Genetic linkage of neurofibromatosis 1 to the NF1 gene or the genetic marker in the pericentric region of chromosome 17 was established in 3 informative families.
These data implicate NF1 protein as a tumor suppressor gene product that negatively regulates p21ras and define a "positive" growth role for ras activity in NF1 malignancies.
The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase.
Defects in the NF1 gene have been implicated in the inherited disorder neurofibromatosis type 1, which is characterized by several developmental abnormalities including an increased frequency of benign and malignant tumours of neural crest origin (neurofibromas and neurofibrosarcomas respectively).
Two translocation breakpoints that interrupt the NF1 gene in NF1 patients flank a 60-kb segment of DNA that contains the EV12A locus (previously reported as the EV12 locus), the human homolog of a mouse gene, Evi-2A, implicated in retrovirus-induced murine myeloid tumors.
Linkage analysis of six Chinese families with neurofibromatosis type 1 (NF1) confirms the location of the NF1 gene to the region of the proximal long arm of chromosome 17, as in Caucasian populations.
A single-strand conformational polymorphism found in the DNA of a patient with neurofibromatosis 1 (NF1) was shown to be caused by a deletion of a CCACC or CACCT sequence and an adjacent transversion, located about 500 base pairs downstream from the region that codes for a functional domain of the NF1 gene product.
The neurofibromatosis type 1 (NF1) gene responsible for von Recklinghausen neurofibromatosis is related to regulators of ras proteins, and a portion of NF1 that is homologous to the ras GTPase-activating protein (GAP) encodes a similar GTPase-stimulating activity.
Translocation breakpoints that have been found in this region in two patients with NF1 provide physical landmarks and suggest an approach to identifying the NF1 gene.
Mapping of the EVI2 gene between the translocation breakpoints of two patients with neurofibromatosis type 1 (NF1), combined with the likely role of its murine homolog in neoplastic disease, implicates EVI2 as a possible candidate for the NF1 gene.
These observations, together with the high spontaneous mutation rate of NF1 (which is consistent with a large locus), suggest that NF1LT represents the elusive NF1 gene.
Northern blotting identified mouse NF-1 transcripts that are equivalent in size and complexity to those in human tissues, and Southern blotting shows that this region of the NF-1 gene is evolutionarily well conserved.
The breakpoint in chromosome 17 is cytogenetically identical to a previously reported case of NF1 associated with a 1;17 balanced translocation and suggests that the translocation events disrupt the NF1 gene.
NF1 did not recombine with either TH17.19 or HHH202 in any of the informative meioses surveyed (maximum lod scores of 17.04 and 7.21, respectively, at a recombination fraction of .00), indicating that these markers map very close to the NF1 gene.