Genetic Cause of Cutaneous Neurofibromas

NF1 arises from a mutation in the NF1 gene on chromosome 17. In roughly 50% of cases, the mutant form of the gene is inherited from a parent through an autosomal dominant inheritance pattern (which means a single copy of the mutated gene can cause the disease). In the other half of cases, the syndrome results from a new mutation in the NF1 gene that was not inherited from a parent. If that mutation occurs early in the development of the embryo, a person with the new mutation can then pass it on to their children.

Normally, the NF1 gene encodes a protein call neurofibromin. Neurofibromin is widely expressed in almost all tissues, but is most abundant in the brain, spinal cord, and peripheral nervous system. In healthy cells, one of the important functions of neurofibromin is to bind to the protein Ras. Mutations in Ras have been implicated in NF1-associated benign tumors, NF1-associated cancers, and other cancers common to the general population.