It encodes a large GAP- related protein called neurofibromin. The gene has a high mutation rate, as evidenced by the fact that about half of all newly-diagnosed cases do not have a prior family history of NF1. We have DNA and leukocyte RNA samples from over 200 individuals with NF1 and are analyzing these for germline NF1 gene mutations and examining several aspects of genetics in the inheritance and expression of this disorder. For example, we recently identified the first case of somatic mosaicism in NF1, which may be a common mechanism in the occurrence of new mutation cases. The symptoms can be relatively mild, or there can be such serious malformations that the child dies in infancy.
Mental retardation is inevitable.
Although a biochemical defect has been identified, the molecular genetic basis has not been defined. We are using positional cloning techniques to map and clone the translocation breakpoint, in concert with linkage analysis to indicate whether other genomic regions may contain related genes. The ultimate test of candidate genes is to identify mutations in SLOS patients. SVAS is caused by a defective or missing elastin gene, and we are searching for mutations in several families. Elastin region deletions in Williams syndrome.