Cystic fibrosis (CF) is a genetic disease that is inherited from one’s parents. This section describes how parents can pass a CF gene mutation on to their child. If you have more questions, please talk with your doctor or a genetic counselor.
Every cell in our body contains genetic information, a complete set of instructions for how the body looks, grows, develops and works.
You can think of your genetic information as an encyclopedia with 23 volumes. Each volume contains thousands of entries or topics and is made up of billions of letters. Each of us has a full genetic encyclopedia in every one of our cells. That information is the same, whether the cell is a blood cell, a skin cell or a hair cell.
Each pair is made up of a copy of a chromosome from the mother and the father. Therefore, a child inherits two copies of every “volume” of the encyclopedia, one from each parent.
Genetic information is stored in chromosomes. These are the different volumes of our genetic encyclopedia. Humans have 23 pairs of chromosomes.
Each chromosome is further divided into genes, which are the entries, or topics, in the encyclopedia. The genes supply the body with instructions for making certain proteins. These proteins affect the body’s health, growth and development. Genes also affect our physical looks, like hair and eye color.
All of this genetic information is in code and stored as a chemical called deoxyribonucleic acid (DNA). The DNA code is made up of letters that spell out the entries of our genetic encyclopedia.
If we all shared 100 percent of our genetic material then we would all be as alike as identical twins are. In fact, not every single letter in the genetic encyclopedia is the same in all of us, which helps to explain why we are not all exactly alike.
Changes in the CF Gene
Within our genetic encyclopedia, there are small differences in our genes. Sometimes the differences are minor or do not affect a person’s health. This would be like two encyclopedia entries that are worded in slightly different ways, but still say the same thing and have the same meaning. These differences are called neutral variants. In these cases, people’s genes may differ or the protein made by the gene is slightly different, but they are working right.
At other times, the difference in a gene may cause the protein to not be made or not work. When the genetic difference causes a harmful change, it is called a mutation rather than a variant. CF is caused by mutations in a certain gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The CF gene was discovered in 1989 on chromosome pair 7 — volume 7 in our genetic encyclopedia.
Cystic fibrosis is an example of a recessive disease. That means a person must have a mutation in both copies of the CF gene to have CF. If someone has a mutation in only one copy of the CF gene and the other copy is normal, he or she will not have CF and is a CF carrier. Both parents of a child with cystic fibrosis are CF carriers.
CF carriers each have one CF gene mutation. Parents can pass that mutated copy of the CF gene to their children.
Each time two CF carriers have a child together, there is a 1 in 4 chance that both will pass along their CF mutation to their child. Because the child would get two CF gene mutations, the child would have CF. However, there is a 3 in 4 chance that each child will NOT have CF.
Children of two carriers may be healthy CF carriers like their parents. There is also a 1 in 4 chance that their children will NOT get a CF gene mutation.
In a family with four children, it is possible for none or all of them to have CF. Each baby has the same chance to inherit CF mutations from both parents, no matter whether any of the other siblings are carriers or have CF.
CF Variants and Mutations
All 50 states do conduct newborn screening for cystic fibrosis. If a newborn screening test is positive, the baby should have a sweat chloride test to find out whether or not the baby has CF.
Genetic information also can be used to help diagnose CF by genetic testing. Genetic information and genetic testing can be used to help diagnose CF. It can also be used for genetic counseling and finding CF carriers, but cannot be used to tell you how healthy or sick someone with CF will be.
Sometimes, however, reading a genetic test result, especially on a healthy newborn baby, is not so simple. More than 1,800 different genetic changes (mutations and variants) have been identified in the CF gene.
These genetic changes can be grouped into different types, based on how confident scientists are that the change actually causes the CF disease.
- Confirmed CF-causing mutations. These mutations are seen in people with CF. When a person inherits two of these mutations (one from each parent) that person will always have CF. In laboratory tests, these genetic mutations clearly show that the CFTR protein does not work.
The Cystic Fibrosis Foundation is supporting a project, called CFTR2 , that is collecting information on all confirmed CF-causing mutations. On the CFTR2 website, you will be able to find a CF gene mutation and learn if it causes CF or is a neutral variant. The American College of Medical Genetics (ACMG) has a list of 23 mutations that is used in many carrier screening tests and programs.
- Suspected CF-causing mutations. These are mutations that have been reported in people with CF, but have not been confirmed to always cause CF.
- Variants of uncertain clinical impact. We do not know if these mutations cause CF. They could be further broken down into:
- Mutations that sometimes cause CF, but sometimes do not.
- Mutations that have not been found often enough through genetic testing to know for sure if they do or do not cause CF.
- Mutations linked with having one or more symptoms related with CF. When people who had one or two of the clinical signs of CF (for example, chronic pancreatitis, sinus disease or male infertility) but not full CF disease were examined, certain CF mutations were found. Sometimes these mutations are also seen in people with CF. They can be called CF-related mutations and often overlap with the “variants of uncertain clinical impact” group.
- Neutral variants. These are genetic changes that do not cause CF.
If genetic testing is done for more than the confirmed CF-causing mutations, it is possible to find a change that is not known to be either a neutral variant (i.e., does not cause disease) or a mutation that causes CF. In this case, the person has at least one genetic change that scientists are not certain causes CF. For these people, further testing, such as sweat testing, can be helpful.
It is also sometimes hard to be completely certain whether a person has CF. These people may be told they have CRMS and need to be followed by a CF Foundation-accredited care center over time to see if CF symptoms develop. When a person has signs or symptoms of CF (such as lung infections, weight loss or an inability to gain weight), he or she should be seen at a CF Foundation-accredited CF care center for sweat testing and a full CF evaluation.
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