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Mapping the Somatic Mutation Landscape of Familial NF2-Related Schwannomatosis using Whole-Exome Sequencing

Year: 2025

Type: article

Abstract: Background: Neurofibromatosis type 2 (NF2), currently more accurately named NF2-related schwannomatosis (NF2-SWN), is classified as a multiple tumor syndrome, caused by impaired expression of the merlin protein.Approximately 50% of affected individuals inherit a germline mutation from their parents, while reports on the somatic mutation landscape of other genes are infrequent.Aim: To further explore the somatic mutations of NF2-SWN and provide a theoretical basis for the treatment of NF2-SWN.Design: A retrospective study was conducted to follow up on NF2-SWN patients who underwent surgical treatment in the Department of Neurosurgery of Xiangya Hospital.Whole-exome sequencing (WES) was performed on patients with a clear family history.Methods: This study compiled clinical data from 29 patients diagnosed with NF2-SWN, conducted WES on 7 patients with well-documented genetic histories, and subsequently analyzed their genetic mutations.Results: Whole-exome sequencing identified frequent somatic mutations in genes such as TTN, FLG, CR2, and FSIP2.Missense mutations and C>T transitions were the most common alteration types.Conclusion: TTN, CR2, FLG, and FSIP2 demonstrated elevated mutation frequencies in these familial NF2-SWN patients, indicating that these mutations may contribute to the development and progression of familial NF2-SWN.

Source: International Journal of Medical Sciences

DOI: 10.7150/ijms.121550