To understand how these genes can cause albinism, let us review how the products of these genes, which are proteins, help melanin-producing cells called melanocytes make pigment Figure 2A. Enzymes are a special type of protein that help to make chemical reactions happen. Enzymes are responsible for changing the starting material, called tyrosine , into melanin.
The way that the enzymes change the tyrosine is what causes the formation of eumelanin vs. In normal pigmentation, the ratio of eumelanin brown—black pigment to pheomelanin yellow—red pigment is what causes differences in skin color.
In albinism, melanocytes are no longer able to make eumelanin at the proper levels, resulting in formation of more or only pheomelanin Figure 2B. There are seven types of OCA caused by different genes [ 3 ]. Individuals with albinism often experience eye problems. This means that the eyes of individuals with albinism are easily damaged by UV radiation from the sun.
They often experience premature glaucoma, general vision issues, and potential blindness. Albinism can also impair vision, resulting in nearsightedness, farsightedness, or astigmatism, which is blurry vision due to an uneven cornea.
Individuals with albinism are at a higher risk of developing skin cancers and sunburns due to increased sensitivity to the sun. The more damage caused by UV radiation, the higher the chance of getting skin cancer. UV radiation contributes to the formation of skin cancer by generating substances called free radicals, which cause DNA damage in the skin. Pheomelanin actually causes the creation of more free radicals. Therefore, the development of skin cancer in individuals with albinism is due to both reduced protection against sun damage and the increased production of free radicals [ 4 ].
Different types of albinism come with different risks of developing skin damage and skin cancers. For example, skin cancers are a leading cause of death in certain ethnic groups, such as African albinos. Skin cancers can be prevented by protecting the skin with sunscreen and clothing and by early skin checks [ 5 ].
Skin cancers that are detected at a later stage are more difficult to treat, which is why prevention of sun damage and skin checks are so important.
One way that doctors help kids with albinism is by encouraging protection of the skin from the sun. It is crucial that doctors closely monitor children with albinism so that they can detect skin cancers early if they occur [ 1 ]. Doctors can also help kids with albinism by treating eye abnormalities.
Kids with albinism should have an eye examination by the age of 4 months. Within their first 2 years, eye exams are recommended every 3—4 months, which is reduced to every 6 months between ages 2 and 4 and to once a year by the age of 5. HPS is a less common form of albinism but should be suspected if a person with albinism shows unusual bruising or bleeding or if a genetic test for a type of OCA produces inconclusive results. Autosomes are the 22 pairs of chromosomes that contain genes for our general body characteristics, compared to the one pair of sex chromosomes.
We normally have two copies of these chromosomes and the many genes on them — one inherited from our father, the other inherited from our mother. That means that most types of albinism result from inheriting an albinism trait from both the mother and the father who often have typical pigmentation.
In this case, the mother and father are considered to be carriers of the albinism trait because they each carry a recessive gene for the condition but do not manifest the condition themselves. When both parents carry the albinism gene and neither parent has albinism there is a one in four chance at each pregnancy that the baby will be born with albinism.
Ocular albinism OA1 is caused by a change in the GPR gene that plays a signaling role that is especially important to pigmentation in the eye. OA1 follows a simpler pattern of inheritance because the gene for OA1 is on the X chromosome. Females have two copies of the X chromosome while males have only one copy and a Y chromosome that makes them male. To have ocular albinism, a male only needs to inherit one changed copy of the gene for ocular albinism from his carrier mother.
Therefore almost all of the people with OA1 are males. Parents should be suspicious if a female child is said to have ocular albinism. While possible if the mother is a carrier of ocular albinism and the father has ocular albinism, it is extremely rare. For couples who have not had a child with albinism, there is no simple test to determine whether a person carries a gene for albinism. Researchers have analyzed the DNA of many people with albinism and found the changes that cause albinism, but these changes are not always in exactly the same place, even for a given type of albinism.
Moreover, many of the tests do not find all possible changes. Therefore, the tests for the albinism gene may be inconclusive. If parents have had a child with albinism previously, and if that affected child has had a confirmed diagnosis by DNA analysis, there is a way to test in subsequent pregnancies to see if the fetus has albinism.
The test uses either amniocentesis placing a needle into the uterus to draw off fluid or chorionic villous sampling CVS. Cells in the fluid are examined to see if they have an albinism gene from each parent. For specific information and genetic testing, seek the advice of a qualified geneticist or genetic counselor.
Those considering prenatal testing should be made aware that people with albinism usually adapt quite well to their disabilities and lead very fulfilling lives. Eye problems in albinism result from the abnormal development of the eye because of a lack of pigment and often include:.
The iris, the colored area in the center of the eye, has very little or no pigment to screen out stray light coming into the eye. Light normally enters the eye only through the pupil, the dark opening in the center of the iris, but in albinism light can pass through the iris as well. For the most part, treatment consists of visual rehabilitation. Surgery to correct strabismus may improve the appearance of the eyes. But to truly understand the role of OCA2 and the VI mutation in albinism, the researchers needed to look directly at melanosomes.
They were able to turn to helpful colleagues. Co-author Michael Marks at the University of Pennsylvania introduced them to a line of mutant mouse skin cells that had unusually large melanosomes. Anita Zimmerman, professor of medical science who works down the hall at Brown University, tipped them off that bullfrogs happen to have especially large melanosomes in their retinas.
Patch clamp experiments with those large melanosomes confirmed the role of the VI mutation in the failure of chloride ion channels. First, they compared chloride currents in normal melanosomes and ones in which they used interference RNA a method of blocking gene expression targeted to prevent OCA2 production. They found that the melanosomes without OCA2 produced much less current and much less melanin.
Skip to main content. November 21, Brown biology, engineering professors named AAAS fellows.
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