OCA2 gene

Overview

Gene (OMIM no.)
Function of gene/protein
  • Protein: OCA2 melanosomal transmembrane protein
  • Exact function not fully understood
  • Appears to be involved in regulating the pH of melanosomes as neutral pH is critical for melanin synthesis 
Clinical phenotype (with OMIM phenotype no.)
  • Albinism, oculocutaneous, type II (#203200)
  • Albinism, brown oculocutaneous (#20320)
  • [Skin/hair/eye pigmentation 1, blond/brown hair, blue/non-blue eyes] (#227220)
Inheritance
  • Autosomal recessive
Ocular featuresThe ocular phenotype and visual function are highly variable among individuals affected by OCA2. 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
Signs for CSNB
  • Normal fundal appearance
Systemic features
  • Highly variable skin and hair phenotypes but tends to demonstrate accumulation of pigmentation over time due to accumulation of phenomelanin
  • Classic OCA2: creamy white or tan skin with freckles usually; yellow/blonde/light brown hair, eyebrows and eyelashes
  • Brown OCA2: patients may appear normal with brown skin and hair but appears hypopigmented compared to unaffected family members
  • Patients with concomitant mutations in the MC1R gene usually have red hair
  • The MC1R protein in melanocytes regulates the production of MITF protein, which in turn regulates the expression of tyrosinase
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

Type 2 oculocutaneous albinism (OCA2) accounts for 30% of albinism cases worldwide.[9] It is very common among Africans or those of African origin, with an estimated prevalence ranging from around 1 in 10,000 cases among African Americans in the United States to around 1 in 3,900 cases in certain populations in sub-Saharan Africa. This is mainly due to the high frequency of an intragenic 2.7 kilobase deletion which results in the removal of exon 7 in the OCA2 gene in Africa. [10,11]

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References

  1. Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA. Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics 1995;26(2):354-363.
  2. Lee ST, Nicholls RD, Bundey S, Laxova R, Musarella M, Spritz RA. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. N Engl J Med. 1994;330(8):529-534.
  3. Rosemblat S, Durham-Pierre D, Gardner JM, Nakatsu Y, Brilliant MH, Orlow SJ. Identification of a melanosomal membrane protein encoded by the pink-eyed dilution (type II oculocutaneous albinism) gene. Proc Natl Acad Sci U S A. 1994;91(25):12071-12075.
  4. Wiriyasermkul P, Moriyama S, Nagamori S. Membrane transport proteins in melanosomes: Regulation of ions for pigmentation. Biochim Biophys Acta Biomembr. 2020;1862(12):183318. 
  5. Rinchik EM, Bultman SJ, Horsthemke B, et al. A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature. 1993;361(6407):72-76.
  6. Federico JR, Krishnamurthy K. Albinism. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 27, 2021.
  7. King RA, Willaert RK, Schmidt RM, et al. MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2). Am J Hum Genet. 2003;73(3):638-645.
  8. Chan HW, Schiff ER, Tailor VK, et al. Prospective Study of the Phenotypic and Mutational Spectrum of Ocular Albinism and Oculocutaneous Albinism. Genes (Basel). 2021;12(4):508.
  9. Simeonov DR, Wang X, Wang C, et al. DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. Hum Mutat. 2013;34(6):827-835.
  10. Durham-Pierre D, Gardner JM, Nakatsu Y, et al. African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism. Nat Genet. 1994;7(2):176-179.
  11. Stevens G, Ramsay M, Jenkins T. Oculocutaneous albinism (OCA2) in sub-Saharan Africa: distribution of the common 2.7-kb P gene deletion mutation. Hum Genet. 1997;99(4):523-527. 

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Updated on April 5, 2022
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