Oculocutaneous albinism type 3

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The oculocutaneous albinism type 3 (OCA3) is a form of oculocutaneous albinism , which leads to brightened skin and hair color. It is based on premature STOP codons in the TYRP1 gene, which codes for the enzyme DHICA oxidase .

Synonyms are: oculocutaneous albinism, red; Oculocutaneous albinism, more xanthous; ROCA (Rufous Oculocutaneous Albinism)

Appearance

Oculocutaneous albinism type 3 (OCA 3) was first described genetically in 1996. In people from dark-skinned peoples, it usually leads to a red OCA (rufous OCA or ROCA) with red or red-brown skin, ginger-colored or red hair and a hazelnut-colored iris. Therefore, when this form of albinism was first observed in 1918, it was called xanthism . The changes to the optical apparatus are often less pronounced or not at all pronounced. In contrast, a brown OCA was found in the case described first. Since the twin was not further examined later in life, it is possible that his appearance may later have evolved to the red OCA.

genetics

OCA 3 is based on premature STOP codons in the TYRP1 gene. The TYRP1 gene is located on chromosome 9 (9p23). Other names of the gene are: CAS2, CATB, GP75, TRP, TRP1, TYRP, b-PROTEIN. It corresponds to the so-called brown gene of the mouse on chromosome 4, since mutations in this gene lead to the brown coat color in the mouse. DHICA oxidase is very similar to tyrosinase , is found in the membrane of the melanosomes and supports tyrosinase in its work.

physiology

TYRP1 (5,6-dihydroxyindole-2-carboxylic acid oxidase) is specifically expressed in the dye- producing cells, the melanocytes , and has a function in the production of the dye melanin . Both apply to the other, structurally similar members of this TRP gene family, which also includes tyrosinase and DCT ( dopachrome tautomerase , TYRP2). Like these, TYRP1 has a transmembrane domain, two metal binding sites, and a cysteine-rich epidermal growth factor motif, and all three are found in the membrane of the melanosomes. Despite these similarities within the TRP family, the function of TYRP1 differs significantly from the different functions of the other two.

TYRP1 oxidizes dihydroxyindolecarboxylic acid (DHICA) and promotes the polymerization of DHICA monomers to melanin. In addition, DHICA oxidase stabilizes tyrosinase and other melanosome enzymes.

Usually (allele B) the black eumelanin is densely and regularly arranged in the melanosomes so that they are black and egg-shaped. The recessive allele b loosens the melanin, making the melanosomes appear brown. The various mutations of the brown locus therefore lighten black fur to dark to light brown.

frequency

OCA3 affects 1 in 8,500 people in Africa, while it is very rare in Caucasian and Asian populations.

In animals: brown locus (B)

Mutation of the brown locus in a cat

The oculocutaneous albinism type 3 (OCA3) corresponds to the brown locus in mammals.

Brown mice, rats and rabbits are significantly heavier than black ones.

Domestic cat

There is also a mutation of this gene in cats that causes it to lighten from black to brown.

Domestic dog

Gończy Polski : The adult dog is black with brandy. In the puppy lying next to it, the eumelanin is lightened by the brown gene, so it is red with fire. Note that the eyes and nose are also lightened, while the light fur on the legs, which is due to pheomelanin, remains unchanged.

Many hunting dog breeds have animals that have been lightened from black to brown or red by one or more of the alleles of the brown locus. There are four alleles b s , b d b c and the dominant, non-highlighted wild type B.

See main article: Dogs' coat colors

Domestic pig

No alleles are known on the brown locus in pigs with the exception of the allele B k , which leads to the development of brown spots on a red background.

Domestic cattle

In Dexter cattle , the light brown color is caused by a mutation in the TRP1 gene.

literature

  • B. Käsmann-Kellner: Albinism: Much more than just blue eyes. In: Ophthalmologist. 104 (8), 2007, pp. 646-647 doi: 10.1007 / s00347-007-1588-8
  • B. Käsmann-Kellner, B. Seitz: Phenotype of the visual system in oculocutaneous and ocular albinism. In: Ophthalmologist. 104 (8), 2007, pp. 648-661. doi: 10.1007 / s00347-007-1571-4

Individual evidence

  1. ^ Albinism, oculocutaneous, type 3. In: Orphanet (database for rare diseases).
  2. ↑ a b Aleksandra Lipka: Albinism: search for mutations in the TRP-1 gene. Dissertation . University of Lübeck, 2004.
  3. ↑ a b K. Grønskov, J. Ek, K. Brondum-Nielsen: Oculocutaneous albinism. In: Orphanet J Rare Dis. 2007 Nov 2; 2, p. 43. Review. PMID 17980020
  4. ↑ Takeshi Kobayashi, Genji Imokawa, Dorothy C. Bennett, and Vincent J. Hearing: Tyrosinase Stabilization by Tyrp1 (the brown Locus Protein). In: J Biol Chem . Vol. 273, Issue 48, pp. 31801-31805, November 27, 1998 PMID 9822646 .
  5. ↑ T. Kobayashi, VJ Hearing: Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo . In: J. Cell. Sci. tape 120 , Pt 24, December 2007, p. 4261-4268 , doi : 10.1242 / jcs.017913 , PMID 18042623 .
  6. ↑ a b c d Krista Siebel: Analysis of genetic variants of loci for the coat color and their relationships to the color phenotype and to quantitative performance characteristics in pigs. Inaugural dissertation . Institute for Animal Science at the Humboldt University in Berlin, 2001.
  7. ^ A. Schmidt-Küntzel, E. Eizirik, SJ O'Brien, M. Menotti-Raymond: Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. In: J Hered. 2005 Jul-Aug; 96 (4), pp. 289-301. PMID 15858157
  8. ↑ LA Lyons, IT Foe, HC Rah, RA Grahn: Chocolate coated cats: TYRP1 mutations for brown color in domestic cats. In: Mamm Genome. 2005 May; 16 (5), pp. 356-366. PMID 16104383
  9. ↑ Sheila Schmutz: Dog Coat Color Genetics. Brown. last updated on July 1, 2006.
  10. ^ Sheila Schmutz: Genetics of Coat Color Patterns in Cattle. Status: January 19, 2005.

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