BIOM-47. SINGLE NUCLEOTIDE POLYMORPHISM IN SMARCB1 MUTATION FOR SCHWANNOMATOSIS

Abstract Schwannomatosis, a form of neurofibromatosis, involves critical roles for the SMARCB1 gene. Clinical diagnosis guidelines recommend considering pathogenic variants or suspecting schwannomatosis to exclude splicing-related intron mutations. However, some patients may initially present with non-significant mutations and lack clinical signs of schwannoma, leading to misdiagnosis, missed annual assessments, malignancy awareness, and genetic consultation opportunities during pregnancy. Here, we reported a patient with a sporadic synonymous mutation in the SMARCB1 gene (SNP c.1032 C>T (p.Gly344Gly(GGC>GGT)) in exon 8), not previously associated with schwannomatosis. This patient, a 55-year-old female with an 8-year history of schwannomatosis, presented to the neurosurgical department for recurrent tumor removal. Initially, the clinical impact of the SMARCB1 mutation was undetermined, and other genes tested were wild-type. Both schwannomas exhibited a mosaic loss of nuclear SMARCB1 protein, ranging from 10% to 60%. Protein assays confirmed low levels of SMARCB1 protein, with a significant loss in the distal thigh schwannoma. It highlights the tumorigenic potential of single nucleotide polymorphism in the SMARCB1 gene and aids clinicians in making more accurate diagnoses in patients with pathologically confirmed schwannoma. It underscores the importance of long-term follow-up, increased awareness of recurrence and malignancy, and timely surgical planning in such patients.