Abstract：
OBJECTIVE: Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.
METHODS: We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).
RESULTS: Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (\"first hit\") but distinct \"second hit\" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.
CONCLUSIONS: Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.
METHODS: We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).
RESULTS: Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (\"first hit\") but distinct \"second hit\" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.
CONCLUSIONS: Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.
摘要：
目的：区分散发性和种系/马赛克NF2相关神经鞘瘤病对于确保患者获得适当的长期护理很重要。有了这份报告,我们描述了一例4例同侧神经鞘瘤患者的独特病例,并确定了可以准确诊断镶嵌型NF2相关神经鞘瘤病的测序方式组合.
方法：我们介绍了一位32岁的女性，她的父亲有前庭神经鞘瘤家族史，右侧神经鞘瘤累及耳蜗的顶端和基底转向，外侧半规管，和内耳道（IAC）。使用下一代测序（NGS）对2种肿瘤（abyrinethine和IAC肿瘤）的血液和冷冻组织进行遗传分析，多重连接依赖性探针扩增（MLPA），和光学基因组作图(OGM)。
结果：NF2、LZTR1和SMARCB1的胚系检测结果为阴性。肿瘤基因检测揭示了两种肿瘤之间共有的NF2致病变异（“第一次击中”），但明显的“第二次击中”NF2变异，包括仅使用OGM观察到的IAC肿瘤中22号染色体的马赛克丢失，与马赛克NF2相关的神经鞘瘤病一致。
结论：多模态测序，包括NGS,MLPA，和OGM,需要确保该患者的马赛克NF2相关神经鞘瘤病的适当诊断。类似的方法可用于患有多个同侧肿瘤和可疑肿瘤倾向的其他患者。
方法：我们介绍了一位32岁的女性，她的父亲有前庭神经鞘瘤家族史，右侧神经鞘瘤累及耳蜗的顶端和基底转向，外侧半规管，和内耳道（IAC）。使用下一代测序（NGS）对2种肿瘤（abyrinethine和IAC肿瘤）的血液和冷冻组织进行遗传分析，多重连接依赖性探针扩增（MLPA），和光学基因组作图(OGM)。
结果：NF2、LZTR1和SMARCB1的胚系检测结果为阴性。肿瘤基因检测揭示了两种肿瘤之间共有的NF2致病变异（“第一次击中”），但明显的“第二次击中”NF2变异，包括仅使用OGM观察到的IAC肿瘤中22号染色体的马赛克丢失，与马赛克NF2相关的神经鞘瘤病一致。
结论：多模态测序，包括NGS,MLPA，和OGM,需要确保该患者的马赛克NF2相关神经鞘瘤病的适当诊断。类似的方法可用于患有多个同侧肿瘤和可疑肿瘤倾向的其他患者。
