In the present study, we analyzed the levels of neurofibromin isoform I and II in circulating leukocytes of a cohort of genetically and clinically characterized NF1 patients stratified according to the severity of the phenotype, and correlated their expression levels with disease severity to assess whether alternative splicing may contribute to the variable expression characterizing NF1. The gene discussed is NF1; the disease is neurofibromatosis type 1.