NF2 genetic alterations in sporadic vestibular schwannomas: Clinical implications

Luis Lassaletta, Miguel Torres-Martín, Carolina Peña-Granero, Jose Maria Roda, Santiago Santa-Cruz-Ruiz, Javier S. Castresana, Javier Gavilan, Juan A. Rey

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Hypothesis: NF2 gene alterations may have a clinical impact in non-NF2 vestibular schwannomas (VSs). Background: It has been suggested that NF2 mutations might correlate with clinical expression of VS in NF2 patients. The aim of this study was to analyze the impact of genetic alterations in the NF2 gene on epidemiologic, clinical, and radiologic features of patients with sporadic VS. The association between cigarette consumption and the molecular genetic findings was also studied. Methods: The study group consisted of 51 patients who underwent surgery for removal of vestibular schwannoma in our institution between January 2006 and December 2010. Five highly polymorphic microsatellite DNA markers were used to observe the frequency of loss of heterozygosity (LOH) in chromosome 22. The NF2 gene mutations were detected using polymerase chain reaction amplification and denaturing high-performance liquid chromatography analysis (PCR/dHPLC), and direct sequencing of NF2. Multiplex ligation-dependent probe amplification (MLPA) of the NF2 gene was also performed. Results: An NF2 mutation was identified in 49%, 22q LOH in 57%, and MLPA alterations in 13.7% of the cases. One mutational hit was present in 27%, and 2 hits were present in 45% of the tumors. No association was found between the type of NF2 mutation and relevant clinical parameters. The presence of NF2 mutations detected by PCR/dHPLC was associated with no complaint of hearing loss at the time of diagnosis (p = 0.023), with subjective aural fullness (p = 0.022) and with an absence of tumor involvement of the internal auditory canal (p = 0.029). Patients with NF2 mutations had lower mean corrected PTA thresholds compared with those with no NF2 mutation (p = 0.037). Inactivation of the NF2 gene by mutation, MLPA, or LOH was more frequent in smokers when compared with never smokers (p = 0.048). Conclusion: NF2 mutations may play a role in the pathophysiology of hearing loss as well as in the pattern of growth of VS. Cigarette smoking in patients with VS seems to play a role in both the risk of developing the tumor and also in its genetic profile. More studies are needed to corroborate these results and, more broadly, to establish links between molecular and clinical data.

Original languageEnglish
Pages (from-to)1355-1361
Number of pages7
JournalOtology and Neurotology
Issue number7
StatePublished - Sep 2013
Externally publishedYes


  • Clinical implications
  • Hearing loss
  • NF2 gene
  • NF2 mutation
  • Vestibular schwannoma


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