NF1 loss of heterozygosity (LOH) in the Schwann cell lineage leads to neurofibroma development, NF1−/− melanocytes lead to café-au-lait macules and Lisch nodules, NF1−/− osteoblasts lead to pseudoarthrosis of the tibia, and NF1−/− in glial cells leads to astrocytomas. This evidence concerns the gene NF1 and Cafe-au-lait spot.