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

<b>Background:</b> Neurofibromatosis type 2 (NF2), currently more accurately named <i>NF2</i>-related schwannomatosis (<i>NF2-</i>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. <b>Aim:</b> To further explore the somatic mutations of <i>NF2-</i>SWN and provide a theoretical basis for the treatment of <i>NF2-</i>SWN. <b>Design:</b> A retrospective study was conducted to follow up on <i>NF2-</i>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. <b>Methods:</b> This study compiled clinical data from 29 patients diagnosed with <i>NF2-</i>SWN, conducted WES on 7 patients with well-documented genetic histories, and subsequently analyzed their genetic mutations. <b>Results:</b> 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. <b>Conclusion:</b> TTN, CR2, FLG, and FSIP2 demonstrated elevated mutation frequencies in these familial <i>NF2-</i>SWN patients, indicating that these mutations may contribute to the development and progression of familial <i>NF2-</i>SWN.