NF2相关的Schwann瘤病（NF2）是由NF2基因变异引起的常染色体显性遗传疾病。约50％的NF2患者遗传致病变异，其余的则获得de novo变异。NF2的特征是双侧前庭Schwann瘤的发展。日本NF2病例的遗传背景尚未完全调查，本研究对14例日本NF2病例进行了基因分析，并检查了基因型与表型之间的相关性。采集的外周血DNA样本通过下一代测序、多重连锁依赖探针扩增分析和体外电泳进行了分析。十例患者在NF2基因中具有致病或可能致病变异，其中七个为截短变异体，三个为非截短变异体。所有七个具有截短变异体的案例的发病年龄均<20岁。具有截短NF2变异体、非截短NF2变异体和无NF2变异体的病例之间的发病年龄显著不同。然而，仅靠生殖系致病性NF2基因变异体并不能预测肿瘤生长和听力恶化的临床过程。本研究中截短变异体的频率比之前的报告更高。在分析的日本NF2病例中，基因型与年龄发病之间存在相关性。 © 2023. The Author(s).

NF2-related schwannomatosis (NF2) is an autosomal dominant genetic disorder caused by variants in the NF2 gene. Approximately 50% of NF2 patients inherit pathogenic variants, and the remainder acquire de novo variants. NF2 is characterized by development of bilateral vestibular schwannomas. The genetic background of Japanese NF2 cases has not been fully investigated, and the present report performed a genetic analysis of 14 Japanese NF2 cases and examined genotype-phenotype correlations. DNA samples collected from peripheral blood were analyzed by next-generation sequencing, multiplex ligation-dependent probe amplification analysis, and in vitro electrophoresis. Ten cases had pathogenic or likely pathogenic variants in the NF2 gene, with seven truncating variants and three non-truncating variants. The age of onset in all seven cases with truncating variants was < 20 years. The age of onset significantly differed among cases with truncating NF2 variants, non-truncating NF2 variants, and no NF2 variants. However, the clinical course of tumor growth and hearing deterioration were not predicted only by germline pathogenic NF2 variants. The rate of truncating variants was higher in the present study than that of previous reports. Genotype-phenotype correlations in the age of onset were present in the analyzed Japanese NF2 cases.© 2023. The Author(s).