Dr. Stewart joined NHGRI at the end of November 2004. The IRB approved our project in April 2005 and recruitment started shortly thereafter. By the end of fiscal 2007, we had phenotyped approximately 75 individuals affected with NF1 and collected DNA from nearly all their parents. The bench component of this project is now underway. A complementary project using large previously-banked NF1 pedigrees from Coriell Cell Repositories (Camden, NJ) and the European Collection of Cell Cultures (ECACC, Wiltshire, UK) is also underway. The purpose of this project is to determine the function of NF1 (the gene mutated in the disorder NF1) using a novel genetic and genomic method. We are preparing a manuscript detailing the results of this work. ? ? We have also developed a collaborative project (using funds from the Bench-to-Bedside program) with Dr. Brigitte Widemann and Dr. Thomas Hornyak of the National Cancer Institute to investigate the growth and biology of neurofibromas. The project, titled Natural history and biology of dermal neurofibromas in neurofibromatosis type 1 was approved by the NHGRI IRB in May 2006. It is designed to investigate the growth rate and rate of appearance of dermal neurofibromas using several imaging modalities. We will also biopsy a dermal neurofibroma and normal skin. To streamline recruiting, the eligibility criteria overlap with that of our primary project, Variation in Gene Expression in Neurofibromatosis Type 1. By the end of fiscal 2007, we were evaluating, longitudinally, the dermal neurofibromas from 12 individuals affected with NF1.? ? Since Dr. Stewart is trained as an internist, he has a special interest in manifestations of NF1 affecting adults. To this end, we have been evaluating individuals with NF1 with unique and under-recognized disease features in the adult. By the end of fiscal 2007 we had evaluated two people with NF1 and glomus tumors, which are uncommon but painful benign tumors in the fingertips. In the lab, we have made significant progress to understanding the molecular mechanism of the development of the tumors and are preparing a manuscript detailing our findings.? ? In fiscal 2007, we published in the Journal of Medical Genetics a paper on gastrointestinal stromal tumors (GISTs) in NF1 and in the journal Chest a paper on the phenotype of pulmonary arterial hypertension in NF1. We also had accepted for publication an invited review on the 9q subtelomere deletion syndrome, an uncommon chromosomal disorder Dr. Stewart described as a genetics fellow at another institution.
