Clinical and Molecular Consequences of NF1 Microdeletion

摘要

Previous work included development of sensitive assays for the detection and mapping of both the common 1.4 Mb NF1 microdeletion and novel microdeletions. Collaborations involving this work led to several key publications in prior years. Work subcontracted to Dr. Wallace at the University of Florida included screening for mutations in putative modifiers RAB11FIP4 and JJAZ1 (SUZ12) (in the microdeletion region), which found some novel JJAZ1 variants but nothing obviously functionally abnormal, in microdeletion patients and in non-deletion patients with heavy tumor loads. Thus, we have no evidence that these flanking genes modify the NF1 phenotype. No microsatellite instability was found in tumors from microdeletion patients (or some others from non-deletion patients). Several 2nd hits were found in tumors of microdeletion patients, with none being a large deletion (two nonsense, and one in-frame 3 bp deletion). The new specific aim, immortalization of Schwann cell cultures from neurofibromas, was successful, establishing the world's first immortalized normal human Schwann cell line and three Schwann cell lines from neurofibromas.