Neurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in the NF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the presence of schwannomas, meningiomas and ependymomas. Here we report the presence of NF2 in one twin, with bilateral vestibular schwannomas and a pathogenic variant of the NF2 gene identified in both tumour and lymphocytes, while his monozygous brother remains asymptomatic. Imaging of the unaffected twin showed no tumour load and genetic testing via Sanger sequencing and Amplification Refractory Mutation System assay demonstrated low levels of expression of the NF2 variant in lymphocytes. Further testing on non-haemopoietic tissue showed little expression or absence of the pathogenic variant. Given there is no family history and the low level of the variant, we assume the pathogenic variant is a de novo mutation during embryogenesis. De novo mutations have been described as occurring at three possible time points in the creation of monozygous twins with different genetic make-up; prior to the twinning event, as a cause of the event, or after the twinning event. Of these options, we hypothesise that the discordance in the expression of the NF2 variant between these twins is likely due to a mutational event that occurred as a result of either of the latter two possibilities, between which we cannot determine. The pathogenic variant in lymphocytes was likely transferred between the twins through a shared blood supply in utero, and the non-haemopoietic samples that showed low levels of expression, were likely due to the presence of lymphocytic cells. Therefore, we have a discordance between monozygous twins at the NF2 gene.

中文翻译：

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单卵双胞胎的2型神经纤维瘤病不一致。

2型神经纤维瘤病（NF2）是由NF2基因的致病变异引起的常染色体显性疾病。该病原体是通过遗传突变或通过从头突变获得的，其特征在于存在神经鞘瘤，脑膜瘤和室管膜瘤。在这里，我们报告在一个双胞胎中存在NF2，伴有双侧前庭神经鞘瘤和NF2的致病变异该基因在肿瘤和淋巴细胞中均被发现，而他的单卵菌兄弟仍无症状。未患病的双胞胎的成像显示无肿瘤负荷，并且通过Sanger测序和扩增难治性突变系统测定的遗传测试表明淋巴细胞中NF2变体的表达水平较低。在非造血组织上进行的进一步测试显示，病原体变体很少表达或不存在。鉴于没有家族史且变异水平较低，我们假设致病变异是胚胎发生过程中的从头突变。从头突变被描述为在具有不同遗传组成的单卵双胞胎的创建中的三个可能的时间点发生。在孪生事件之前，作为事件的原因或在孪生事件之后。在这些选项中，这些双胞胎之间的NF2变异可能是由于后两种可能性之一而发生的突变事件造成的，我们无法确定这两种可能性之间的差异。淋巴细胞中的致病变异可能是通过子宫内共享的血液供应在双胞胎之间转移的，而表达水平较低的非造血样本可能是由于淋巴细胞的存在所致。因此，我们在NF2基因的单卵双胞胎之间存在分歧。