Understanding the NF1 Mutation

Neurofibromatosis type 1 (NF1) is a hereditary disorder caused by an alteration – called a mutation – in the NF1 gene, which is located on chromosome 17. The NF1 gene contains a code of instructions for making a protein called neurofibromin, which is produced in many cells, including nerve cells and specialized cells surrounding nerves (Schwann cells). The neurofibromin protein acts as a tumor suppressor, preventing cells from growing and dividing too rapidly. The NF1 gene mutation leads to the production of a nonfunctional or absent neurofibromin protein that is unable to regulate cell growth and division, resulting in the growth of neurofibromas (skin tumors) along nerves throughout the body.

Inherited Mutations

All people have two copies of every gene – one copy inherited from each parent. The NF1 gene mutation is dominant, which means that only one of the two copies of the gene needs to have the mutation to produce the disorder. A parent with NF1 has a 50% chance of passing the abnormal gene copy to a child. A child who inherits the altered gene will also have the disorder.

Spontaneous Mutations

While half of the cases of NF1 are inherited from a parent, 50% of children diagnosed with NF1 appear to be the first members of their family to have the disorder. In such cases, the genetic alteration, or mutation, occurred in the sperm or egg cell that formed the child. This is called a spontaneous, or new, mutation. A person with a spontaneous mutation of the NF1 gene has a 50% chance of passing the abnormal gene copy to a child.

Determining the Source of the NF Mutation

It’s important to determine whether the disorder is inherited or is the result of a spontaneous mutation, since an individual with an NF1 mutation has a 50% chance of passing on the disorder every time he or she has a child. One way to accomplish this is by means of a thorough examination of each parent whose child has been diagnosed with NF1 to determine the presence of café-au-lait spots or Lisch nodules in the iris of the eyes. If neither parent is found to have signs of NF1, the child’s disorder is most likely the result of a spontaneous, or new, mutation.

Genetic testing is also currently available to confirm the presence of the NF1 gene mutation with 95% sensitivity and may be appropriate in some cases. Some people have features of NF1 that are limited to only one part or one side of their body. This is called mosaic NF1 (also called segmental NF1). Mosaic NF1 is caused by a gene mutation that has arisen after conception, during early development of the person as an embryo. Genetic testing for people with type of NF, while possible, can be more complex than for individuals who do not have this form of the disorder.

What Causes the NF1 Mutation?

In cases where a child’s NF1 is determined to be the result of a spontaneous mutation, parents often wonder if they did something to cause the mutation, such as exposing their child to radiation, medications, alcohol, or other substances in the environment. It’s important to understand that the specific cause of the NF1 gene mutation is currently unknown, and no environmental exposure has been implicated. It’s also important to know that genetic mutations are not uncommon. Cells in the body are continuously dividing, and each time they do, a massive volume of genetic information must be copied correctly. Random errors inevitably occur in the copying process and may be the cause of mutations leading to NF1.

For more information, please contact the UAB Neurofibromatosis Program at 205-934-4983.