NF1 gene and neurofibromatosis 1

Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant condition caused by mutations of the NF1 gene, which is located at chromosome 17q11.2, NF1 is believed to be completely penetrant, but substantial variability in expression of features occurs. Diagnosis of NF1 is based on established clinical criteria. The presentation of many of the clinical features is age dependent. The average life expectancy of pati ents with NF1 is probably reduced by 10-15 years, and malignancy is the mos t common cause of death. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies, A wide variety of NF1 mutations has been found in patients with NF1, but no frequently recur ring mutation has been identified. Most studies have not found an obvious r elation between particular NF1 mutations and the resulting clinical manifes tations. The variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests that other factors are involved in determ ining the clinical manifestations, but the nature of these factors has not yet been determined. Laboratory testing for NF1 mutations is difficult. A p rotein truncation test is commercially available, but its sensitivity, spec ificity, and predictive value have not been established, No general, popula tion-based molecular studies of NF1 mutations have been performed. At this time, it appears that the benefits of population-based screening for clinic al features of NF1 would not outweigh the costs of screening.