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Copyright 2008, 2012
NORD is very grateful to William S. Oetting, PhD, School of Pharmacy, Experimental and Clinical Pharmacology and Institute of Human Genetics, University of Minnesota, for assistance in the preparation of this report.
Ocular albinism type 1 (OA1), or X-linked ocular albinism, is the most common form of ocular albinism. Ocular albinism is a genetic disorder characterized by vision abnormalities in affected males. Vision deficits are present at birth and do not become more severe over time. Affected individuals have normal skin and hair pigmentation. Ocular albinism is inherited as an X-linked recessive genetic condition and caused by mutations in the G protein-coupled receptor 143 (GPR143) gene.
Ocular albinism primarily affects the eyes. Several vision problems can occur with ocular albinism including an involuntary movement of eyes back and forth (nystagmus), reduced iris pigment in some individuals, reduced retinal pigment, lack of development of the fovea (foveal hypoplasia) leading to blurred vision, and abnormal connections in the nerves from the retina to the brain that prevents the eyes from tracking together and reduces depth perception. Crossed eyes (strabismus) and sensitivity to light are also common. Typically individuals have normal hair and skin pigmentation.
Congenital motor nystagmus is a genetic condition characterized by an involuntary movement of eyes back and forth (nystagmus). Affected individuals will often turn or bob their head to try to improve vision clarity. Pigmentation in the eye is normal. There is preliminary evidence that some mutations of GPR143 result in X-linked congenital nystagmus in males. This has been seen in several different Chinese families. Affected males have congenital nystagmus but they do not have the additional changes typically seen in individuals with classical X-linked ocular albinism including a reduction in retinal pigmentation and pathological changes to the fundus. Female carriers appear to be unaffected. Further research needs to be done to understand how mutations in the same gene can result in different outcomes.
Mutations in the G protein-coupled receptor 143 (GPR143) gene on the X chromosome cause ocular albinism type 1 (OA1). This protein is found in the retinal pigment epithelium of the eye and is thought to be involved in signaling within the pigment cell to regulate melanin pigment production. This protein also interacts with the premelanosomal protein MART1 which also is part of the regulation of melanin pigment formation. Mutations in GPR143 result in a decrease in melanin pigment production and enlarged aberrant premelanosomes which is the intracellular location of pigment production in the pigment cell.
Ocular albinism is inherited as an X-linked recessive genetic condition. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and most of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because inactivation of the X chromosome is random and usually half of the cells in the eye have the normal X chromosome activated resulting in normal vision. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
The prevalence of ocular albinism has been reported to be one male in 20,000 births.
Symptoms of the following disorders can be similar to those of ocular albinism. Comparisons may be useful for a differential diagnosis:
Oculocutaneous albinism is a group of rare inherited disorders characterized by a reduced amount or complete lack of color (pigmentation) in the skin, hair, and eyes. These conditions are caused by mutations in specific genes that are necessary for the production of melanin pigment. Abnormal or insufficient melanin pigment results in vision abnormalities and light skin that is very susceptible to damage from the sun. In some cases, individuals with oculocutaneous albinism can have near normal skin and hair pigmentation as seen in ocular albinism, making it appear to be X-linked ocular albinism, but these individuals are usually born with reduced skin and hair pigmentation and accumulate pigment with time unlike individuals with ocular albinism who are born with normal skin and hair pigmentation. Oculocutaneous albinism is inherited as an autosomal recessive genetic condition. (For more information on this disorder, choose "oculocutaneous albinism" as your search term in the Rare Disease Database.)
Ocular albinism with sensorineural deafness is a condition that includes the vision abnormalities of ocular albinism as well as deafness and balance problems. Some affected individuals have different colored eyes and a white forelock of hair. Ocular albinism with sensorineural deafness is inherited as an autosomal dominant genetic condition. This is also termed Waardenburg syndrome.
The diagnosis of ocular albinism is based on the characteristic eye findings. Female relatives who carry the gene for ocular albinism will have retinal pigment abnormalities. Molecular genetic testing for GPR143 gene detects mutations in approximately 90% of affected males and is available to confirm the diagnosis.
Individuals diagnosed with ocular albinism should be evaluated by an ophthalmologist at the time of diagnosis to determine the extent of the disease and have ongoing ophthalmologic examinations annually. Glasses or contact lenses can greatly improve vision. Dark glasses or a hat with a brim can help to reduce sun sensitivity.
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For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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King RA, Hearing VJ, Creel DJ, et al. Albinism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Basis of Inherited Disease. New York, NY: McGraw-Hill; 2001:5587-627.
King RA, Oetting WS, Summers CG, et al. Abnormalities of pigmentation. In: Rimoin DL, Connor JM, Pyritz RE, Korf BR (eds) Emery and Rimoin's Principles and Practice of Medical Genetics, 4th ed. London: Harcourt; 2001.
Hu J, Liang D, Xue J, Liu J, Wu L. A novel GPR143 splicing mutation in a Chinese family with X-linked congenital nystagmus. Mol Vis. 2011;17:715-22.
Peng Y, Meng Y, Wang Z, et al. A novel GPR143 duplication mutation in a Chinese family with X-linked congenital nystagmus. Molec. Vis. 2009;15:810-814.
Camand O, Boutboul S, Arbogast L, et al. Mutational analysis of the OA1 gene in ocular albinism. Opthalmic Genet. 2003;24:167-73.
Oetting WS. New Insights into ocular albinism type 1 (OA1): Mutations and polymorphisms of the OA1 gene. Hum Mutat. 2002;19:85-92.
Bassi MT, Bergen AA, Bitoun P, et al. Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America. Hum Genet. 2001;108:51-4.
Charles SJ, Green JS, Grant JW, et al. Clinical features of affected males with X-linked ocular albinism. Br J Opthalmol. 1993;77:222-7.
Lewis RA. (Updated April 5, 2011). Ocular Albinism, X-linked. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at http://www.genetests.org. Accessed April 24, 2012.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Albinism, Ocular, Type 1; OA1. Entry No: 300500. Last Edited June 16, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/.Accessed April 24, 2012.
Report last updated: 2012/04/25 00:00:00 GMT+0