establishment of a Strain and Identification of Its Responsible Gene

Informed reasoning: repositioning of nitisinone to treat oculocutaneous albinism

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