Patients with albinism have a normal number of melanocytes in the epidermis and follicles, but the melanin pigment is totally or partially absent. Philadelphia, PA: Saunders Elsevier; Albinism: classification, clinical characteristics, and recent findings.
Optom Vis Sci. Oculocutaneous albinism. J Eur Acad Dermatol Venereol. Individuals with oculocutaneous albinism are unable to oxidize tyrosine into dopa through tyrosinase. This inability to produce pigment causes pale complexion, white or fair hair, and red eyes, as light reflects blood vessels in the retina, or greenish-blue or light brown eyes, if there is pigment formation in the iris. In fact, the phenotypic variability of albinism is broad, ranging from complete absence of pigmentation of the hair, skin, and eyes to mild depigmentation Figs.
Orphanet J Rare Dis. Albinism and its implications with vision. Figure 1 Phenotype in albinism. Wide phenotypic variability among children with albinism. Figure 2 Phenotype in albinism. Wide phenotypic variability among women with albinism. Figure 3 Phenotype in albinism. Wide phenotype variability among men with albinism.
Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet UV radiation and are at greater risk of actinic damage. Genetic skin diseases predisposing to basal cell carcinoma. Eur J Dermatol. A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Exp Dermatol. Clinical management should include education of albinos and family members on the importance of preventing sun exposure and about methods to protect against UV radiation.
Many albinos develop actinic keratosis or skin cancers before reaching the age of 30 years. Genetics of oculocutaneous albinism. Skin cancers among albinos at a university teaching hospital in Northwestern Tanzania: a retrospective review of 64 cases. BMC Dermatol. Skin cancers in albinos in a teaching Hospital in Eastern Nigeria - presentation and challenges of care. World J Surg Oncol. The sequelae of skin cancer are among the leading causes of early death in albino patients.
Skin cancer occurs in young adults among albino patients with non-photoprotected exposure to sun. In those patients, skin cancer is invariably multiple and biologically aggressive in nature, although melanoma is rare. The cancer typically occurs on the head or neck, areas usually more exposed to solar radiation. Given their high sensitivity to UV light, albinos need total sun protection and should undergo regular skin exams every six months or less.
Reduced visual acuity, refractive errors, iris translucency, nystagmus, foveal hypoplasia, fundus hypopigmentation, and abnormal decussation of optic nerve fibers at the chiasm are also common features in albinos. This misrouting is characterized by excessive crossing of fibers at the optic chiasm, which can result in strabismus and reduced stereoscopic vision. In addition, photophobia may be severe.
Albinism can occur in syndromic and non-syndromic forms. In syndromic forms of albinism such as the Hermansky-Pudlak and Chediak-Higashi subtypes, hypopigmentation and visual impairments coexist with more severe pathological abnormalities. Hermansky-Pudlak syndrome can present with immunological changes, interstitial pulmonary fibrosis, granulomatous colitis, and hemorrhagic diathesis secondary to platelet alterations.
Chediak-Higashi syndrome, besides hypopigmentation, can manifest with hematologic changes, high susceptibility to infections, bleeding, and neurological problems.
The Hermansky-Pudlak syndrome. Bull Soc Belge Ophtalmol. Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.
Am J Hum Genet. A clinical variant of familial Hermansky-Pudlak syndrome. J Dermatol. Chediak-Higashi syndrome: four cases from Northern Finland. Acta Paediatr. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; Oculocutanneous albinism. The pigmentary system. Malden, MA: Wiley-Blackwell; To date, 19 genes have been linked to the different clinical presentations of albinism, including seven for OCA. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.
A locus was also mapped in the region of the human chromosome 4q24, the genetic cause of OCA5. Mutational analysis of oculocutaneous albinism: a compact review. Biomed Res Int. However, there remain a substantial number of albinism cases without molecular identification, suggesting that more genes are associated with the condition. In addition, the lack of knowledge of the underlying mechanisms by which a genetic mutation induces a deleterious functional effect on the gene's product implies that the disorder cannot yet be fully understood.
In Brazil, albinism is clinically diagnosed based on the presence of typical cutaneous abnormalities and ocular findings. The distinction between albinism subtypes based on clinical characteristics and the broad phenotypic heterogeneity of the disorder hinders the establishment of phenotypic and genetic correlations, and there is extensive overlapping of different forms of the disease. Molecular studies to define the exact type of mutation are therefore necessary.
However, this test is currently not available under the Brazilian public health system. Albinism is a genetic disorder that affects individuals of all social classes and countries worldwide, albeit at different prevalence rates. Oculocutaneous albinism in southern Africa: population structure, health and genetic care. Ann Hum Biol. Cuna moon-child albinism, J Hered. High rates have also been reported in Africa. In Tanzania, Luande et al.
The Tanzanian human albino skin. Natural history. In sub-Saharan Africa, to , are affected by albinism. A review study published in revealed that seven publications contained epidemiological data on the prevalence of albinism in South Africa, Zimbabwe, Tanzania, and Nigeria. Albinism in Africa as a public health issue. BMC Public Health. The prevalence of albinism in these studies ranged from , in the mid-eastern state of Nigeria 27 27 Okoro AN.
Albinism in Nigeria. A clinical and social study. Br J Dermatol. Oculocutaneous albinism in an isolated Tonga community in Zimbabwe.
J Med Genet. Albinism is considered a relatively common hereditary condition among populations of South Africa. Besides the limited geographical mobility, consanguinity, together with other traditional marriage practices, may also be pertinent factors in assessments of current and future trends of albinism prevalence.
Prevalence of albinism in the South African negro. S Afr Med J. The frequency of different types of OCA differs according to the population. J Invest Dermatol. Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA genes and practical aspects. Pigment Cell Melanoma Res. Hum Genet. This is largely due to a highly frequent deletion of OCA2 found in the African population.
African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism. Nat Genet. An intragenic deletion of the P gene is the common mutation causing tyrosinase-positive oculocutaneous albinism in southern African negroids. Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan. OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q Clin Genet.
Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. SLC24A5 mutations are associated with non-syndromic oculocutaneous albinism. Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. Lessons of a day hospital: comprehensive assessment of patients with albinism in a European setting.
Chediak-Higashi syndrome is universally rare and is described in some European regions and Asia. In Brazil, the epidemiology of albinism has not been mapped. The incidence is thought to be higher in regions with a greater prevalence African descent, such as the Northeast. The population of Bahia, Brazil's third most populous state, is mostly of African or mixed descent.
Owing to the high presence of African ancestry and the fact the region was the point of entry for African slaves during the colonial period, Bahia is believed to have the highest incidence of albinos in the country. Rev Cienc Med Biol. The districts with higher albinism rates had a high proportion of African descent. Given its small population and remote location, consanguinity is high and the supposed rate of albinism in the s and s was considered one of the highest in the world.
G1; The few studies and reports available in the scientific literature suggest that figures for albinism in Brazil resemble those of Africa. However, it is unclear whether these numbers reflect the true situation in the country, highlighting the need for the government to register albinism in official databases or conduct population-based studies that provide a reliable estimate of these figures.
Thus, there is a general paucity of studies mapping the epidemiology of albinism in Brazil. Further studies are needed to provide a deeper understanding on the distribution and incidence of this genetic disorder in the country and the consequent devising of more objective and assertive strategies for the condition. The occurrence of albinism is associated with difficulties and disadvantages, resulting from the genetic disorder and social segregation.
There is stigma related to the disease that affects albinos and their families. These factors contribute to an increase in the morbimortality associated with the condition, including actinic damage and skin cancer. Skin pigmentation varies among individuals and is determined by multiple factors, including the number and metabolic activity of melanocytes in the base layer of the epidermis, the melanogenic activity of melanosomes within these melanocytes, and variations in the number, size, and distribution of melanosomes.
Differences in types of melanin, the degree of branching of the dendritic protrusions of melanocytes, and in the transport of melanosomes from these protrusions to keratinocytes also affect skin pigmentation. Genetics of pigmentation in skin cancer - a review. Mutat Res. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation.
Head Face Med. Melanocytes have an ectodermic origin in the neural crest, evolving with cutaneous hair, skin or extracutaneous eyes, cochlea, leptomeninges migration.
Some genes control the proliferation and differentiation of cells from the neural crest and regulate the migration of precursor melanocytes to their final positions. MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med. Key discoveries in melanocyte development. After differentiation of melanocytes, MITF regulates the expression of genes during exposure to ultraviolet radiation UVR , promoting tanning of the skin. Biology and genetics of oculocutaneous albinism and vitiligo - common pigmentation disorders in Southern Africa.
Melanin is a polymer pigment produced in melanocytes. Its synthesis occurs through enzyme reactions, which convert tyrosine into melanin through the tyrosinase enzyme. Cytokines and growth factors from the environment and the degree of basal activity of tyrosinase, of tyrosinase-related protein 1 TRP1 , and of membrane-associated transporter proteins are additional factors regulating this biosynthesis.
One of the important functions of melanin is to protect the skin and eyes from the harmful effects of UV. The melanin produced through this modulation is transferred to adjacent keratinocytes, where a covering around the nucleus is thus formed, protecting the DNA from damage induced by UV radiation.
Keratinocyte-melanocyte interactions during melanosome transfer. Pigment Cell Res. The degree of skin pigmentation is inversely correlated with risk of sun-induced skin cancer. Genetically, albinism is classified according to the type of genetic mutation present.
Molecular basis of type I tryrosinase-related oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene. Hum Mutat. Tyrosine is the critical enzyme in the biosynthesis of the brownish-black eumelanin and yellow pheomelanin.
Hereditary nonmelanoma skin cancer. Semin Cutan Med Surg. OCA2 is the most prevalent form of albinism in Africa. The disorder affects those of African descent more often than Caucasians and is characterized by mutation in the OCA2 gene previously known as the P gene , which encodes the P protein.
Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree. J Dermatol Sci. Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa. Albinos with the OCA2 phenotype have no eumelanin, but have some degree of pheomelanin, which can progressively increase with age. Oculocutaneous albinism and skin cancer risk. TYPR1 is an enzyme that stabilizes tyrosinase. Mutations in TYPR1 are associated with the early degradation of tyrosinase and late maturation of melanosomes.
MATP acts as a melanosomal membrane transporter protein necessary for melanin biosynthesis. The OCA5 phenotype is linked to a specific, as yet unidentified gene, mapped to the region of the 4q24 chromosome, which was discovered in members of a consanguineous Pakistani family. Increasing the complexity: new genes and new types of albinism. In early , a team of Chinese researchers reported the use of exome sequencing to reveal the molecular basis of albinism in an affected family. Recent results indicate an important role of SLC24A5 in the maturation of melanosomes, melanosomal architecture, and in proper melanin biosynthesis.
Animal studies have revealed that mutation of this gene leads to a reduction in the size and density of melanosomes. Also in , a new gene associated with albinism was discovered among individuals with OCA from the Faroe Islands. The C10orf11 gene was identified using gene mapping of a consanguineous family. In addition, a mutation in the same C10orf11 gene was found in an albino from Lithuania.
These data strongly suggest a role of this new gene in the differentiation of melanocytes. At birth, people with different phenotypic forms of OCA present, in general, white hair and very fair or whitish-pink skin. However, photoprotection conferred by melanin is not total, even in dark-skinned individuals, who also suffer solar radiation-induced DNA damage. This damage generally occurs at a degree that is reversible by the mechanisms of cellular DNA repair, thus reducing the risk of malignant transformation.
By contrast, in fair-skinned individuals with insufficient melanin to provide effective protection against solar radiation, the extent of DNA damage can exceed the repair ability of these mechanisms, with major risk of malignant transformation. Actinic cheilitis: a case report and a review of the literature. Eur J Dent. Oculocutaneous albinism and squamous cell carcinoma of the skin of the head and neck in Sub-Saharan Africa.
J Skin Cancer. Albinos who have little or no skin melanin are therefore highly susceptible to UV-induced cancers. Analysis of MC1R variants in Indian oculocutaneous albinism patients: highlighting the risk of skin cancer among albinos. J Genet. Researchers believe that this protein may also help regulate the relative acidity pH of melanosomes.
Tight control of pH is necessary for most biological processes. More than 80 mutations in the OCA2 gene have been identified in people with oculocutaneous albinism type 2.
People with this form of albinism often have light yellow, blond, or light brown hair; creamy white skin; light-colored eyes; and problems with vision. The most common OCA2 mutation is a large deletion in the gene, which is found in many affected individuals of sub-Saharan African heritage.
Other OCA2 gene mutations, including changes in single DNA building blocks base pairs and small deletions, are more common in other populations. Mutations in the OCA2 gene disrupt the normal production of melanin, which reduces coloring of the hair, skin, and eyes and affects vision.
The OCA2 gene is located in a region of chromosome 15 that is often deleted in individuals with Angelman syndrome. A loss of this gene does not cause the characteristic neurologic features of Angelman syndrome; however, people with this condition who are missing one copy of the OCA2 gene tend to have unusually light-colored hair and fair skin. Cells with only one copy of the OCA2 gene make a reduced amount of P protein compared with cells with two functional copies of this gene, which affects the coloring of the hair and skin.
A small percentage of people with Angelman syndrome also have oculocutaneous albinism type 2. This condition occurs when people have two nonfunctional copies of the OCA2 gene in each cell.
In addition to a deletion in chromosome 15 that removes one copy of the OCA2 gene, these individuals have a mutation in the OCA2 gene on the other copy of chromosome As a result, cells make little or no functional P protein. A lack of P protein disrupts the production of melanin, leading to the characteristic features of albinism.
The region of chromosome 15 containing the OCA2 gene is often deleted in individuals with Prader-Willi syndrome. A loss of this gene does not cause intellectual disability and the other characteristic features of Prader-Willi syndrome; however, people with this condition who are missing one copy of the OCA2 gene tend to have unusually light-colored hair and fair skin.
This mutation, written as SerTer or SX, affects the amino acid serine at protein position Other alterations in this gene have been reported in a few affected people of non-African heritage. Most TYRP1 mutations lead to the production of an abnormally short, nonfunctional version of tyrosinase-related protein 1. Because this enzyme plays a role in normal pigmentation, its loss leads to the changes in skin, hair, and eye coloration that are characteristic of oculocutaneous albinism. Genetics Home Reference has merged with MedlinePlus.
Learn more. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. TYRP1 gene tyrosinase related protein 1. From Genetics Home Reference.
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