Carrier Screening

Carrier Screening

You could be carrying a genetic mutation for a debilitating disease such as cystic fibrosis, sickle cell disease or Tay-Sachs disease and not even know it. That's because carriers of these mutations have no symptoms-in fact, they don't even have the disease.

Genes come in matched pairs, except for those on the sex chromosomes. In the case of autosomal recessive disorders such as these, if only one of these matched genes is damaged, there's no problem. The unaffected gene does the job. In fact, a disease-causing mutation can run through dozens of generations of a family without ever making itself known.

But if two carriers of the same gene change have a child, their chance of passing on what genetic counselors sometimes call a "double whammy"-two defective genes-is 25 percent. Of course, their chance of passing on two unaffected genes is also 25 percent, and the chance that a child will be a healthy carrier (with one normal gene and one defective one, but not afflicted with the disease) is 50 percent.

The exception to this pattern occurs if a disorder is recessive and X-linked. The X is the symbol for the larger sex chromosome. A child who inherits two X chromosomes is a girl. A child with an X chromosome and a Y chromosome is a boy. If a mother has a disease-linked recessive mutation on one of her X chromosomes, she is a carrier of the disorder but should have no or minimal symptoms herself. If she has a son, he will have a 50 percent risk of inheriting the disorder because he has no backup X chromosome; a daughter will have a 50 percent chance of being a carrier, like her mother.

Fragile X syndrome, as its name suggests, is one such X-linked disorder. Boys who inherit the mutation usually develop the disease, the most common form of genetically inherited mental retardation. Girls who inherit a fragile X mutation are more likely to be carriers. (The gene is unstable and the mutation tends to increase in size over succeeding generations, so that girls may eventually be affected as well, though the mental retardation is not usually as severe as it is in boys.) All affected individuals are related through females, as the fragile X gene "grows" only in the egg. If you have a family history of mental retardation, testing can determine whether a fragile X mutation is responsible and whether you are a carrier.

As with other types of testing, genetic counseling can help you understand carrier screenings. A counselor can also help you develop strategies for sharing the information with other family members who may also be at risk of carrying the mutation.

Carrier screening is recommended for any disorder that has surfaced in your family, either by virtue of a relative developing the disease or testing positive as a carrier. However, you should also consider screening for mutations found frequently in your particular ethnic group. The prevalence of genetic disorders is linked closely to ethnic heritage. Caucasians, for example, have a much higher risk than most other groups for cystic fibrosis, and those of African American descent are more likely to be carriers of sickle cell anemia mutations.

Many carrier screening tests are relatively inexpensive (usually $50 to $75 per individual screen) because they don't require sequencing of an entire gene. Instead they zero in on mutations known to be common in particular groups. The results are generally very accurate (95 percent or higher) and straightforward: A person is either a carrier or not.

Below is a list linking various groups to genetic disorders they are more likely to inherit:

• Caucasians: phenylketonuria, hemochromatosis, cystic fibrosis, alpha 1-antitrypsin deficiency, celiac disease (no genetic test available, but physicians can test blood to measure levels of antibodies to gluten. These antibodies are antigliadin, anti-endomysium, and antireticulin.)
• African Americans: sickle cell disease and Thalassemia
• East Asians (except Koreans): Thalassemia
• Irish, French Canadians and Cajuns: Tay-Sachs disease
• Mediterraneans: thalassemia, celiac disease, and familial Mediterranean fever
• Southeast Asians (Cambodians, Laotians and Vietnamese): hemoglobinopathies (disorders of hemoglobin, the oxygen-carrying component of red blood cells)

There is also a battery of tests for mutations found more often in the Ashkenazi Jewish population. The Ashkenazi are Jews of Central and East European descent, and they account for some 80 percent of the Jewish population in the United States.

The carrier screening tests for Ashkenazi Jews varies from program to program. Some test only for Tay-Sachs and Canavan diseases; some include many other disorders, such as Gaucher disease, Bloom syndrome, Fanconi anemia, Niemann-Pick disease and hereditary deafness. If you use insurance to pay for testing, you may have to use a particular center and test panel. Testing for Familial Dysautonomia is now available, too.

Many panels also include a screen for cystic fibrosis (CF). This condition is not more common in the Ashkenazi population. Caucasians are actually more likely to carry CF mutations than other groups. Still, the ratio of the Ashkenazi population that carries known CF mutations is fairly high, about one in 29. Three specific mutations are common in this population, making testing more specific.

People of Ashkenazi Jewish origin are, of course, no more likely to have a genetic disorder than other populations; they have been the focus of much genetics research because the population remained relatively isolated and small for centuries.

Experts Recommend Preconception Screening

You might think that if you and your partner come from different backgrounds, carrier screening is unnecessary. The American College of Obstetricians and Gynecologists, however, advises that if one partner in a couple is at high risk and the other is not, the high-risk partner should be screened. If that person tests positive as a carrier the other partner should be screened.

Genetics experts recommend carrier screening in young adulthood or before a marriage-and definitely before a couple tries to conceive. But you may have to be proactive in seeking the testing. If you live in a region where there aren't many members of your ethnic group, a local physician may not be well informed about the issues.

If two prospective parents are found to be carriers of a disease, their options include:

• Adoption
• use of donor sperm or a donor egg
• in vitro fertilization and preimplantation genetic testing of the embryos (an expensive process)
• prenatal testing (with the option of an abortion if the fetus has two copies of a debilitating mutation)

For some diseases, the outcome of having two mutated genes is variable from patient to patient. Someone with a particular disease mutation, for example, may not have symptoms until middle age, or may go a lifetime asymptomatic, making decisions about testing-and what to do if a fetus turns out to be affected-difficult for prospective parents.