Oculocutaneous albinism type I

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Oculocutaneous albinism type I
Other namesOCA1A or OCAIA
Symptoms Decreased or absent pigmentation of the hair, skin, and eyes.
Usual onsetIs inherited and phenotypically present beginning at birth
TypesOCA 1-7
CausesMutation in the TYR gene on chromosome 11
TreatmentNo currently known treatment
FrequencyAutosomal Recessive Pattern, 1/20,000 people in world

Oculocutaneous albinism type I or type 1A [1] is form of the autosomal recessive condition oculocutaneous albinism that is caused by a dysfunction in the gene for tyrosinase (symbol TYR or OCA1).

Contents

The location of OCA1 may be written as "11q1.4–q2.1", meaning it is on chromosome 11, long arm, somewhere in the range of band 1, sub-band 4, and band 2, sub-band 1. Since the disorder is autosomal recessive, genetic counseling can be used to determine if both parents are heterozygous for the condition when considering having children. If both parents are heterozygous, their child has a 25% chance of inheriting both recessive copies of OCA1 and having the condition. [2]

OCA1 is defined by an absence of pigmentation throughout the body, including the eyes, hair, and skin. This rare condition is found in 1 out of 20,000 people around the world, being much more prevalent in Caucasians. [3] Whilst there is no known cure for the condition, there are established ways to manage life with OCA1, including safety in the sun, and regular checks for skin diseases such as skin cancer.

Signs and symptoms

OCA is characterized by the absence of pigmentation caused by the mutation that effects the production of tyrosinase that causes partial or total absence of melanin in the hair, skin, and eyes. [4] Reduction in melanin production specifically in the peripheral retina during embryonic development can trigger other symptoms such as abnormal nerve fiber projection that causes defects in neuronal migration that interrupts visual pathways and creates reduced visual acuity in the range of 20/60 to 20/400. [4] This vision acuity is dependent upon the amount of pigmentation in the eye. Acuity is usually better in individuals with greater amounts of pigment. [5] Aside from decreased pigment in the iris and retina, optic changes include decreased visual acuity, misrouting of the optic nerves at the chiasm, and nystagmus. [1]

OCA1 is the most severe form of albinism, in which the unpigmented iris is translucent and the eye appears blue or mauve in ambient light, pink or red in bright light, and in which the skin has no pigmentation at all (unlike other forms of albinism, in which there is some residual pigmentation). [6] OCA1 is caused by mutations in the TYR gene, where there is a complete lack of tyrosinase activity. [1]

Genetics

The tyrosinase (TYR) gene is located on chromosome 11q14. This protein coding gene produces tyrosinase, an enzyme which catalyzes a total of three steps in the conversion of tyrosine to the end product, melanin. [7] This enzyme and conversion process takes place within melanocytes, which are specialized cells for melanin production. [8] Melanin is a large group of molecules that give skin, eyes, and hair their respective colors. It is also partially responsible for vision, as it protects the light sensitive portion of the eye, the retina, through absorbing light. [8] OCA Type 1A is an autosomal recessive condition, meaning there is a homozygous or compound heterozygous mutation related to the TYR gene. [1] There are many different types of albinism, differing due to the effects of various mutations. Oculocutaneous albinism type IA is the most severe type of albinism, as it is characterized by no melanin production. [9] Other types of albinism have limited melanin production. Because type IA Albinism has no functioning copies of the gene, it is the most severe type of albinism. The mutations on this gene lead to a complete lack of tyrosinase activity as the inactive enzyme is produced. [1] An inactive enzyme can be caused by a missense or nonsense mutation. Due to the lack of enzymes needed to catalyze the production of melanin, patients do not have melanin protecting them from the sun, resulting in sensitive eyes, skin, and other symptoms mentioned in the signs and symptoms of OCA1A. The different forms of albinism and range of severity is dependent upon the level of melanin production, which depends on the level of tyrosinase activity.[ citation needed ]

Diagnosis

Because albinism is autosomal recessive, prenatal genetic screening and genetic counseling can be performed to diagnose OCA early on. When pathogenic variants are known to be present in an affected family, carrier testing can also be conducted. [2] The level of expression can be variable depending on the pigmentation background, so phenotypically, OCA can be expressed on a spectrum. [4] OCA is heterogenous, with OCA1 being caused by a mutation in the TYR gene. [2] The separate subdivisions are categorized by the genes that they effect. [10] The seven types are not evenly distributed amongst ethnic groups with OCA1 being the subtype most prominent in Caucasians - "accounting for approximately 50% of cases worldwide." [10] [3] [11]

Previously, diagnosis was done from observation of hypopigmentation which is obvious at birth, but this is now insufficient early on to distinguish between the seven major types of OCA. [2]

Prenatal testing has been achieved through fetal skin biopsy followed by subsequent histologic and electron microscope examination for melanin levels. [12] Clinical findings have established that molecular genetic testing of TYR, [12] the gene encoding tyrosinase, can distinguish between 1A and 1B because the phenotypes can be identical during the first year of life. [2] OCA1A results in complete loss of tyrosinase enzyme activity. [4] Individuals with 1B will experience increased pigmentation with age because they have a very low level of melanin production that can increase. [2] The histological approach for prenatal diagnosis is useful for all families at risk for OCA1 whereas the molecular genetic test is only helpful when at least one mutation is known. [12]

Management

There is currently no treatment for this disease. [4] [13] The extremely hypopigmented skin that is characteristic in OCA1 particularly leads to risk of skin damage and non-melanotic skin cancers due to increased sensitivity to UV rays. [4] In OCA1B, because there is some presence of melanin, it grows with age and pigmentation can increase; the same cannot be said for OCA1A. [4] Individuals affected by OCA1A should be attentive to the amount of sun exposure they experience and wear proper protection such as clothing that covers the skin. [4] [5] Additionally, individuals may need corrective visual aids for their visual acuity of 1/10 or less with intense photophobia. [4] Visual aids can both improve vision or protect eyes from bright lights. [5] These visual aids can be adjusted for based on individual needs.[ citation needed ]

Individuals should receive annual skin evaluation to access for damage or skin cancers that can be induced from sun exposure. [5] In some situations, therapy or surgery can correct crossed eyes (strabismus) or rapid eye movements (nystagmus). [5]

Epidemiology

The highest frequency of Albinism type IA is in Northern Ireland, with a phenotype frequency of around 1: 10,000. [1] First cousin - marriages accounted for 4.5% of the parents of patients. [1] Additionally, symptoms that could be heterozygous mutations, such as abnormal iris translucency occurred in 70% of the parents and children of individuals affected with this condition. [1] In general, the phenotypical appearance of OCA1A is associated with northern and western Europe. [14] This is because over 50% of OCA1 subjects are Caucasians. [14] OCA1 is also the most common form of Albinism in China and Japan. [14] The overall frequency is 1: 20,000 people in the world. [14]

Related Research Articles

<span class="mw-page-title-main">Albinism in humans</span> Condition characterized by absence of pigment

Albinism is a congenital condition characterized in humans by the partial or complete absence of pigment in the skin, hair and eyes. Albinism is associated with a number of vision defects, such as photophobia, nystagmus, and amblyopia. Lack of skin pigmentation makes for more susceptibility to sunburn and skin cancers. In rare cases such as Chédiak–Higashi syndrome, albinism may be associated with deficiencies in the transportation of melanin granules. This also affects essential granules present in immune cells, leading to increased susceptibility to infection.

<span class="mw-page-title-main">Melanin</span> Group of natural pigments found in most organisms

Melanin is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes.

<span class="mw-page-title-main">Melanocyte</span> Melanin-producing cells of the skin

Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer of the skin's epidermis, the middle layer of the eye, the inner ear, vaginal epithelium, meninges, bones, and heart found in many mammals and birds. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system.

<span class="mw-page-title-main">Tiger eye</span> Color of horses eyes

Tiger eye or goat eye is a gene causing diluted eye color in horses. There are two variants, Tiger-eye 1 (TE1) and Tiger-eye 2 (TE2), which are both recessive. Horses displaying tiger eye typically have a yellow, orange, or amber iris. Tiger eye has only been found in Puerto Rican Paso Fino horses. Horses of related breeds were tested, and none were found to have either tiger eye allele. No obvious link between eye shade and coat color was seen, making this the first studied gene in horses to affect eye color but not coat color. Tiger eye does not appear to affect vision, and there were no signs of reduced pigment on the retina or retinal pigment epithelium.

<span class="mw-page-title-main">Cat coat genetics</span> Genetics responsible for the appearance of a cats fur

Cat coat genetics determine the coloration, pattern, length, and texture of feline fur. The variations among cat coats are physical properties and should not be confused with cat breeds. A cat may display the coat of a certain breed without actually being that breed. For example, a Neva Masquerade could wear point coloration, the stereotypical coat of a Siamese.

<span class="mw-page-title-main">Eye color</span> Polygenic phenotypic characteristic

Eye color is a polygenic phenotypic trait determined by two factors: the pigmentation of the eye's iris and the frequency-dependence of the scattering of light by the turbid medium in the stroma of the iris.

<span class="mw-page-title-main">Plumage</span> Layer of feathers that covers a bird

Plumage is a layer of feathers that covers a bird and the pattern, colour, and arrangement of those feathers. The pattern and colours of plumage differ between species and subspecies and may vary with age classes. Within species, there can be different colour morphs. The placement of feathers on a bird is not haphazard but rather emerges in organized, overlapping rows and groups, and these feather tracts are known by standardized names.

<span class="mw-page-title-main">Tyrosinase</span> Enzyme for controlling the production of melanin

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper–Mason pathway. Firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation. It is found inside melanosomes which are synthesized in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR gene.

<span class="mw-page-title-main">Hermansky–Pudlak syndrome</span> Medical condition

Heřmanský–Pudlák syndrome is an extremely rare autosomal recessive disorder which results in oculocutaneous albinism, bleeding problems due to a platelet abnormality, and storage of an abnormal fat-protein compound. It is thought to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800. Many of the clinical research studies on the disease have been conducted in Puerto Rico.

Oculocutaneous albinism is a form of albinism involving the eyes, the skin, and the hair. Overall, an estimated 1 in 20,000 people worldwide are born with oculocutaneous albinism. OCA is caused by mutations in several genes that control the synthesis of melanin within the melanocytes. Seven types of oculocutaneous albinism have been described, all caused by a disruption of melanin synthesis and all autosomal recessive disorders. Oculocutaneous albinism is also found in non-human animals.

<span class="mw-page-title-main">White horse</span> Horse coat color

A white horse is born predominantly white and stays white throughout its life. A white horse has mostly pink skin under its hair coat, and may have brown, blue, or hazel eyes. "True white" horses, especially those that carry one of the dominant white (W) genes, are rare. Most horses that are commonly referred to as "white" are actually "gray" horses whose hair coats are completely white. Gray horses may be born of any color and their hairs gradually turn white as time goes by and take on a white appearance. Nearly all gray horses have dark skin, except under any white markings present at birth. Skin color is the most common method for an observer to distinguish between mature white and gray horses.

<span class="mw-page-title-main">P protein</span> Protein-coding gene in humans

P protein, also known as melanocyte-specific transporter protein or pink-eyed dilution protein homolog, is a protein that in humans is encoded by the oculocutaneous albinism II (OCA2) gene. The P protein is believed to be an integral membrane protein involved in small molecule transport, specifically of tyrosine—a precursor of melanin. Certain mutations in OCA2 result in type 2 oculocutaneous albinism. OCA2 encodes the human homologue of the mouse p gene.

<span class="mw-page-title-main">Membrane-associated transporter protein</span> Protein

Membrane-associated transporter protein (MATP), also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1, is a protein that in humans is encoded by the SLC45A2 gene.

Ocular albinism is a form of albinism which, in contrast to oculocutaneous albinism, presents primarily in the eyes. There are multiple forms of ocular albinism, which are clinically similar.

<span class="mw-page-title-main">Ocular albinism type 1</span> Most common type of ocular albinism

Ocular albinism type 1(OA1) is the most common type of ocular albinism, with a prevalence rate of 1:50,000. It is an inheritable classical Mendelian type X-linked recessive disorder wherein the retinal pigment epithelium lacks pigment while hair and skin appear normal. Since it is usually an X-linked disorder, it occurs mostly in males, while females are carriers unless they are homozygous. About 60 missense and nonsense mutations, insertions, and deletions have been identified in Oa1. Mutations in OA1 have been linked to defective glycosylation and thus improper intracellular transportation.

<span class="mw-page-title-main">Acromelanism</span> Coloration of animal coat/fur

Acromelanism is a genetic condition that results in pigmentation being affected by temperature. It results in point coloration where the extremities of an animal are a different colour to the rest of the body. It is commonly known for the coloration of Siamese and related breeds of cat, but can be found in many other species including dogs, rabbits, rats, mice, guinea pigs, minks, and gerbils. It is a specific type of point coloration.

<span class="mw-page-title-main">Amelanism</span> Pigmentation abnormality

Amelanism is a pigmentation abnormality characterized by the lack of pigments called melanins, commonly associated with a genetic loss of tyrosinase function. Amelanism can affect fish, amphibians, reptiles, birds, and mammals including humans. The appearance of an amelanistic animal depends on the remaining non-melanin pigments. The opposite of amelanism is melanism, a higher percentage of melanin.

<span class="mw-page-title-main">Solid white (chicken plumage)</span> Breed of chicken

In poultry standards, solid white is coloration of plumage in chickens characterized by a uniform pure white color across all feathers, which is not generally associated with depigmentation in any other part of the body.

<span class="mw-page-title-main">Albinism</span> Disorder causing lack of pigmentation

Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and reddish pink or blue eyes. Individuals with the condition are referred to as albinos.

Ocular albinism late onset sensorineural deafness (OASD) is a rare, X-linked recessive disease characterized by intense visual impairments, reduced retinal pigments, translucent pale-blue irises and moderately severe hearing loss from adolescence to middle-age. It is a subtype of Ocular Albinism (OA) that is linked to Ocular albinism type I (OA1). OA1 is the most common form of ocular albinism, affecting at least 1/60,000 males.

References

  1. 1 2 3 4 5 6 7 8 Online Mendelian Inheritance in Man (OMIM): 203100
  2. 1 2 3 4 5 6 Lewis RA (1993). "Oculocutaneous Albinism Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY". In Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Mirzaa G, Amemiya A, Lewis RA (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID   20301345.
  3. 1 2 Hutton, Saunie M.; Spritz, Richard A. (October 2008). "Comprehensive Analysis of Oculocutaneous Albinism among Non-Hispanic Caucasians Shows that OCA1 Is the Most Prevalent OCA Type". Journal of Investigative Dermatology. 128 (10): 2442–2450. doi:10.1038/jid.2008.109. PMC   3515683 . PMID   18463683.
  4. 1 2 3 4 5 6 7 8 9 "Oculocutaneous Albinism". atlasgeneticsoncology.org. Retrieved 2021-04-26.
  5. 1 2 3 4 5 "Oculocutaneous albinism | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2021-04-26.
  6. ↑ Grønskov, K.; Ek, J.; Brondum-Nielsen, K. (2007). "Oculocutaneous albinism". Orphanet Journal of Rare Diseases. 2. National Center for Biotechnology Information: 43. doi: 10.1186/1750-1172-2-43 . PMC   2211462 . PMID   17980020.
  7. ↑ "OMIM Entry - * 606933 - TYROSINASE; TYR". www.omim.org. Retrieved 2021-04-26.
  8. 1 2 "TYR gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-04-26.
  9. ↑ Ghodsinejad Kalahroudi V, Kamalidehghan B, Arasteh Kani A, Aryani O, Tondar M, Ahmadipour F, et al. (2014-09-12). "Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1)". PLOS ONE. 9 (9): e106656. Bibcode:2014PLoSO...9j6656G. doi: 10.1371/journal.pone.0106656 . PMC   4162572 . PMID   25216246.
  10. 1 2 Yang, Qi; Yi, Sheng; Li, Mengting; Xie, Bobo; Luo, Jinsi; Wang, Jin; Rong, Xiuliang; Zhang, Qinle; Qin, Zailong; Hang, Limei; Feng, Shihan (2019-06-13). "Genetic analyses of oculocutaneous albinism types 1 and 2 with four novel mutations". BMC Medical Genetics. 20 (1): 106. doi: 10.1186/s12881-019-0842-7 . ISSN   1471-2350. PMC   6567650 . PMID   31196117.
  11. ↑ Rooryck, Caroline; Morice-Picard, Fanny; Elçioglu, Nursel H.; Lacombe, Didier; Taieb, Alain; Arveiler, Benoît (October 2008). "Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes and practical aspects: Letter to the Editor". Pigment Cell & Melanoma Research. 21 (5): 583–587. doi:10.1111/j.1755-148X.2008.00496.x. PMID   18821858. S2CID   11728943.
  12. 1 2 3 Rosenmann E, Rosenmann A, Ne'eman Z, Lewin A, Bejarano-Achache I, Blumenfeld A (September 1999). "Prenatal diagnosis of oculocutaneous albinism type I: review and personal experience". Pediatric and Developmental Pathology. 2 (5): 404–14. doi:10.1007/s100249900143. PMID   10441617. S2CID   23369377.
  13. ↑ "Albinism, Oculocutaneous, Type I | Hereditary Ocular Diseases". disorders.eyes.arizona.edu. Retrieved 2021-04-26.
  14. 1 2 3 4 Marçon, Carolina Reato; Maia, Marcus (2019). "Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors". Anais Brasileiros de Dermatologia. 94 (5): 503–520. doi:10.1016/j.abd.2019.09.023. ISSN   0365-0596. PMC   6857599 . PMID   31777350.
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