TYRP1 gene

Overview

Gene (OMIM no.)
Function of gene/protein
  • Protein: tyrosinase-related protein 1
  • Involved in eumelanin synthesis in melanosomes along with tyrosinase
  • Catalyses the oxidation of catalysing the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) monomers into eumelanin (Gronskov 2007)
  • Also involved in maintaining stability of tyrosinase and melanosome ultrastructure
Clinical phenotype (with OMIM phenotype no.)
  • Albinism, oculocutaneous, type III; OCA1A (#203290)
  • [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)] (#612271)
Inheritance
  • Autosomal recessive
Ocular featuresThe ocular phenotype and visual function are highly variable among individuals but tend to be less severe overall than other OCA types. They may have some/all of the following features:
  • Decreased visual acuity
  • Nystagmus
  • Strabismus
  • Photophobia
  • Iris transillumination
  • Foveal hypoplasia
  • Fundal hypopigmentation
  • Chiasmal misrouting detected on visual evoked potential (VEP) testing due to abnormally increased number of axons crossing the optic chiasm to innervate the contralateral cortex
Systemic features
  • “Rufous” OCA
  • Predominantly affects Africans
  • Reddish brown/lightly pigmented skin in non-Africans
  • Red/reddish yellow (ginger) hair with orange highlights
Key investigations
  • Orthoptic assessment and refraction
  • OCT to detect foveal hypoplasia
  • Electrophysiology (pattern/flash VEP) to detect chiasmal misrouting
  • Eye movement recordings
  • Systemic assessment with dermatologists and other relevant specialist if syndromic OCA (e.g. Hermansky-Pudlak or Chediak-Higashi syndrome) is suspected
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (albinism)
  • Whole exome sequencing
  • Whole genome sequencing
Management
Therapies under research
Further information

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Additional information

OCA3 affects predominantly Africans, with a prevalence of up to 1:8500 being reported[6] but cases have been reported in other ethnicities as well.[710] There are two common variants among southern Africans, p.S166X and c.368delA, both of which are nonsense mutations and account for 90% of rufous OCA among that population.[11]

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References

  1. Wiriyasermkul P, Moriyama S, Nagamori S. Membrane transport proteins in melanosomes: Regulation of ions for pigmentation. Biochim Biophys Acta Biomembr. 2020;1862(12):183318.
  2. Grønskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007;2(43).
  3. Sarangarajan R, Boissy RE. Tyrp1 and oculocutaneous albinism type 3. Pigment Cell Res. 2001;14(6):437-444.
  4. Boissy RE, Zhao H, Oetting WS, et al. 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. 1996;58(6):1145-1156.
  5. Manga P, Kerr R, Ramsay M, Kromberg JG. Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa. S Afr Med J. 2013;103(12 Suppl 1):984-988. Published 2013 Jul 29.
  6. Kromberg JG, Castle DJ, Zwane EM, et al. Red or rufous albinism in southern Africa. Ophthalmic Paediatr Genet. 1990;11(3):229-235.
  7. Forshew T, Khaliq S, Tee L, et al. Identification of novel TYR and TYRP1 mutations in oculocutaneous albinism. Clin Genet. 2005;68(2):182-184.
  8. Kausar T, Jaworek TJ, Tariq N, et al. Genetic studies of TYRP1 and SLC45A2 in Pakistani patients with nonsyndromic oculocutaneous albinism. J Invest Dermatol. 2013;133(4):1099-1102.
  9. Rooryck C, Roudaut C, Robine E, Müsebeck J, Arveiler B. Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient. Pigment Cell Res. 2006;19(3):239-242.
  10. Chiang PW, Spector E, Scheuerle A. A case of Asian Indian OCA3 patient. Am J Med Genet A. 2009;149A(7):1578-1580.
  11. Manga P, Kromberg JG, Box NF, Sturm RA, Jenkins T, Ramsay M. Rufous oculocutaneous albinism in southern African Blacks is caused by mutations in the TYRP1 gene. Am J Hum Genet. 1997;61(5):1095-1101.

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Updated on April 6, 2022
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