Mutational Analysis of the NF1 Gene in Two Families with Neurofibromatosis 1 Accompanied by Pheochromocytoma

* These authors contributed equally to this work. Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant inherited disorders affecting the nervous sys-tem. NF1 is associated with mutations in the NF1 gene, which is located on chromosome sub-band 17q11.2 and contains 57 exons spanning approximately 300 kb of genomic DNA. NF1 is caused by a loss of function mutation of the NF1 gene, a tumor suppres-sor gene, which encodes for neurofibromin, a GTPase-activating protein (GAP) involved in the negative regulation of Ras activity. The GAP-related domain, which is encoded for by exons 20-27a, is one of the most important functional domains in neurofibro-min. The cysteine-serine-rich domain has been recognized as an important functional domain in NF1-related pheochromocyto-mas. As the result of many genetic analyses of NF1-related pheochromocytomas, pheochromocytoma has generally been recog-nized as a true component of NF1. We recently experienced two families with NF1 accompanied by pheochromocytoma. The pro-band of family 1 is a 31-year-old female diagnosed with NF1 and pheochromocytoma. Gene analysis of the proband and her sister showed that the mutation of the NF1 gene (c.7907+1G>A) led to the skipping of exon 53 during NF1 mRNA splicing. The proband of family 2 is a 48-year-old male who was diagnosed with the same condition. Gene analysis demonstrated the mutation of th