Neurofibromatosis 2 phenotypes and germ-line NF2 mutations determined by an RNA mismatch method and loss of heterozygosity analysis in NF2 schwannomas

We used a novel RNase cleavage assay (NIRCA) to screen for neurofibromatosi s 2 (NF2) mutations in NF2 schwannomas. Mutations were found in tumors in 1 6 of 20 patients. Eleven patients (55%) had loss of heterozygosity or loss of one allele, indicating that the mutation was a germ-line mutation. The p henotypes of these patients were consistent with previous NF2 genotype-phen otype correlation studies: patients with nonsense mutations had severe phen otypes, whereas those with splice-site or missense mutations had milder and variable phenotypes. These results confirm the utility of NIRCA as a rapid and convenient method for screening for germ-line NF2 mutations. (C) Elsev ier Science Inc., 2000. All rights reserved.