OCA2 gene

• Overview
• Albinism
• Additional information
• References

Overview

Gene (OMIM no.)	OCA2 (#611409)
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 features	The 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 diagnosis	Next generation sequencing Targeted gene panels (albinism) Whole exome sequencing Whole genome sequencing
Management	Management of albinism
Therapies under research	Current research in albinism
Further information	Medline Plus

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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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