Alternative titles; symbols
SNOMEDCT: 63450009; ORPHA: 79433; DO: 0070097;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9p23 | Albinism, oculocutaneous, type III | 203290 | Autosomal recessive | 3 | TYRP1 | 115501 |
A number sign (#) is used with this entry because of evidence that oculocutaneous albinism-3 is caused by homozygous or compound heterozygous mutation in tyrosinase-related protein-1 (TYRP1; 115501) on chromosome 9p23.
For a discussion of genetic heterogeneity of OCA, see OCA1A (203100).
This form of albinism was referred to as 'rufous oculocutaneous albinism (ROCA)' when it was found in southern African blacks. In blacks the disorder is characterized by bright copper-red coloration of the skin and hair and dilution of the color of the iris. Manga et al. (1997) suggested that albinism caused by mutation in the TYRP1 gene should be referred to as OCA3.
Among 79 albinos in Nigeria, King et al. (1978) identified 23 with a seemingly 'new' variety of tyrosinase-positive oculocutaneous albinism. Sun sensitivity was less marked. In 86%, retinal pigment was present on funduscopy. Nystagmus was present in 22 and strabismus in 12. In New York City rather numerous cases are seen in Puerto Rican families from the Aguadilla-Arecibo area of northwestern Puerto Rico. Albinism in dark-skinned persons such as Puerto Ricans is not always obvious because freckled skin and reddish hair may be present. Red reflex on transillumination of the iris and nystagmus are important clues to the diagnosis. See King et al. (1985) for a full description.
Boissy et al. (1996) described a set of African American fraternal twins, one of whom had light brown skin and hair and blue-gray irides with a red reflex consistent with brown oculocutaneous albinism. The unaffected twin had dark hair and skin pigment. The affected twin developed bilateral nystagmus by the age of 1 year. Family history indicated that a sib and the maternal grandmother were born with hypopigmentation associated with an increase in pigmentation with age. Boissy et al. (1996) used foreskins to develop melanocyte cultures. Melanocytes from the twins exhibited similar amounts of soluble melanin in the supernatants, but there was a 93% reduction in the amount of insoluble melanin in melanocytes from the affected twin. Ultrastructural studies of cultured melanocytes revealed that the melanocytes of the affected twin contained only early melanosomes, whereas melanocytes cultured from normal African American individuals contain numerous fully matured and pigmented stage IV melanosomes.
Segregation analysis in 18 Nigerian OCA families led King and Rich (1986) to conclude that the trait is autosomal recessive with an estimated gene frequency of 0.025 +/- 0.007 in that population.
Manga et al. (1997) stated that oculocutaneous albinism is the most common autosomal recessive disorder among southern African blacks. Three forms account for almost all OCA cases. Tyrosinase-positive OCA (OCA2; 203200), which is the most common, is caused by mutations in the P gene on chromosome 15 (e.g., 611409.0001). Brown OCA (BOCA; see 203200) and rufous OCA (ROCA) account for most of the remaining cases. The frequency of ROCA is approximately 1 in 8,500.
By linkage analysis in 9 ROCA families, Manga et al. (1997) showed that the ROCA phenotype was linked to an intragenic marker at the TYRP1 locus and obtained a maximum lod score of 3.80 at theta = 0.00.
The transmission pattern of OCA3 in the family reported by Chiang et al. (2009) was consistent with autosomal recessive inheritance.
Boissy et al. (1996) found that cultured melanocytes from an African American male with OCA, whose fraternal twin brother was unaffected, showed an absence of immune-reactive TYRP1 (115501). Analysis of mRNA revealed that transcription of TYRP1 was completely absent. Through amplification of exons by PCR for SSCP analysis, the affected twin was found to be homozygous for a 1-bp deletion in the TYRP1 gene (368delA; 115501.0001), resulting in premature termination at codon 384.
Manga et al. (1997) analyzed the TYRP1 gene in 19 unrelated southern African blacks with rufous OCA (ROCA) and identified compound heterozygosity for 368delA and a nonsense mutation (S166X; 115501.0002) in 17 of the 19 patients; the remaining 2 patients carried the 1-bp deletion but no mutations were identified in the other allele. Manga et al. (1997) noted that 16 of the 19 unrelated individuals could be classified unambiguously as having ROCA, with red-bronze skin and ginger hair; however, visual anomalies were not always detectable: approximately 76% of these individuals had nystagmus, and only 14% had strabismus. In 1 family, 2 sibs displayed an atypical form of albinism involving hair that was similar to that found in OCA2 (203200) individuals but slightly red, whereas the skin was a much lighter, red-yellow color than is typical of the ROCA tinge; they were compound heterozygotes for 368delA and S166X in TYRP1, but were also found to be heterozygous for the common 2.7-kb deletion in the P gene (OCA2; 611409.0001). Manga et al. (1997) suggested that ROCA caused by mutations in the TYRP1 gene should be designated OCA3.
Rooryck et al. (2006) studied a Caucasian German boy with yellow-gold hair with orange highlights, fair eyelashes, blue-green eyes with defects of the iris and nystagmus, several pigmented nevi, and pale yellow skin that did not tan but burned easily. No mutations were found in the TYR (606933) and OCA2 genes, but the patient was compound heterozygous for a missense mutation inherited from his mother (R356E; 115501.0004) and a de novo 1-bp deletion (106delT; 115501.0005) in the TYRP1 gene. Rooryck et al. (2006) noted that except for the unusual hair color, the phenotype in this patient was virtually identical to that seen in OCA1B (606952) or OCA2.
In a boy of Asian Indian origin with reddish hair color, brown irides, nystagmus, and lightly pigmented skin, who was negative for mutations in the TYR, OCA2, and SLC45A2 (606202) genes, Chiang et al. (2009) identified homozygosity for a 4-bp deletion in the TYRP1 gene (115501.0006). The unaffected parents were both heterozygous for the deletion.
Barnicot (1957) suggested that this is a genetic trait distinct from albinism.
Barnicot, N. A. Human pigmentation. Man 57: 114-120, 1957.
Boissy, R. E., Zhao, H., Oetting, W. S., Austin, L. M., Wildenberg, S. C., Boissy, Y. L., Zhao, Y., Sturm, R. A., Hearing, V. J., King, R. A., Nordlund, J. J. Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as 'OCA3.' Am. J. Hum. Genet. 58: 1145-1156, 1996. [PubMed: 8651291]
Chiang, P.-W., Spector, E., Scheuerle, A. A case of Asian Indian OCA3 patient. (Letter) Am. J. Med. Genet. 149A: 1578-1580, 2009. [PubMed: 19533799] [Full Text: https://doi.org/10.1002/ajmg.a.32930]
King, R. A., Cervenka, J., Okoro, A. N., Witkop, C. J., Jr. The brown albino: a new type of tyrosinase-positive oculocutaneous albinism. (Abstract) Am. J. Hum. Genet. 30: 56A only, 1978.
King, R. A., Creel, D., Cervenka, J., Okoro, A. N., Witkop, C. J. Albinism in Nigeria with delineation of new recessive oculocutaneous type. Clin. Genet. 17: 259-270, 1980. [PubMed: 6768477] [Full Text: https://doi.org/10.1111/j.1399-0004.1980.tb00145.x]
King, R. A., Lewis, R. A., Townsend, D., Zelickson, A., Olds, D. P., Brumbaugh, J. Brown oculocutaneous albinism: clinical, ophthalmological, and biochemical characterization. Ophthalmology 92: 1496-1505, 1985. [PubMed: 3935994] [Full Text: https://doi.org/10.1016/s0161-6420(85)33832-0]
King, R. A., Rich, S. S. Segregation analysis of brown oculocutaneous albinism. Clin. Genet. 29: 496-501, 1986. [PubMed: 3742854] [Full Text: https://doi.org/10.1111/j.1399-0004.1986.tb00550.x]
Manga, P., Kromberg, J. G. R., Box, N. F., Sturm, R. A., Jenkins, T., Ramsay, M. Rufous oculocutaneous albinism in southern African blacks is caused by mutations in the TYRP1 gene. Am. J. Hum. Genet. 61: 1095-1101, 1997. [PubMed: 9345097] [Full Text: https://doi.org/10.1086/301603]
Rooryck, C., Roudaut, C., Robine, E., Musebeck, J., Arveiler, B. Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient. Pigment Cell Res. 19: 239-242, 2006. [PubMed: 16704458] [Full Text: https://doi.org/10.1111/j.1600-0749.2006.00298.x]