GERMLINE MUTATIONS IN THE NEUROFIBROMATOSIS TYPE-2 TUMOR-SUPPRESSOR GENE

The recent identification of the NF2 tumour suppressor gene has enable d large scale screening for pathological mutations in the gene. We hav e sought germline mutations in the NF2 gene by SSCP and heteroduplex a nalysis of cDNA and genomic DNA samples followed by cloning and sequen cing of mutant alleles. In the present report we describe 11 putative pathological mutations, including five nonsense mutations, three short insertions or deletions causing frameshifts and three missense mutati ons. Mast stop mutations and frameshift mutations were found in indivi duals expressing a severe phenotype while one of the three missense mu tations was associated with a mild phenotype. Four unrelated NF2 patie nts of the 93 tested were found to have identical nonsense mutations c aused by a C to T transition (C169) in a CpG dinucleotide, which is a potential mutational hotspot in the NF2 tumour suppressor gene.