chapter  5
Genetics of NF1 and NF2
WithMargaret R. Wallace, Mia MacCollin
Pages 19

This chapter briefly summarizes the clinical and pathological findings of neurofibromatosis 1 (NF1). Together, NF1 and neurofibromatosis 2 (NF2) represent the vast majority of the neurofibromatoses. The first discovered alternatively spliced NF1 exon is 23a, which encodes a 21-amino sequence that is conserved across species. The presence of 23a results in slightly decreased GTPase-activating protein (GAP) activity, although this isoform has higher affinity for ras-GTP. The hallmark feature of NF1 is the neurofibroma a benign Schwann cell tumor which arises along peripheral nerves. Only a handful of putative mutations of the NF2 gene have been found in malignant melanoma, breast adenocarcinoma and colon cancer and none have been seen in ovarian carcinoma, or hepatocellular carcinoma. A number of functional and genetic studies have firmly concluded that NF1 is a tumor suppressor gene, following the cancer syndrome paradigm presented by A. J. Knudson, that tumors contain one constitutionally inactivated allele, with the other allele subsequently inactivated via somatic mutation.