Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

Abstract

The primary pigment that determines human skin, hair and eye colour is melanin, which is synthesised by melanocytes. Melanin protects the skin from ultraviolet (UV) radiation and there is an inverse correlation between the degree of constitutive pigmentation and the risk of sun-induced skin cancers. Besides the life-threatening cancer risk, loss of pigmentation results in premature aging, compromised cutaneous immunity and significant emotional distress to affected individuals. [1][2][3] During embryonic development, melanocyte precursors that arise from the neural crest populate several areas including the interfollicular epidermis and hair follicle bulge in the skin; the uveal tract of the eye; and the stria vascularis, vestibular apparatus and endolymphatic sac of the ear. The development of melanocytes is tightly regulated at the genetic level by a number of genes that control proliferation, survival and migration of precursor cells to the various sites of the body and their differentiation into active melanocytes. A key regulator of this process is the microphthalmia transcription factor (MITF), which has been dubbed the 'master regulator' of the melanocyte, capable of modulating expression of several melanocytespecific proteins.[4] MITF mutations result in Waardenburg syndrome type II.[5] Once the melanocyte has differentiated, MITF regulates expression of genes in response to UV exposure, facilitating the tanning response.Melanocytes produce two forms of melanin, black-brown eumelanin and red-yellow pheomelanin. Skin and hair colour Corresponding author: P Manga (prashiela.manga@nyumc.org)Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 -2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in...

Visual Status and Visual Challenges of Persons with Albinism in A Metropolitan City of Niger Delta Region, Nigeria

“…In Oculocutaneous albinism, the hair, skin and eyes are affected while in Ocular albinism the features is confined to the eyes and visual system [2]. The most common variants of albinism and their responsible genes are: Ocular albinism (OA1gene), OCA1 (Tyrosine TYR gene), OCA2/Brown OCA (P gene)-which is the commonest in Africa, OCA3/Rufous OCA (Tyrosine-related protein-1, TRP-1 gene) and OCA4 (SLC45A2 gene) [3][4][5].…”

Pigmentation and vision: Is GPR143 in control?

“…The function of TRP1 is in the biosynthesis of melanin from tyrosine, TRP1 catalyzes the oxidation of 5–6‐dihydroxyindole‐2‐carboxylic acid to an indole that participates in the polymerization of melanin (Hearing & Tsukamoto, ; Ito, ), depicted in Figure . and it has an incidence rate of 1:8,500 in Africa (Kromberg et al, ; Manga, Kerr, Ramsay, & Kromberg, ). OCA3 has a less severe phenotype than other forms of OCA.…”

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“…This therefore excludes the disparities seen among racial groups that have a purely biological and/or genetic basis, e.g. oculocutaneous albinism type 2, which is fairly common among black Africans, but almost never affects whites, [21] or melanoma, which is prevalent among SA white women but almost never affects black African, coloured or Indian women. [22] There are several ways in which the SA healthcare system has been unjust, particularly to black citizens.…”