title: The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene.
abstract: Constitutional heterozygous inactivating mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene cause the autosomal dominant disease NF2, and biallelic inactivating somatic NF2 mutations are found in a high proportion of unilateral sporadic vestibular schwannoma (USVS) and sporadic meningioma. We surveyed the distributions of constitutional NF2 mutations in 823 NF2 families, 278 somatic NF2 mutations in USVS, and 208 somatic NF2 mutations in sporadic meningioma. Based on the available NF2 mutation data, the most dominant influence on the spectra of mutations in exons 1-15 are C>T transitions that change arginine codons (CGA) to stop codons (TGA) due to spontaneous deamination of methylcytosine to thymine in CpG dinucleotides. The paucity of reported mutations in exon 9 and the absence of reported mutations in exons 16 and 17 may be related to structure-function relationships in the NF2 protein.
authors.affiliation: Academic Unit of Medical Genetics, St. Mary's Hospital, Manchester, United Kingdom.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Baser
mesh_terms: D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D008958:Models, Molecular; D016518:Neurofibromatosis 2 / Q000235:genetics*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D018389:Codon, Nonsense