Neurofibromatosis type 1 (NF1) is caused by mutations in a specific gene called the NF1 gene, which is located on chromosome 17. This gene is responsible for producing a protein named neurofibromin. Neurofibromin plays a crucial role in regulating cell growth by acting as a negative regulator in a cellular signaling pathway known as the RAS-MAPK pathway. When the NF1 gene is mutated, the production or function of neurofibromin is disrupted, leading to uncontrolled cell growth and the development of tumors along nerves, which are characteristic of NF1.
The NF1 gene mutation can be inherited from a parent in an autosomal dominant pattern, meaning only one copy of the mutated gene is enough to cause the disorder. However, about half of all NF1 cases arise from new mutations that occur spontaneously, without any family history. These spontaneous mutations happen by chance during the formation of reproductive cells or in early embryonic development. People with these new mutations often have milder symptoms compared to those who inherit the mutation.
Because neurofibromin normally helps keep cell growth in check, its loss or malfunction allows cells to grow and divide abnormally, leading to the formation of benign tumors called neurofibromas. These tumors can appear on the skin, nerves, and other parts of the body. The mutation affects not only tumor growth but also other processes in the body, which is why NF1 can cause a wide range of symptoms including skin changes, bone deformities, and learning difficulties.
The NF1 gene mutation is highly variable, meaning different people with NF1 can have different mutations in the gene, which contributes to the wide range of symptoms and severity seen in the disorder. Because the gene mutation affects a key regulatory protein, the consequences extend beyond just tumor formation to impact how cells communicate and grow throughout the body.
In summary, NF1 is caused by mutations in the NF1 gene on chromosome 17, which impair the function of neurofibromin, a protein that normally controls cell growth. These mutations can be inherited or occur spontaneously, leading to abnormal cell growth and the development of tumors and other symptoms associated with neurofibromatosis type 1.
