Oculocutaneous Albinism Type 2 (OCAII) via the OCA2 Known Intragenic Gross Deletion

Oculocutaneous albinism (OCA) is an inherited disorder caused by deficiency in melanin synthesis that results in hypopigmentation of the skin, eyes, and hair. If the phenotype is mainly restricted to the eyes and the optic system, it is referred to as ocular albinism (OA) (Gargiulo et al. 2011). The reduction or complete absence of melanin pigment in the developing eye leads to foveal hypoplasia and misrouting of the optic nerves in the affected individuals (Oetting and King 1999). The eye and optic system abnormalities that are common to all types of albinism are nystagmus, photophobia, strabismus, moderate to severe impairment of visual acuity, reduced iris pigment with iris translucency, reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination, refractive errors and altered visual evoked potentials (VEP). The degree of skin and hair hypopigmentation varies with the type of OCA (Lewis 2012). To date, four types of non-syndromic OCA (type I-IV) have been described. Among these, OCAII (tyrosinase-positive) is the most prevalent type and twice as common as compared to OCAI in African and African-American populations (Durham-Pierre et al. 1994), with estimated incidence of 1: 4,000-10,000. In the USA, the estimated prevalence of OCA2 is 1:36,000 (Grønskov et al. 2007).

OCA is genetically heterogeneous. The major autosomal recessive forms OCA I and II are caused by genetic variations in TYR and OCA2, respectively. OCA2 (previously known as P-gene) encodes the integral melanosomal membrane protein, which is hypothesized to play an essential role in maintaining the pH of the melanosomes (Brilliant 2001). The frequency of OCAII is greatly increased in patients with Angelman and Prader-willi syndromes due to the deletion of chromosome 15q ( the region that comprises the OCA2 gene) (Lee et al. 1994). A gross deletion (reported as 2.7-kb interstitial deletion allele) of the OCA2 gene accounts for 65% and 92% of mutant alleles in two African countries, Zimbabwe and Cameroon, respectively (Puri et al. 1997). 

A known interstitial deletion allele (reported as ~2.7kb) of the OCA2 gene accounts for 65% and 92% of mutant alleles in two African countries, Zimbabwe and Cameroon, respectively (Puri et al. 1997).

This test involves amplification of patient DNA with a specific pair of PCR primers (P1 through P4) that flank the common OCA2 deletion. From chromosomes carrying the homozygous deletion, 1.4 and 1.8 kb PCR products are produced with P1 and P2, respectively. No PCR product is generated with P3 and P4 sets. In the case of heterozygous deletion, P1 and P2 give PCR products ~1.4 or 1.8 kb and P3 and P4 give PCR products ~0.6 or 1.1 kb. In normal chromosomes, only ~0.6 and 1.1 kb PCR products are generated by P3 and P4.