title: Further genotype--phenotype correlations in neurofibromatosis 2.
abstract: Neurofibromatosis 2 (NF2) is caused by mutations in the NF2 gene predisposing carriers to develop nervous system tumours. Different NF2 mutations result in either loss/reduced protein function or gain of protein function (abnormally behaving mutant allele i.e. truncated protein potentially causing dominant negative effect). We present a comparison between the clinical presentations of patients with mutations that are predicted to produce truncated protein (nonsense/frameshift mutations) to those that results in loss of protein expression (large deletions) to elucidate further genotype-phenotype correlations in NF2. Patients with nonsense/frameshift mutations have a younger age of diagnosis and a higher prevalence/proportion of meningiomas (p = 0.002, p = 0.014), spinal tumours (p = 0.004, p = 0.004) and non-VIII cranial nerve tumours (p = 0.006, p = 0.003). We also found younger age of diagnosis of vestibular schwannomas (p = 0.007), higher mean numbers of cutaneous lesions (p = 0.003) and spinal tumours (p = 0.006) in these patients. With respect to NF2 symptoms, we found younger age of onset of hearing loss (p = 0.010), tinnitus (p = 0.002), paraesthesiae (p = 0.073), wasting and weakness (p = 0.001) and headaches (p = 0.049) in patients with nonsense/frameshift mutations. Our comparison shows, additional, new correlations between mutations in the NF2 gene and the NF2 disease phenotype, and this further confirms that nonsense/frameshift mutations are associated with more severe NF2 symptoms. Therefore patients with this class of NF2 mutation should be followed up closely.
authors.affiliation: Department of Genetics, St Mary's Hospital, Manchester, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Selvanathan
authors.forename: A
authors.initials: A
authors.lastname: Shenton
authors.forename: R
authors.initials: R
authors.lastname: Ferner
authors.forename: A J
authors.initials: AJ
authors.lastname: Wallace
authors.forename: S M
authors.initials: SM
authors.lastname: Huson
authors.forename: R T
authors.initials: RT
authors.lastname: Ramsden
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D016515:Genes, Neurofibromatosis 2; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D016518:Neurofibromatosis 2 / Q000235:genetics*; D010641:Phenotype
chemical_list: D005819:Genetic Markers