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.