Gene mutation at chromosome 22 in sporadic patients with spinal schwannomatosis: A preliminary analysis

Abstract

Objective To analyze the correlation on the prominent germline or somatic mutations at chromosome 22 of the sporadic patients with spinal schwannomatosis. Methods From May to November 2015, 9 serial patients with multiple spinal cord tumors underwent open surgery at Neurosurgical Department, the Third Hospital of Peking University. All spinal cord tumors in the 9 patients were removed by operation. The multiple spinal cord tumors were located at lumbar segments in 4 patients, at cervical segments in 4, and at thoracolumbar segments in 1. The samples of tumor and blood were preserved during operation. In order to determine the SNP (single nucleotide polymorphism), SNV (single nucleotide variants) and CNV (copy number variations) of 9 patients, whole-exome targeted enrichment and sequencing were performed on tumor and blood DNA after operation. Results The open surgery was successful performed in 9 patients. Among 9 patients, histological staining showed neurofibromatosis type I (NF1) in 3 cases, ganglioneuroma in 1, ependymoma in 1, and schwannomatosis in 4 (1 case with comorbidity of bilateral acoustic tumors). Among 9 sporadic cases, gene mutation was detected in a large region of chromosome 22 only in 4 cases with spinal schwannomatosis. Among 4 cases, the germline mutation was identified in 2 cases, and somatic mutation in 2 cases. Splice-donor neurofibromatosis type 2 (NF2) germline high frequency mutation (T→C) was identified in the No.1 patient. Frame-shift leucine-zipper-like transcriptional regulator 1 (LZTR1) germline high frequency mutation (G→GT) was identified in the No. 2 patient. Frameshift NF2 somatic mutation (CGA→C) was identified in the No. 3 patient. Stop-gained NF2 somatic mutation was identified in the No. 4 patient. Among 4 cases, chromosome fibrillin 3 (FBN3) intermediate frequency missense mutation was simultaneously found in chromosome 19 in 2 cases, out of which 1 was somatic mutation and the other was germ line mutation. Conclusion The preliminary results have suggested that most of the genes with high frequency mutations in spinal schwannomatosis are on chromosome 22. Key words: Schwannomatosis; Spinal cord; Genetic testing