Abstract

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized primarily by the development of multiple neurofibromas and pigmentary changes. The recent identification of contiguous gene deletions in NF1, a previously unrecognized molecular basis for this disorder, raises important questions regarding deletion frequency in the patient population and the role that contiguous genes may play in the physical manifestations of NF1 patients. To facilitate the identification of patients with large NF1 deletions, we have isolated clones carrying large genomic segments from the NF1 locus and tested their efficacy as probes for fluorescence in situ hybridization (FISH). Clone P1-9 spans approximately 65 kb of the NF1 gene, including exons 2-11, and clone P1-12 carries approximately 55 kb of NF1 intron 27B. FISH studies performed with P1-9, P1-12, and a set of overlapping 1F10 cosmid clones mapping telomeric to the NF1 locus identified large deletions in two new neurofibromatosis type 1 patients who, like previously characterized deletion patients, had mildly dysmorphic facial features and large numbers of cutaneous neurofibromas.